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OBG Management is a leading publication in the ObGyn specialty addressing patient care and practice management under one cover.
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
Islamic caliphate
Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
nsfw
pedophile
pedophilia
poker
porn
pornography
psychedelic drug
recreational drug
sex slave rings
slot machine
terrorism
terrorist
Texas hold 'em
UFC
substance abuse
abuseed
abuseer
abusees
abuseing
abusely
abuses
aeolus
aeolused
aeoluser
aeoluses
aeolusing
aeolusly
aeoluss
ahole
aholeed
aholeer
aholees
aholeing
aholely
aholes
alcohol
alcoholed
alcoholer
alcoholes
alcoholing
alcoholly
alcohols
allman
allmaned
allmaner
allmanes
allmaning
allmanly
allmans
alted
altes
alting
altly
alts
analed
analer
anales
analing
anally
analprobe
analprobeed
analprobeer
analprobees
analprobeing
analprobely
analprobes
anals
anilingus
anilingused
anilinguser
anilinguses
anilingusing
anilingusly
anilinguss
anus
anused
anuser
anuses
anusing
anusly
anuss
areola
areolaed
areolaer
areolaes
areolaing
areolaly
areolas
areole
areoleed
areoleer
areolees
areoleing
areolely
areoles
arian
arianed
arianer
arianes
arianing
arianly
arians
aryan
aryaned
aryaner
aryanes
aryaning
aryanly
aryans
asiaed
asiaer
asiaes
asiaing
asialy
asias
ass
ass hole
ass lick
ass licked
ass licker
ass lickes
ass licking
ass lickly
ass licks
assbang
assbanged
assbangeded
assbangeder
assbangedes
assbangeding
assbangedly
assbangeds
assbanger
assbanges
assbanging
assbangly
assbangs
assbangsed
assbangser
assbangses
assbangsing
assbangsly
assbangss
assed
asser
asses
assesed
asseser
asseses
assesing
assesly
assess
assfuck
assfucked
assfucker
assfuckered
assfuckerer
assfuckeres
assfuckering
assfuckerly
assfuckers
assfuckes
assfucking
assfuckly
assfucks
asshat
asshated
asshater
asshates
asshating
asshatly
asshats
assholeed
assholeer
assholees
assholeing
assholely
assholes
assholesed
assholeser
assholeses
assholesing
assholesly
assholess
assing
assly
assmaster
assmastered
assmasterer
assmasteres
assmastering
assmasterly
assmasters
assmunch
assmunched
assmuncher
assmunches
assmunching
assmunchly
assmunchs
asss
asswipe
asswipeed
asswipeer
asswipees
asswipeing
asswipely
asswipes
asswipesed
asswipeser
asswipeses
asswipesing
asswipesly
asswipess
azz
azzed
azzer
azzes
azzing
azzly
azzs
babeed
babeer
babees
babeing
babely
babes
babesed
babeser
babeses
babesing
babesly
babess
ballsac
ballsaced
ballsacer
ballsaces
ballsacing
ballsack
ballsacked
ballsacker
ballsackes
ballsacking
ballsackly
ballsacks
ballsacly
ballsacs
ballsed
ballser
ballses
ballsing
ballsly
ballss
barf
barfed
barfer
barfes
barfing
barfly
barfs
bastard
bastarded
bastarder
bastardes
bastarding
bastardly
bastards
bastardsed
bastardser
bastardses
bastardsing
bastardsly
bastardss
bawdy
bawdyed
bawdyer
bawdyes
bawdying
bawdyly
bawdys
beaner
beanered
beanerer
beaneres
beanering
beanerly
beaners
beardedclam
beardedclamed
beardedclamer
beardedclames
beardedclaming
beardedclamly
beardedclams
beastiality
beastialityed
beastialityer
beastialityes
beastialitying
beastialityly
beastialitys
beatch
beatched
beatcher
beatches
beatching
beatchly
beatchs
beater
beatered
beaterer
beateres
beatering
beaterly
beaters
beered
beerer
beeres
beering
beerly
beeyotch
beeyotched
beeyotcher
beeyotches
beeyotching
beeyotchly
beeyotchs
beotch
beotched
beotcher
beotches
beotching
beotchly
beotchs
biatch
biatched
biatcher
biatches
biatching
biatchly
biatchs
big tits
big titsed
big titser
big titses
big titsing
big titsly
big titss
bigtits
bigtitsed
bigtitser
bigtitses
bigtitsing
bigtitsly
bigtitss
bimbo
bimboed
bimboer
bimboes
bimboing
bimboly
bimbos
bisexualed
bisexualer
bisexuales
bisexualing
bisexually
bisexuals
bitch
bitched
bitcheded
bitcheder
bitchedes
bitcheding
bitchedly
bitcheds
bitcher
bitches
bitchesed
bitcheser
bitcheses
bitchesing
bitchesly
bitchess
bitching
bitchly
bitchs
bitchy
bitchyed
bitchyer
bitchyes
bitchying
bitchyly
bitchys
bleached
bleacher
bleaches
bleaching
bleachly
bleachs
blow job
blow jobed
blow jober
blow jobes
blow jobing
blow jobly
blow jobs
blowed
blower
blowes
blowing
blowjob
blowjobed
blowjober
blowjobes
blowjobing
blowjobly
blowjobs
blowjobsed
blowjobser
blowjobses
blowjobsing
blowjobsly
blowjobss
blowly
blows
boink
boinked
boinker
boinkes
boinking
boinkly
boinks
bollock
bollocked
bollocker
bollockes
bollocking
bollockly
bollocks
bollocksed
bollockser
bollockses
bollocksing
bollocksly
bollockss
bollok
bolloked
bolloker
bollokes
bolloking
bollokly
bolloks
boner
bonered
bonerer
boneres
bonering
bonerly
boners
bonersed
bonerser
bonerses
bonersing
bonersly
bonerss
bong
bonged
bonger
bonges
bonging
bongly
bongs
boob
boobed
boober
boobes
boobies
boobiesed
boobieser
boobieses
boobiesing
boobiesly
boobiess
boobing
boobly
boobs
boobsed
boobser
boobses
boobsing
boobsly
boobss
booby
boobyed
boobyer
boobyes
boobying
boobyly
boobys
booger
boogered
boogerer
boogeres
boogering
boogerly
boogers
bookie
bookieed
bookieer
bookiees
bookieing
bookiely
bookies
bootee
booteeed
booteeer
booteees
booteeing
booteely
bootees
bootie
bootieed
bootieer
bootiees
bootieing
bootiely
booties
booty
bootyed
bootyer
bootyes
bootying
bootyly
bootys
boozeed
boozeer
boozees
boozeing
boozely
boozer
boozered
boozerer
boozeres
boozering
boozerly
boozers
boozes
boozy
boozyed
boozyer
boozyes
boozying
boozyly
boozys
bosomed
bosomer
bosomes
bosoming
bosomly
bosoms
bosomy
bosomyed
bosomyer
bosomyes
bosomying
bosomyly
bosomys
bugger
buggered
buggerer
buggeres
buggering
buggerly
buggers
bukkake
bukkakeed
bukkakeer
bukkakees
bukkakeing
bukkakely
bukkakes
bull shit
bull shited
bull shiter
bull shites
bull shiting
bull shitly
bull shits
bullshit
bullshited
bullshiter
bullshites
bullshiting
bullshitly
bullshits
bullshitsed
bullshitser
bullshitses
bullshitsing
bullshitsly
bullshitss
bullshitted
bullshitteded
bullshitteder
bullshittedes
bullshitteding
bullshittedly
bullshitteds
bullturds
bullturdsed
bullturdser
bullturdses
bullturdsing
bullturdsly
bullturdss
bung
bunged
bunger
bunges
bunging
bungly
bungs
busty
bustyed
bustyer
bustyes
bustying
bustyly
bustys
butt
butt fuck
butt fucked
butt fucker
butt fuckes
butt fucking
butt fuckly
butt fucks
butted
buttes
buttfuck
buttfucked
buttfucker
buttfuckered
buttfuckerer
buttfuckeres
buttfuckering
buttfuckerly
buttfuckers
buttfuckes
buttfucking
buttfuckly
buttfucks
butting
buttly
buttplug
buttpluged
buttpluger
buttpluges
buttpluging
buttplugly
buttplugs
butts
caca
cacaed
cacaer
cacaes
cacaing
cacaly
cacas
cahone
cahoneed
cahoneer
cahonees
cahoneing
cahonely
cahones
cameltoe
cameltoeed
cameltoeer
cameltoees
cameltoeing
cameltoely
cameltoes
carpetmuncher
carpetmunchered
carpetmuncherer
carpetmuncheres
carpetmunchering
carpetmuncherly
carpetmunchers
cawk
cawked
cawker
cawkes
cawking
cawkly
cawks
chinc
chinced
chincer
chinces
chincing
chincly
chincs
chincsed
chincser
chincses
chincsing
chincsly
chincss
chink
chinked
chinker
chinkes
chinking
chinkly
chinks
chode
chodeed
chodeer
chodees
chodeing
chodely
chodes
chodesed
chodeser
chodeses
chodesing
chodesly
chodess
clit
clited
cliter
clites
cliting
clitly
clitoris
clitorised
clitoriser
clitorises
clitorising
clitorisly
clitoriss
clitorus
clitorused
clitoruser
clitoruses
clitorusing
clitorusly
clitoruss
clits
clitsed
clitser
clitses
clitsing
clitsly
clitss
clitty
clittyed
clittyer
clittyes
clittying
clittyly
clittys
cocain
cocaine
cocained
cocaineed
cocaineer
cocainees
cocaineing
cocainely
cocainer
cocaines
cocaining
cocainly
cocains
cock
cock sucker
cock suckered
cock suckerer
cock suckeres
cock suckering
cock suckerly
cock suckers
cockblock
cockblocked
cockblocker
cockblockes
cockblocking
cockblockly
cockblocks
cocked
cocker
cockes
cockholster
cockholstered
cockholsterer
cockholsteres
cockholstering
cockholsterly
cockholsters
cocking
cockknocker
cockknockered
cockknockerer
cockknockeres
cockknockering
cockknockerly
cockknockers
cockly
cocks
cocksed
cockser
cockses
cocksing
cocksly
cocksmoker
cocksmokered
cocksmokerer
cocksmokeres
cocksmokering
cocksmokerly
cocksmokers
cockss
cocksucker
cocksuckered
cocksuckerer
cocksuckeres
cocksuckering
cocksuckerly
cocksuckers
coital
coitaled
coitaler
coitales
coitaling
coitally
coitals
commie
commieed
commieer
commiees
commieing
commiely
commies
condomed
condomer
condomes
condoming
condomly
condoms
coon
cooned
cooner
coones
cooning
coonly
coons
coonsed
coonser
coonses
coonsing
coonsly
coonss
corksucker
corksuckered
corksuckerer
corksuckeres
corksuckering
corksuckerly
corksuckers
cracked
crackwhore
crackwhoreed
crackwhoreer
crackwhorees
crackwhoreing
crackwhorely
crackwhores
crap
craped
craper
crapes
craping
craply
crappy
crappyed
crappyer
crappyes
crappying
crappyly
crappys
cum
cumed
cumer
cumes
cuming
cumly
cummin
cummined
cumminer
cummines
cumming
cumminged
cumminger
cumminges
cumminging
cummingly
cummings
cummining
cumminly
cummins
cums
cumshot
cumshoted
cumshoter
cumshotes
cumshoting
cumshotly
cumshots
cumshotsed
cumshotser
cumshotses
cumshotsing
cumshotsly
cumshotss
cumslut
cumsluted
cumsluter
cumslutes
cumsluting
cumslutly
cumsluts
cumstain
cumstained
cumstainer
cumstaines
cumstaining
cumstainly
cumstains
cunilingus
cunilingused
cunilinguser
cunilinguses
cunilingusing
cunilingusly
cunilinguss
cunnilingus
cunnilingused
cunnilinguser
cunnilinguses
cunnilingusing
cunnilingusly
cunnilinguss
cunny
cunnyed
cunnyer
cunnyes
cunnying
cunnyly
cunnys
cunt
cunted
cunter
cuntes
cuntface
cuntfaceed
cuntfaceer
cuntfacees
cuntfaceing
cuntfacely
cuntfaces
cunthunter
cunthuntered
cunthunterer
cunthunteres
cunthuntering
cunthunterly
cunthunters
cunting
cuntlick
cuntlicked
cuntlicker
cuntlickered
cuntlickerer
cuntlickeres
cuntlickering
cuntlickerly
cuntlickers
cuntlickes
cuntlicking
cuntlickly
cuntlicks
cuntly
cunts
cuntsed
cuntser
cuntses
cuntsing
cuntsly
cuntss
dago
dagoed
dagoer
dagoes
dagoing
dagoly
dagos
dagosed
dagoser
dagoses
dagosing
dagosly
dagoss
dammit
dammited
dammiter
dammites
dammiting
dammitly
dammits
damn
damned
damneded
damneder
damnedes
damneding
damnedly
damneds
damner
damnes
damning
damnit
damnited
damniter
damnites
damniting
damnitly
damnits
damnly
damns
dick
dickbag
dickbaged
dickbager
dickbages
dickbaging
dickbagly
dickbags
dickdipper
dickdippered
dickdipperer
dickdipperes
dickdippering
dickdipperly
dickdippers
dicked
dicker
dickes
dickface
dickfaceed
dickfaceer
dickfacees
dickfaceing
dickfacely
dickfaces
dickflipper
dickflippered
dickflipperer
dickflipperes
dickflippering
dickflipperly
dickflippers
dickhead
dickheaded
dickheader
dickheades
dickheading
dickheadly
dickheads
dickheadsed
dickheadser
dickheadses
dickheadsing
dickheadsly
dickheadss
dicking
dickish
dickished
dickisher
dickishes
dickishing
dickishly
dickishs
dickly
dickripper
dickrippered
dickripperer
dickripperes
dickrippering
dickripperly
dickrippers
dicks
dicksipper
dicksippered
dicksipperer
dicksipperes
dicksippering
dicksipperly
dicksippers
dickweed
dickweeded
dickweeder
dickweedes
dickweeding
dickweedly
dickweeds
dickwhipper
dickwhippered
dickwhipperer
dickwhipperes
dickwhippering
dickwhipperly
dickwhippers
dickzipper
dickzippered
dickzipperer
dickzipperes
dickzippering
dickzipperly
dickzippers
diddle
diddleed
diddleer
diddlees
diddleing
diddlely
diddles
dike
dikeed
dikeer
dikees
dikeing
dikely
dikes
dildo
dildoed
dildoer
dildoes
dildoing
dildoly
dildos
dildosed
dildoser
dildoses
dildosing
dildosly
dildoss
diligaf
diligafed
diligafer
diligafes
diligafing
diligafly
diligafs
dillweed
dillweeded
dillweeder
dillweedes
dillweeding
dillweedly
dillweeds
dimwit
dimwited
dimwiter
dimwites
dimwiting
dimwitly
dimwits
dingle
dingleed
dingleer
dinglees
dingleing
dinglely
dingles
dipship
dipshiped
dipshiper
dipshipes
dipshiping
dipshiply
dipships
dizzyed
dizzyer
dizzyes
dizzying
dizzyly
dizzys
doggiestyleed
doggiestyleer
doggiestylees
doggiestyleing
doggiestylely
doggiestyles
doggystyleed
doggystyleer
doggystylees
doggystyleing
doggystylely
doggystyles
dong
donged
donger
donges
donging
dongly
dongs
doofus
doofused
doofuser
doofuses
doofusing
doofusly
doofuss
doosh
dooshed
doosher
dooshes
dooshing
dooshly
dooshs
dopeyed
dopeyer
dopeyes
dopeying
dopeyly
dopeys
douchebag
douchebaged
douchebager
douchebages
douchebaging
douchebagly
douchebags
douchebagsed
douchebagser
douchebagses
douchebagsing
douchebagsly
douchebagss
doucheed
doucheer
douchees
doucheing
douchely
douches
douchey
doucheyed
doucheyer
doucheyes
doucheying
doucheyly
doucheys
drunk
drunked
drunker
drunkes
drunking
drunkly
drunks
dumass
dumassed
dumasser
dumasses
dumassing
dumassly
dumasss
dumbass
dumbassed
dumbasser
dumbasses
dumbassesed
dumbasseser
dumbasseses
dumbassesing
dumbassesly
dumbassess
dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
dummying
dummyly
dummys
dyke
dykeed
dykeer
dykees
dykeing
dykely
dykes
dykesed
dykeser
dykeses
dykesing
dykesly
dykess
erotic
eroticed
eroticer
erotices
eroticing
eroticly
erotics
extacy
extacyed
extacyer
extacyes
extacying
extacyly
extacys
extasy
extasyed
extasyer
extasyes
extasying
extasyly
extasys
fack
facked
facker
fackes
facking
fackly
facks
fag
faged
fager
fages
fagg
fagged
faggeded
faggeder
faggedes
faggeding
faggedly
faggeds
fagger
fagges
fagging
faggit
faggited
faggiter
faggites
faggiting
faggitly
faggits
faggly
faggot
faggoted
faggoter
faggotes
faggoting
faggotly
faggots
faggs
faging
fagly
fagot
fagoted
fagoter
fagotes
fagoting
fagotly
fagots
fags
fagsed
fagser
fagses
fagsing
fagsly
fagss
faig
faiged
faiger
faiges
faiging
faigly
faigs
faigt
faigted
faigter
faigtes
faigting
faigtly
faigts
fannybandit
fannybandited
fannybanditer
fannybandites
fannybanditing
fannybanditly
fannybandits
farted
farter
fartes
farting
fartknocker
fartknockered
fartknockerer
fartknockeres
fartknockering
fartknockerly
fartknockers
fartly
farts
felch
felched
felcher
felchered
felcherer
felcheres
felchering
felcherly
felchers
felches
felching
felchinged
felchinger
felchinges
felchinging
felchingly
felchings
felchly
felchs
fellate
fellateed
fellateer
fellatees
fellateing
fellately
fellates
fellatio
fellatioed
fellatioer
fellatioes
fellatioing
fellatioly
fellatios
feltch
feltched
feltcher
feltchered
feltcherer
feltcheres
feltchering
feltcherly
feltchers
feltches
feltching
feltchly
feltchs
feom
feomed
feomer
feomes
feoming
feomly
feoms
fisted
fisteded
fisteder
fistedes
fisteding
fistedly
fisteds
fisting
fistinged
fistinger
fistinges
fistinging
fistingly
fistings
fisty
fistyed
fistyer
fistyes
fistying
fistyly
fistys
floozy
floozyed
floozyer
floozyes
floozying
floozyly
floozys
foad
foaded
foader
foades
foading
foadly
foads
fondleed
fondleer
fondlees
fondleing
fondlely
fondles
foobar
foobared
foobarer
foobares
foobaring
foobarly
foobars
freex
freexed
freexer
freexes
freexing
freexly
freexs
frigg
frigga
friggaed
friggaer
friggaes
friggaing
friggaly
friggas
frigged
frigger
frigges
frigging
friggly
friggs
fubar
fubared
fubarer
fubares
fubaring
fubarly
fubars
fuck
fuckass
fuckassed
fuckasser
fuckasses
fuckassing
fuckassly
fuckasss
fucked
fuckeded
fuckeder
fuckedes
fuckeding
fuckedly
fuckeds
fucker
fuckered
fuckerer
fuckeres
fuckering
fuckerly
fuckers
fuckes
fuckface
fuckfaceed
fuckfaceer
fuckfacees
fuckfaceing
fuckfacely
fuckfaces
fuckin
fuckined
fuckiner
fuckines
fucking
fuckinged
fuckinger
fuckinges
fuckinging
fuckingly
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Is the levonorgestrel-releasing intrauterine system more effective than the copper IUD at preventing pregnancy?
Both the LNG-IUS and the copper IUD are highly effective at pregnancy prevention. However, large-scale comparative studies are lacking. These findings from the European Active Surveillance Study for Intrauterine Devices (EURAS IUD), an investigation of new users of the LNG-IUS (20 µg/day) and copper IUD (>30 different types) in Austria, Finland, Germany, Poland, Sweden, and the United Kingdom, confirm the low contraceptive failure rate for both devices.
The primary objective of this trial was to compare uterine perforation rates,1 but the results of a planned secondary analysis comparing contraceptive effectiveness may be of more interest to patients and providers.
Details of the study
Women who had a newly inserted IUD during the study period were eligible for recruitment. These women and their inserting health care provider then completed a follow-up questionnaire 12 months after enrollment to assess for pregnancy or any potential IUD complication.
In total, 61,448 women were enrolled, and 58,324 patients (41,001 using the LNG-IUS and 17,323 using the copper IUD) were included in the analysis. Only 1.7% of LNG-IUS users and 2.8% of copper IUD users were lost to follow-up. Women using the LNG-IUS were older than those using the copper IUD (mean age of 37.4 vs 33.3 years, respectively). About 43% and 24% of LNG-IUS and copper IUD users, respectively, were age 40 or older at the time of IUD insertion.
Strengths and limitations
The large sample size and low number of women lost to follow-up are strengths of this study. A major weakness: The indication for IUD insertion was not recorded. Nor was the risk of pregnancy assessed at enrollment.
Overall, the age of the study population was older than is typically found in a contraceptive efficacy trial, which generally covers the age range of 18 to 35 years.
Because women chose their type of IUD (as opposed to random allocation), variations in underlying fertility, age, and other confounders of efficacy cannot be accounted for fully with statistical analyses. The variation in age strongly suggests that women may have chosen the LNG-IUS for reasons other than contraception.
Furthermore, more than 30 types of copper IUDs were inserted during the study period, and small variations in contraceptive efficacy from one type to another may contribute to the overall difference in failure rates between the LNG-IUS and copper IUD. Although Heinemann and colleagues did perform an analysis of failure rates by copper content and found no differences between users of IUDs with less than 300 mm2 and those with at least 300 mm2 of copper, earlier prospective randomized trials show differences in contraceptive efficacy by device type and amount of copper.2
What this evidence means for practice
The LNG-IUS may be a more effective contraceptive than the copper IUD, but both possess excellent contraceptive efficacy. Prospective randomized trials, although much smaller than this nonrandomized cohort study, do not demonstrate differences in contraceptive efficacy between the LNG-IUS and copper IUD.3 The small difference in contraceptive failure rates (less than 1 in 200 women), if real, should not be the deciding factor for choosing one IUD over the other.
— Melissa J. Chen, MD, MPH, and Mitchell D. Creinin, MDShare your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Heinemann K, Reed S, Moehner S, Do Minh T. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015;91(4):274–279.
2. Thonneau PF, Almont T. Contraceptive efficacy of intrauterine devices. Am J Obstet Gynecol. 2008;198(3):248–253.
3. Sivin I, el Mahgoub S, McCarthy T, et al. Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T380Ag intrauterine devices: a five-year randomized study. Contraception. 1990;42(4):361–378.
Both the LNG-IUS and the copper IUD are highly effective at pregnancy prevention. However, large-scale comparative studies are lacking. These findings from the European Active Surveillance Study for Intrauterine Devices (EURAS IUD), an investigation of new users of the LNG-IUS (20 µg/day) and copper IUD (>30 different types) in Austria, Finland, Germany, Poland, Sweden, and the United Kingdom, confirm the low contraceptive failure rate for both devices.
The primary objective of this trial was to compare uterine perforation rates,1 but the results of a planned secondary analysis comparing contraceptive effectiveness may be of more interest to patients and providers.
Details of the study
Women who had a newly inserted IUD during the study period were eligible for recruitment. These women and their inserting health care provider then completed a follow-up questionnaire 12 months after enrollment to assess for pregnancy or any potential IUD complication.
In total, 61,448 women were enrolled, and 58,324 patients (41,001 using the LNG-IUS and 17,323 using the copper IUD) were included in the analysis. Only 1.7% of LNG-IUS users and 2.8% of copper IUD users were lost to follow-up. Women using the LNG-IUS were older than those using the copper IUD (mean age of 37.4 vs 33.3 years, respectively). About 43% and 24% of LNG-IUS and copper IUD users, respectively, were age 40 or older at the time of IUD insertion.
Strengths and limitations
The large sample size and low number of women lost to follow-up are strengths of this study. A major weakness: The indication for IUD insertion was not recorded. Nor was the risk of pregnancy assessed at enrollment.
Overall, the age of the study population was older than is typically found in a contraceptive efficacy trial, which generally covers the age range of 18 to 35 years.
Because women chose their type of IUD (as opposed to random allocation), variations in underlying fertility, age, and other confounders of efficacy cannot be accounted for fully with statistical analyses. The variation in age strongly suggests that women may have chosen the LNG-IUS for reasons other than contraception.
Furthermore, more than 30 types of copper IUDs were inserted during the study period, and small variations in contraceptive efficacy from one type to another may contribute to the overall difference in failure rates between the LNG-IUS and copper IUD. Although Heinemann and colleagues did perform an analysis of failure rates by copper content and found no differences between users of IUDs with less than 300 mm2 and those with at least 300 mm2 of copper, earlier prospective randomized trials show differences in contraceptive efficacy by device type and amount of copper.2
What this evidence means for practice
The LNG-IUS may be a more effective contraceptive than the copper IUD, but both possess excellent contraceptive efficacy. Prospective randomized trials, although much smaller than this nonrandomized cohort study, do not demonstrate differences in contraceptive efficacy between the LNG-IUS and copper IUD.3 The small difference in contraceptive failure rates (less than 1 in 200 women), if real, should not be the deciding factor for choosing one IUD over the other.
— Melissa J. Chen, MD, MPH, and Mitchell D. Creinin, MDShare your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Both the LNG-IUS and the copper IUD are highly effective at pregnancy prevention. However, large-scale comparative studies are lacking. These findings from the European Active Surveillance Study for Intrauterine Devices (EURAS IUD), an investigation of new users of the LNG-IUS (20 µg/day) and copper IUD (>30 different types) in Austria, Finland, Germany, Poland, Sweden, and the United Kingdom, confirm the low contraceptive failure rate for both devices.
The primary objective of this trial was to compare uterine perforation rates,1 but the results of a planned secondary analysis comparing contraceptive effectiveness may be of more interest to patients and providers.
Details of the study
Women who had a newly inserted IUD during the study period were eligible for recruitment. These women and their inserting health care provider then completed a follow-up questionnaire 12 months after enrollment to assess for pregnancy or any potential IUD complication.
In total, 61,448 women were enrolled, and 58,324 patients (41,001 using the LNG-IUS and 17,323 using the copper IUD) were included in the analysis. Only 1.7% of LNG-IUS users and 2.8% of copper IUD users were lost to follow-up. Women using the LNG-IUS were older than those using the copper IUD (mean age of 37.4 vs 33.3 years, respectively). About 43% and 24% of LNG-IUS and copper IUD users, respectively, were age 40 or older at the time of IUD insertion.
Strengths and limitations
The large sample size and low number of women lost to follow-up are strengths of this study. A major weakness: The indication for IUD insertion was not recorded. Nor was the risk of pregnancy assessed at enrollment.
Overall, the age of the study population was older than is typically found in a contraceptive efficacy trial, which generally covers the age range of 18 to 35 years.
Because women chose their type of IUD (as opposed to random allocation), variations in underlying fertility, age, and other confounders of efficacy cannot be accounted for fully with statistical analyses. The variation in age strongly suggests that women may have chosen the LNG-IUS for reasons other than contraception.
Furthermore, more than 30 types of copper IUDs were inserted during the study period, and small variations in contraceptive efficacy from one type to another may contribute to the overall difference in failure rates between the LNG-IUS and copper IUD. Although Heinemann and colleagues did perform an analysis of failure rates by copper content and found no differences between users of IUDs with less than 300 mm2 and those with at least 300 mm2 of copper, earlier prospective randomized trials show differences in contraceptive efficacy by device type and amount of copper.2
What this evidence means for practice
The LNG-IUS may be a more effective contraceptive than the copper IUD, but both possess excellent contraceptive efficacy. Prospective randomized trials, although much smaller than this nonrandomized cohort study, do not demonstrate differences in contraceptive efficacy between the LNG-IUS and copper IUD.3 The small difference in contraceptive failure rates (less than 1 in 200 women), if real, should not be the deciding factor for choosing one IUD over the other.
— Melissa J. Chen, MD, MPH, and Mitchell D. Creinin, MDShare your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Heinemann K, Reed S, Moehner S, Do Minh T. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015;91(4):274–279.
2. Thonneau PF, Almont T. Contraceptive efficacy of intrauterine devices. Am J Obstet Gynecol. 2008;198(3):248–253.
3. Sivin I, el Mahgoub S, McCarthy T, et al. Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T380Ag intrauterine devices: a five-year randomized study. Contraception. 1990;42(4):361–378.
1. Heinemann K, Reed S, Moehner S, Do Minh T. Risk of uterine perforation with levonorgestrel-releasing and copper intrauterine devices in the European Active Surveillance Study on Intrauterine Devices. Contraception. 2015;91(4):274–279.
2. Thonneau PF, Almont T. Contraceptive efficacy of intrauterine devices. Am J Obstet Gynecol. 2008;198(3):248–253.
3. Sivin I, el Mahgoub S, McCarthy T, et al. Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T380Ag intrauterine devices: a five-year randomized study. Contraception. 1990;42(4):361–378.
Why CMS’ plan to unbundle global surgery periods should be scrapped
Sometimes it’s difficult to figure out which way is forward. For the past few years, private insurers and the federal government (through the Medicare program) have been experimenting with and putting in place different ways of paying physicians for the care they provide. Many alternatives are designed to increase value for our nation’s health care dollars and improve quality of care, often through care coordination. Most involve different ways of “bundling” care—paying a single sum for a patient’s episode of care rather than separate payments each time a physician encounters a patient.
For more than 20 years, Medicare has bundled most surgeries, paying 1 sum to the physician and requiring only 1 copayment from the beneficiary patient. In this way, when a patient needs surgery, Medicare pays the surgeon 1 payment for preparation the day before surgery, for the surgery itself, and for either 10 or 90 days of follow-up care, depending on the specific procedure involved (TABLE 1). Similarly the patient has had 1 copay for the entire episode of care. This bundling is called global surgical codes, and it applies to coding, billing, and reimbursement.
Table 1: CMS description of 10- and 90-day global codes Minor procedures: 10-day postoperative period
Major procedures: 90-day postoperative period
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This approach may change soon—and not for the better. In this article, I describe how the federal Centers for Medicare and Medicaid Services (CMS) plan to eliminate global surgery bundling, as well as the efforts under way by the American Congress of Obstetricians and Gynecologists (ACOG) and other organizations to stop the proposed change.
The CMS plan to eliminate surgical bundling
In a significant twist from the trend toward bundling and care coordination, CMS finalized its proposed policy in its 2015 Medicare Physician Fee Schedule final rule to transition all 10- and 90-day global surgical codes to 0-day global surgical codes by 2017 and 2018, respectively. Beginning in 2017 for 10-day global codes and 2018 for 90-day codes, physicians will be paid separately for the day of surgery and for evaluation and management (E&M) provided on the day before and any days after. Patients will have copays for each physician intervention.
CMS has decided to move forward with this change despite overwhelming concern and opposition on the part of both patients and physicians. This change would affect more than 4,200 services on the Medicare Physician Fee Schedule—well over one-third of the 9,900 current procedural terminology (CPT) codes.
The new codes and increased paperwork and billing are daunting, and would result in an estimated 63 million additional claims per year to account for postsurgical E&M services. The cost to CMS alone for this huge new mountain of claims may be as high as $95 million per year. Moreover, under the new system, patients may not return for the full range of follow-up care needed if they get billed for every visit, possibly resulting in poorer outcomes.
CMS’ justification for unbundling
CMS argues that this change is needed because many surgeons are failing to provide as much care (as many E&M follow-up visits) as they’re paid to deliver under the 10- and 90-day codes. As evidence, CMS points to 3 reports published by the Department of Health and Human Services Office of Inspector General:
- An April 2009 report from the field of ocular surgery found that physicians provided fewer E&M services than were included in 201 of 300 examined global surgery fees. The cost of these undelivered services was approximately $97.6 million.1
- A May 2012 report from the field of cardiac surgery found that physicians provided fewer E&M services than were included in 132 global surgery fees of the 300 surgeries examined. The cost: $14.6 million.2
- Another May 2012 report, this one from the field of musculoskeletal surgery, found that physicians provided fewer E&M services than were included in 165 global surgery fees of the 300 surgeries examined. The cost for these undelivered services: $49 million.3
Based largely on these reports, CMS has determined that it cannot verify the number of visits, level of service, and relative costs of the services included in a global package, in large part because the current valuation methodology relies on survey data estimating the resources used in a typical case, instead of on actual data.
In each of these reports, the Inspector General also found smaller numbers of cases where surgeons provided more E&M care than was covered under the global payment. In each report, the Inspector General suggests that CMS should do more to identify and correctly value misvalued codes. ACOG Vice President for Health Policy Barbara Levy, MD, who is also chair of the Relative Value Scale Update Committee, or RUC, makes a compelling case that the RUC has identified and corrected many global surgical codes since these reports were issued and is in the process of revising more codes. She also argues that the RUC is the appropriate place to address these issues.
Policy analysis finds that total RVUs would decline
CMS has indicated that it intends to use a formula for converting the 10- and 90-day global services into 0-day services by simply reducing the work relative value units (RVUs) for the service by the number of work RVUs in the postoperative visits. The American College of Surgeons asked Health Policy Alternatives (HPA), a consulting firm, to analyze the CMS decision. HPA found that “systematically convert[ing] all global surgical codes to 0-day global codes by backing out of the bundled E&M services reduces the total RVUs and each component (work, practice expense, and malpractice) for surgical codes. Specifically, for surgical specialties, the impact of this transition on all Medicare reimbursed codes results in the following reductions:
- overall payment decrease of 1.8%
- payment decrease of 0.8% for work
- payment decrease of 2% for practice expense
- payment decrease of 9.2% for malpractice.
This modeling resulted in a total overall payment increase of 0.1% for generalists and a payment increase of 0.3% for medical specialists.”4
HPA’s findings related to the malpractice component are especially interesting for the ObGyn specialty. “Model results demonstrate that this policy results in significant redistribution of malpractice away from the main specialty provider of the surgical procedure into the entire group of providers (surgical and nonsurgical),” notes the HPA report.4 “Most impacted will be specialties with higher malpractice expenses, such as neurosurgeons and cardiac surgeons.”4 We could add ObGyns to that list.
ACOG cites numerous objections
ACOG is deeply involved in opposing this new CMS policy and preventing it from ever going into effect, working on our own, in coalition with our medical organization colleagues and patient organizations, and working closely with the US Congress.
ACOG and 28 other medical organizations, including the American Medical Association (AMA), summarized our opposition in a letter to US House and Senate Democratic and Republican leaders in December 2014, saying that this new policy:
Detracts from quality of care, impedes patient access, and complicates patient copays
- Patients will be responsible for copays on each service, including follow-up visits. This could considerably increase the administrative burden on patients. Worse, it could discourage them from returning for needed follow-up care.
- In the hospital critical care setting, the global payment structure allows the surgeon to oversee and coordinate care related to the patient’s recovery. Without the global structure, care will be fragmented and providers may compete to see patients and bill for the care they provide.
Undermines Medicare reform initiatives
- CMS initiatives for payment are all moving toward larger bundled payments. Deconstruction of the current payment structure for physicians is counterintuitive to the end goal of providing more comprehensive and coordinated care for the patient.
- Current bipartisan, bicameral legislation to repeal and replace the flawed sustainable growth rate formula calls for “a period of stability” in physician pay to allow physicians to transition to alternative payment models. The proposal to unbundle global surgical periods will add new complexities to an already flawed system and stymie progress.
Increases administrative burden
- The administrative burden on surgical practices and CMS (and its contractors) will be significant. Eliminating the global package will result in 63 million additional claims per year, adding unnecessary costs to our health care system.
Obstructs clinical registry data collection and quality improvement
- Surgeons will have less ability to collect information on patient outcomes in clinical registries, undermining many of the most meaningful quality improvement initiatives.5
Additional ACOG concerns
ACOG added these concerns to our opposition to the CMS plan:
- The change will not accurately account for physician work, practice expense, and malpractice risk for services performed.
- Thousands of new codes and/or values will need to be created for postoperative care because the supplies and equipment needed for postoperative care are not included in the E&M codes that will be used to report in-hospital and outpatient postoperative services (TABLE 2).
- Liability costs of a specific service should be derived from those of the performing specialties. Under the CMS plan, the liability costs associated with postoperative work would be removed from the primary service and artificially diluted by the wide mix of specialties performing all types of E&M services. Without global periods, a one-size-fits-all approach to professional liability insurance will be unsustainable and result in great disparities between the actual and realized malpractice costs for many physician specialties.
Table 2: Other postoperative care services currently bundled into global surgical packages
|
We have important allies
The American Association of Retired Persons (AARP) joined us in September 2014, when it formally asked CMS to abandon this new policy. In a letter to CMS Administrator Marilyn Tavenner, AARP noted that, “from a beneficiary perspective, we are concerned that this unbundling could produce considerable confusion and cause beneficiaries to receive multiple explanations of Medicare benefits (and incur separate cost-sharing obligations) related to a single surgical procedure….[G]iven the obvious methodological uncertainty and complexity involved in determining appropriate values for a very large number of ‘new’ 0-day global services, and the likely confusion surrounding the resulting increase in Medicare claims, AARP has serious doubts regarding the benefit of this unbundling proposal. We suggest [that] CMS consider other available alternatives, including the re-valuation of global services whose current values are believed to be incorrect.”6
Also in September, 27 Republican and Democratic members of Congress wrote a strong letter to CMS echoing the medical community’s concerns. The letter and many months of congressional leadership have been spearheaded by Representatives Larry Bucshon, MD, and Ami Bera, MD—demonstrating the value of having physicians in elective office. Other physician members of Congress who have provided outstanding leadership include ACOG Fellows and Representatives Michael Burgess, MD, and Phil Roe, MD, as well as Representatives Tom Price, MD; Andy Harris, MD; Joe Heck, DO; Charles Boustany, MD; Raul Ruiz, MD; and Dan Benishek, MD.
This important group of physician leaders, ACOG, AARP, and the surgical community are hard at work to derail or significantly delay what most physicians and policy analysts see as a very bad idea.
Congress takes action
In April 2015, Congress passed HR2, the Medicare Access and CHIP Reauthorization Bill, which most notably repealed the Medicare Sustainable Growth Rate formula. Included in this law is an important provision to halt implementation of CMS’ plan to unbundle all 10- and 90-day global codes.
Section 523 of that law requires CMS to periodically collect information on the services that surgeons furnish during these global periods, beginning no later than 2017, and use that information to ensure that the bundled payment amounts for surgical services are accurate. The Secretary of Health and Human Services is given the authority to withhold a portion of payment for services with a 10- or 90-day global period to incentivize the reporting of information. The Secretary can stop collecting this information from surgeons once the needed data can be obtained through other mechanisms, such as clinical data registries and electronic medical records.
Congressmen Bucshon and Bera championed this provision, along with nearly all physician members of the US House of Representatives. This change ensures a thorough, data-driven approach to appropriately valuing surgical services, including those provided by ObGyn subspecialists, such as urogynecologists and gynecologic oncologists.
Acknowledgment
The author thanks Barbara Levy, MD, ACOG Vice President for Health Policy, for her helpful comments.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Department of Health and Human Services, Office of Inspector General. Nationwide Review of Evaluation and Management Services Included in Eye and Ocular Adnexa Global Surgery Fees for Calendar Year 2005. A-05-07-00077. Washington, DC: Department of Health and Human Services; April 2009.
2. Department of Health and Human Services, Office of Inspector General. Cardiovascular Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00054. Washington, DC: Department of Health and Human Services; May 2012.
3. Department of Health and Human Services, Office of Inspector General. Musculoskeletal Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00053. Washington, DC: Department of Health and Human Services; May 2012.
4. Summary of Initial Modeling Results of the CMS Policy to Transition 10- and 90-Day Global Surgery Codes to 0-Day Global Surgery Codes. Washington, DC: Health Policy Alternatives; January 9, 2015.
5. American Congress of Obstetricians and Gynecologists joint letter to Congress; December 2, 2014.
6. American Association of Retired Persons letter to Marilyn Tavenner, Administrator, Centers for Medicare and Medicaid Services; September 2, 2014.
Sometimes it’s difficult to figure out which way is forward. For the past few years, private insurers and the federal government (through the Medicare program) have been experimenting with and putting in place different ways of paying physicians for the care they provide. Many alternatives are designed to increase value for our nation’s health care dollars and improve quality of care, often through care coordination. Most involve different ways of “bundling” care—paying a single sum for a patient’s episode of care rather than separate payments each time a physician encounters a patient.
For more than 20 years, Medicare has bundled most surgeries, paying 1 sum to the physician and requiring only 1 copayment from the beneficiary patient. In this way, when a patient needs surgery, Medicare pays the surgeon 1 payment for preparation the day before surgery, for the surgery itself, and for either 10 or 90 days of follow-up care, depending on the specific procedure involved (TABLE 1). Similarly the patient has had 1 copay for the entire episode of care. This bundling is called global surgical codes, and it applies to coding, billing, and reimbursement.
Table 1: CMS description of 10- and 90-day global codes Minor procedures: 10-day postoperative period
Major procedures: 90-day postoperative period
|
This approach may change soon—and not for the better. In this article, I describe how the federal Centers for Medicare and Medicaid Services (CMS) plan to eliminate global surgery bundling, as well as the efforts under way by the American Congress of Obstetricians and Gynecologists (ACOG) and other organizations to stop the proposed change.
The CMS plan to eliminate surgical bundling
In a significant twist from the trend toward bundling and care coordination, CMS finalized its proposed policy in its 2015 Medicare Physician Fee Schedule final rule to transition all 10- and 90-day global surgical codes to 0-day global surgical codes by 2017 and 2018, respectively. Beginning in 2017 for 10-day global codes and 2018 for 90-day codes, physicians will be paid separately for the day of surgery and for evaluation and management (E&M) provided on the day before and any days after. Patients will have copays for each physician intervention.
CMS has decided to move forward with this change despite overwhelming concern and opposition on the part of both patients and physicians. This change would affect more than 4,200 services on the Medicare Physician Fee Schedule—well over one-third of the 9,900 current procedural terminology (CPT) codes.
The new codes and increased paperwork and billing are daunting, and would result in an estimated 63 million additional claims per year to account for postsurgical E&M services. The cost to CMS alone for this huge new mountain of claims may be as high as $95 million per year. Moreover, under the new system, patients may not return for the full range of follow-up care needed if they get billed for every visit, possibly resulting in poorer outcomes.
CMS’ justification for unbundling
CMS argues that this change is needed because many surgeons are failing to provide as much care (as many E&M follow-up visits) as they’re paid to deliver under the 10- and 90-day codes. As evidence, CMS points to 3 reports published by the Department of Health and Human Services Office of Inspector General:
- An April 2009 report from the field of ocular surgery found that physicians provided fewer E&M services than were included in 201 of 300 examined global surgery fees. The cost of these undelivered services was approximately $97.6 million.1
- A May 2012 report from the field of cardiac surgery found that physicians provided fewer E&M services than were included in 132 global surgery fees of the 300 surgeries examined. The cost: $14.6 million.2
- Another May 2012 report, this one from the field of musculoskeletal surgery, found that physicians provided fewer E&M services than were included in 165 global surgery fees of the 300 surgeries examined. The cost for these undelivered services: $49 million.3
Based largely on these reports, CMS has determined that it cannot verify the number of visits, level of service, and relative costs of the services included in a global package, in large part because the current valuation methodology relies on survey data estimating the resources used in a typical case, instead of on actual data.
In each of these reports, the Inspector General also found smaller numbers of cases where surgeons provided more E&M care than was covered under the global payment. In each report, the Inspector General suggests that CMS should do more to identify and correctly value misvalued codes. ACOG Vice President for Health Policy Barbara Levy, MD, who is also chair of the Relative Value Scale Update Committee, or RUC, makes a compelling case that the RUC has identified and corrected many global surgical codes since these reports were issued and is in the process of revising more codes. She also argues that the RUC is the appropriate place to address these issues.
Policy analysis finds that total RVUs would decline
CMS has indicated that it intends to use a formula for converting the 10- and 90-day global services into 0-day services by simply reducing the work relative value units (RVUs) for the service by the number of work RVUs in the postoperative visits. The American College of Surgeons asked Health Policy Alternatives (HPA), a consulting firm, to analyze the CMS decision. HPA found that “systematically convert[ing] all global surgical codes to 0-day global codes by backing out of the bundled E&M services reduces the total RVUs and each component (work, practice expense, and malpractice) for surgical codes. Specifically, for surgical specialties, the impact of this transition on all Medicare reimbursed codes results in the following reductions:
- overall payment decrease of 1.8%
- payment decrease of 0.8% for work
- payment decrease of 2% for practice expense
- payment decrease of 9.2% for malpractice.
This modeling resulted in a total overall payment increase of 0.1% for generalists and a payment increase of 0.3% for medical specialists.”4
HPA’s findings related to the malpractice component are especially interesting for the ObGyn specialty. “Model results demonstrate that this policy results in significant redistribution of malpractice away from the main specialty provider of the surgical procedure into the entire group of providers (surgical and nonsurgical),” notes the HPA report.4 “Most impacted will be specialties with higher malpractice expenses, such as neurosurgeons and cardiac surgeons.”4 We could add ObGyns to that list.
ACOG cites numerous objections
ACOG is deeply involved in opposing this new CMS policy and preventing it from ever going into effect, working on our own, in coalition with our medical organization colleagues and patient organizations, and working closely with the US Congress.
ACOG and 28 other medical organizations, including the American Medical Association (AMA), summarized our opposition in a letter to US House and Senate Democratic and Republican leaders in December 2014, saying that this new policy:
Detracts from quality of care, impedes patient access, and complicates patient copays
- Patients will be responsible for copays on each service, including follow-up visits. This could considerably increase the administrative burden on patients. Worse, it could discourage them from returning for needed follow-up care.
- In the hospital critical care setting, the global payment structure allows the surgeon to oversee and coordinate care related to the patient’s recovery. Without the global structure, care will be fragmented and providers may compete to see patients and bill for the care they provide.
Undermines Medicare reform initiatives
- CMS initiatives for payment are all moving toward larger bundled payments. Deconstruction of the current payment structure for physicians is counterintuitive to the end goal of providing more comprehensive and coordinated care for the patient.
- Current bipartisan, bicameral legislation to repeal and replace the flawed sustainable growth rate formula calls for “a period of stability” in physician pay to allow physicians to transition to alternative payment models. The proposal to unbundle global surgical periods will add new complexities to an already flawed system and stymie progress.
Increases administrative burden
- The administrative burden on surgical practices and CMS (and its contractors) will be significant. Eliminating the global package will result in 63 million additional claims per year, adding unnecessary costs to our health care system.
Obstructs clinical registry data collection and quality improvement
- Surgeons will have less ability to collect information on patient outcomes in clinical registries, undermining many of the most meaningful quality improvement initiatives.5
Additional ACOG concerns
ACOG added these concerns to our opposition to the CMS plan:
- The change will not accurately account for physician work, practice expense, and malpractice risk for services performed.
- Thousands of new codes and/or values will need to be created for postoperative care because the supplies and equipment needed for postoperative care are not included in the E&M codes that will be used to report in-hospital and outpatient postoperative services (TABLE 2).
- Liability costs of a specific service should be derived from those of the performing specialties. Under the CMS plan, the liability costs associated with postoperative work would be removed from the primary service and artificially diluted by the wide mix of specialties performing all types of E&M services. Without global periods, a one-size-fits-all approach to professional liability insurance will be unsustainable and result in great disparities between the actual and realized malpractice costs for many physician specialties.
Table 2: Other postoperative care services currently bundled into global surgical packages
|
We have important allies
The American Association of Retired Persons (AARP) joined us in September 2014, when it formally asked CMS to abandon this new policy. In a letter to CMS Administrator Marilyn Tavenner, AARP noted that, “from a beneficiary perspective, we are concerned that this unbundling could produce considerable confusion and cause beneficiaries to receive multiple explanations of Medicare benefits (and incur separate cost-sharing obligations) related to a single surgical procedure….[G]iven the obvious methodological uncertainty and complexity involved in determining appropriate values for a very large number of ‘new’ 0-day global services, and the likely confusion surrounding the resulting increase in Medicare claims, AARP has serious doubts regarding the benefit of this unbundling proposal. We suggest [that] CMS consider other available alternatives, including the re-valuation of global services whose current values are believed to be incorrect.”6
Also in September, 27 Republican and Democratic members of Congress wrote a strong letter to CMS echoing the medical community’s concerns. The letter and many months of congressional leadership have been spearheaded by Representatives Larry Bucshon, MD, and Ami Bera, MD—demonstrating the value of having physicians in elective office. Other physician members of Congress who have provided outstanding leadership include ACOG Fellows and Representatives Michael Burgess, MD, and Phil Roe, MD, as well as Representatives Tom Price, MD; Andy Harris, MD; Joe Heck, DO; Charles Boustany, MD; Raul Ruiz, MD; and Dan Benishek, MD.
This important group of physician leaders, ACOG, AARP, and the surgical community are hard at work to derail or significantly delay what most physicians and policy analysts see as a very bad idea.
Congress takes action
In April 2015, Congress passed HR2, the Medicare Access and CHIP Reauthorization Bill, which most notably repealed the Medicare Sustainable Growth Rate formula. Included in this law is an important provision to halt implementation of CMS’ plan to unbundle all 10- and 90-day global codes.
Section 523 of that law requires CMS to periodically collect information on the services that surgeons furnish during these global periods, beginning no later than 2017, and use that information to ensure that the bundled payment amounts for surgical services are accurate. The Secretary of Health and Human Services is given the authority to withhold a portion of payment for services with a 10- or 90-day global period to incentivize the reporting of information. The Secretary can stop collecting this information from surgeons once the needed data can be obtained through other mechanisms, such as clinical data registries and electronic medical records.
Congressmen Bucshon and Bera championed this provision, along with nearly all physician members of the US House of Representatives. This change ensures a thorough, data-driven approach to appropriately valuing surgical services, including those provided by ObGyn subspecialists, such as urogynecologists and gynecologic oncologists.
Acknowledgment
The author thanks Barbara Levy, MD, ACOG Vice President for Health Policy, for her helpful comments.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Sometimes it’s difficult to figure out which way is forward. For the past few years, private insurers and the federal government (through the Medicare program) have been experimenting with and putting in place different ways of paying physicians for the care they provide. Many alternatives are designed to increase value for our nation’s health care dollars and improve quality of care, often through care coordination. Most involve different ways of “bundling” care—paying a single sum for a patient’s episode of care rather than separate payments each time a physician encounters a patient.
For more than 20 years, Medicare has bundled most surgeries, paying 1 sum to the physician and requiring only 1 copayment from the beneficiary patient. In this way, when a patient needs surgery, Medicare pays the surgeon 1 payment for preparation the day before surgery, for the surgery itself, and for either 10 or 90 days of follow-up care, depending on the specific procedure involved (TABLE 1). Similarly the patient has had 1 copay for the entire episode of care. This bundling is called global surgical codes, and it applies to coding, billing, and reimbursement.
Table 1: CMS description of 10- and 90-day global codes Minor procedures: 10-day postoperative period
Major procedures: 90-day postoperative period
|
This approach may change soon—and not for the better. In this article, I describe how the federal Centers for Medicare and Medicaid Services (CMS) plan to eliminate global surgery bundling, as well as the efforts under way by the American Congress of Obstetricians and Gynecologists (ACOG) and other organizations to stop the proposed change.
The CMS plan to eliminate surgical bundling
In a significant twist from the trend toward bundling and care coordination, CMS finalized its proposed policy in its 2015 Medicare Physician Fee Schedule final rule to transition all 10- and 90-day global surgical codes to 0-day global surgical codes by 2017 and 2018, respectively. Beginning in 2017 for 10-day global codes and 2018 for 90-day codes, physicians will be paid separately for the day of surgery and for evaluation and management (E&M) provided on the day before and any days after. Patients will have copays for each physician intervention.
CMS has decided to move forward with this change despite overwhelming concern and opposition on the part of both patients and physicians. This change would affect more than 4,200 services on the Medicare Physician Fee Schedule—well over one-third of the 9,900 current procedural terminology (CPT) codes.
The new codes and increased paperwork and billing are daunting, and would result in an estimated 63 million additional claims per year to account for postsurgical E&M services. The cost to CMS alone for this huge new mountain of claims may be as high as $95 million per year. Moreover, under the new system, patients may not return for the full range of follow-up care needed if they get billed for every visit, possibly resulting in poorer outcomes.
CMS’ justification for unbundling
CMS argues that this change is needed because many surgeons are failing to provide as much care (as many E&M follow-up visits) as they’re paid to deliver under the 10- and 90-day codes. As evidence, CMS points to 3 reports published by the Department of Health and Human Services Office of Inspector General:
- An April 2009 report from the field of ocular surgery found that physicians provided fewer E&M services than were included in 201 of 300 examined global surgery fees. The cost of these undelivered services was approximately $97.6 million.1
- A May 2012 report from the field of cardiac surgery found that physicians provided fewer E&M services than were included in 132 global surgery fees of the 300 surgeries examined. The cost: $14.6 million.2
- Another May 2012 report, this one from the field of musculoskeletal surgery, found that physicians provided fewer E&M services than were included in 165 global surgery fees of the 300 surgeries examined. The cost for these undelivered services: $49 million.3
Based largely on these reports, CMS has determined that it cannot verify the number of visits, level of service, and relative costs of the services included in a global package, in large part because the current valuation methodology relies on survey data estimating the resources used in a typical case, instead of on actual data.
In each of these reports, the Inspector General also found smaller numbers of cases where surgeons provided more E&M care than was covered under the global payment. In each report, the Inspector General suggests that CMS should do more to identify and correctly value misvalued codes. ACOG Vice President for Health Policy Barbara Levy, MD, who is also chair of the Relative Value Scale Update Committee, or RUC, makes a compelling case that the RUC has identified and corrected many global surgical codes since these reports were issued and is in the process of revising more codes. She also argues that the RUC is the appropriate place to address these issues.
Policy analysis finds that total RVUs would decline
CMS has indicated that it intends to use a formula for converting the 10- and 90-day global services into 0-day services by simply reducing the work relative value units (RVUs) for the service by the number of work RVUs in the postoperative visits. The American College of Surgeons asked Health Policy Alternatives (HPA), a consulting firm, to analyze the CMS decision. HPA found that “systematically convert[ing] all global surgical codes to 0-day global codes by backing out of the bundled E&M services reduces the total RVUs and each component (work, practice expense, and malpractice) for surgical codes. Specifically, for surgical specialties, the impact of this transition on all Medicare reimbursed codes results in the following reductions:
- overall payment decrease of 1.8%
- payment decrease of 0.8% for work
- payment decrease of 2% for practice expense
- payment decrease of 9.2% for malpractice.
This modeling resulted in a total overall payment increase of 0.1% for generalists and a payment increase of 0.3% for medical specialists.”4
HPA’s findings related to the malpractice component are especially interesting for the ObGyn specialty. “Model results demonstrate that this policy results in significant redistribution of malpractice away from the main specialty provider of the surgical procedure into the entire group of providers (surgical and nonsurgical),” notes the HPA report.4 “Most impacted will be specialties with higher malpractice expenses, such as neurosurgeons and cardiac surgeons.”4 We could add ObGyns to that list.
ACOG cites numerous objections
ACOG is deeply involved in opposing this new CMS policy and preventing it from ever going into effect, working on our own, in coalition with our medical organization colleagues and patient organizations, and working closely with the US Congress.
ACOG and 28 other medical organizations, including the American Medical Association (AMA), summarized our opposition in a letter to US House and Senate Democratic and Republican leaders in December 2014, saying that this new policy:
Detracts from quality of care, impedes patient access, and complicates patient copays
- Patients will be responsible for copays on each service, including follow-up visits. This could considerably increase the administrative burden on patients. Worse, it could discourage them from returning for needed follow-up care.
- In the hospital critical care setting, the global payment structure allows the surgeon to oversee and coordinate care related to the patient’s recovery. Without the global structure, care will be fragmented and providers may compete to see patients and bill for the care they provide.
Undermines Medicare reform initiatives
- CMS initiatives for payment are all moving toward larger bundled payments. Deconstruction of the current payment structure for physicians is counterintuitive to the end goal of providing more comprehensive and coordinated care for the patient.
- Current bipartisan, bicameral legislation to repeal and replace the flawed sustainable growth rate formula calls for “a period of stability” in physician pay to allow physicians to transition to alternative payment models. The proposal to unbundle global surgical periods will add new complexities to an already flawed system and stymie progress.
Increases administrative burden
- The administrative burden on surgical practices and CMS (and its contractors) will be significant. Eliminating the global package will result in 63 million additional claims per year, adding unnecessary costs to our health care system.
Obstructs clinical registry data collection and quality improvement
- Surgeons will have less ability to collect information on patient outcomes in clinical registries, undermining many of the most meaningful quality improvement initiatives.5
Additional ACOG concerns
ACOG added these concerns to our opposition to the CMS plan:
- The change will not accurately account for physician work, practice expense, and malpractice risk for services performed.
- Thousands of new codes and/or values will need to be created for postoperative care because the supplies and equipment needed for postoperative care are not included in the E&M codes that will be used to report in-hospital and outpatient postoperative services (TABLE 2).
- Liability costs of a specific service should be derived from those of the performing specialties. Under the CMS plan, the liability costs associated with postoperative work would be removed from the primary service and artificially diluted by the wide mix of specialties performing all types of E&M services. Without global periods, a one-size-fits-all approach to professional liability insurance will be unsustainable and result in great disparities between the actual and realized malpractice costs for many physician specialties.
Table 2: Other postoperative care services currently bundled into global surgical packages
|
We have important allies
The American Association of Retired Persons (AARP) joined us in September 2014, when it formally asked CMS to abandon this new policy. In a letter to CMS Administrator Marilyn Tavenner, AARP noted that, “from a beneficiary perspective, we are concerned that this unbundling could produce considerable confusion and cause beneficiaries to receive multiple explanations of Medicare benefits (and incur separate cost-sharing obligations) related to a single surgical procedure….[G]iven the obvious methodological uncertainty and complexity involved in determining appropriate values for a very large number of ‘new’ 0-day global services, and the likely confusion surrounding the resulting increase in Medicare claims, AARP has serious doubts regarding the benefit of this unbundling proposal. We suggest [that] CMS consider other available alternatives, including the re-valuation of global services whose current values are believed to be incorrect.”6
Also in September, 27 Republican and Democratic members of Congress wrote a strong letter to CMS echoing the medical community’s concerns. The letter and many months of congressional leadership have been spearheaded by Representatives Larry Bucshon, MD, and Ami Bera, MD—demonstrating the value of having physicians in elective office. Other physician members of Congress who have provided outstanding leadership include ACOG Fellows and Representatives Michael Burgess, MD, and Phil Roe, MD, as well as Representatives Tom Price, MD; Andy Harris, MD; Joe Heck, DO; Charles Boustany, MD; Raul Ruiz, MD; and Dan Benishek, MD.
This important group of physician leaders, ACOG, AARP, and the surgical community are hard at work to derail or significantly delay what most physicians and policy analysts see as a very bad idea.
Congress takes action
In April 2015, Congress passed HR2, the Medicare Access and CHIP Reauthorization Bill, which most notably repealed the Medicare Sustainable Growth Rate formula. Included in this law is an important provision to halt implementation of CMS’ plan to unbundle all 10- and 90-day global codes.
Section 523 of that law requires CMS to periodically collect information on the services that surgeons furnish during these global periods, beginning no later than 2017, and use that information to ensure that the bundled payment amounts for surgical services are accurate. The Secretary of Health and Human Services is given the authority to withhold a portion of payment for services with a 10- or 90-day global period to incentivize the reporting of information. The Secretary can stop collecting this information from surgeons once the needed data can be obtained through other mechanisms, such as clinical data registries and electronic medical records.
Congressmen Bucshon and Bera championed this provision, along with nearly all physician members of the US House of Representatives. This change ensures a thorough, data-driven approach to appropriately valuing surgical services, including those provided by ObGyn subspecialists, such as urogynecologists and gynecologic oncologists.
Acknowledgment
The author thanks Barbara Levy, MD, ACOG Vice President for Health Policy, for her helpful comments.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Department of Health and Human Services, Office of Inspector General. Nationwide Review of Evaluation and Management Services Included in Eye and Ocular Adnexa Global Surgery Fees for Calendar Year 2005. A-05-07-00077. Washington, DC: Department of Health and Human Services; April 2009.
2. Department of Health and Human Services, Office of Inspector General. Cardiovascular Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00054. Washington, DC: Department of Health and Human Services; May 2012.
3. Department of Health and Human Services, Office of Inspector General. Musculoskeletal Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00053. Washington, DC: Department of Health and Human Services; May 2012.
4. Summary of Initial Modeling Results of the CMS Policy to Transition 10- and 90-Day Global Surgery Codes to 0-Day Global Surgery Codes. Washington, DC: Health Policy Alternatives; January 9, 2015.
5. American Congress of Obstetricians and Gynecologists joint letter to Congress; December 2, 2014.
6. American Association of Retired Persons letter to Marilyn Tavenner, Administrator, Centers for Medicare and Medicaid Services; September 2, 2014.
1. Department of Health and Human Services, Office of Inspector General. Nationwide Review of Evaluation and Management Services Included in Eye and Ocular Adnexa Global Surgery Fees for Calendar Year 2005. A-05-07-00077. Washington, DC: Department of Health and Human Services; April 2009.
2. Department of Health and Human Services, Office of Inspector General. Cardiovascular Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00054. Washington, DC: Department of Health and Human Services; May 2012.
3. Department of Health and Human Services, Office of Inspector General. Musculoskeletal Global Surgery Fees Often Did Not Reflect the Number of Evaluation and Management Services Provided. A-05-09-00053. Washington, DC: Department of Health and Human Services; May 2012.
4. Summary of Initial Modeling Results of the CMS Policy to Transition 10- and 90-Day Global Surgery Codes to 0-Day Global Surgery Codes. Washington, DC: Health Policy Alternatives; January 9, 2015.
5. American Congress of Obstetricians and Gynecologists joint letter to Congress; December 2, 2014.
6. American Association of Retired Persons letter to Marilyn Tavenner, Administrator, Centers for Medicare and Medicaid Services; September 2, 2014.
Delayed birth, intubation failure: $10M settlement
Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring.
The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities.
Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.
Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.
Verdict A $10 million Washington settlement was reached.
Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale.
Patient’s claim The risks and benefits of the OC were not fully explained to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.
Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.
Verdict A Washington defense verdict was returned.
Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed.
Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.
Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.
Verdict A $484,141 Mississippi verdict was returned.
Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her.
Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.
Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.
Verdict A $270,000 Washington verdict was returned.
Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.
The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.
The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel.
Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.
Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with postanesthesia residuals.
Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.
Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.
The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.
The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.
The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care.
Parents’ claim The mother and fetus were never properly assessed or treated.
Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.
Verdict A Texas defense verdict was returned.
Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care.
Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.
Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.
Verdict An $8.4 million Georgia verdict was returned.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring.
The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities.
Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.
Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.
Verdict A $10 million Washington settlement was reached.
Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale.
Patient’s claim The risks and benefits of the OC were not fully explained to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.
Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.
Verdict A Washington defense verdict was returned.
Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed.
Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.
Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.
Verdict A $484,141 Mississippi verdict was returned.
Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her.
Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.
Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.
Verdict A $270,000 Washington verdict was returned.
Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.
The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.
The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel.
Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.
Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with postanesthesia residuals.
Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.
Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.
The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.
The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.
The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care.
Parents’ claim The mother and fetus were never properly assessed or treated.
Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.
Verdict A Texas defense verdict was returned.
Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care.
Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.
Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.
Verdict An $8.4 million Georgia verdict was returned.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Delayed birth, intubation failure: $10M settlement
Two days shy of her due date, a woman went to an Army hospital to report bloody mucus discharge and sporadic contractions. She was 2 cm dilated and 50% effaced with the baby at –2 station. Fetal heart-rate monitor results were reassuring. She was discharged home but returned 5 hours later with increased pain and contractions. She was 5 cm dilated, 90% effaced; the baby was at –3 station. When contractions ceased, she was discharged. There had been no cervical change for 6 hours with a negative fern test. Fetal monitoring results were reassuring.
The woman returned 3 hours later with increased pain and contractions. She had a fever and high white blood cell and neutrophil counts. She was 6 cm dilated, 90% effaced, but the baby was still at –3 station. Ampicillin sodium/sulbactam sodium was administered. The ObGyn was called 4 times over the next 2.5 hours, when fetal monitoring results worsened and bradycardia developed. The nurses treated fetal distress by changing the maternal position and performing amnioinfusion. Then the ObGyn came to the bedside and ordered cesarean delivery. The baby was born severely compromised from hypoxic ischemic encephalopathy and metabolic acidosis. The pediatrician responsible for the baby’s resuscitation failed to get a response with bag ventilation after 5 minutes; 2 attempts at intubation failed. When the chief of pediatrics arrived at 15 minutes, the infant was successfully intubated. The baby was transferred to another facility. The child has profound disabilities.
Parents’ claim The hospital staff and physician did not deliver the baby in a timely manner when fetal distress was first noted. The pediatrician did not properly resuscitate the newborn.
Defendants’ defense Chorioamnionitis and funisitis caused or contributed to the infant’s injuries. Proper care was provided.
Verdict A $10 million Washington settlement was reached.
Did OCs cause this woman’s stroke?
A 40-year-old woman went to a clinic to obtain a prescription for birth control pills. A physician assistant (PA) conducted a complete physical examination. When no contraindications were found, a prescription for oral contraceptives (OCs) was provided. Two months later, the patient suffered a debilitating stroke. After the stroke, the patient was found to have a patent foramen ovale.
Patient’s claim The risks and benefits of the OC were not fully explained to the patient by the PA. She was not offered other contraceptive options. OCs are not safe for a woman her age due to a higher risk of stroke.
Defendants’ defense The patient used OCs in the past, and had received information from other physicians about their use. The stroke occurred because of the foramen ovale, not the use of OCs.
Verdict A Washington defense verdict was returned.
Ureter injury not treated until the next day
During cesarean delivery, the ObGyn identified a small ureteral injury but did not repair it. The next day, the ObGyn consulted a urologist and ordered an intravenous pyelogram (IVP). The urologist identified a ureteral obstruction and surgically repaired the injury. The patient was required to use a nephros-tomy bag for 6 months until the nephrostomy was reversed.
Patient’s claim The ObGyn was negligent in failing to immediately treat the ureter injury. The delay in repair necessitated the use of the nephrostomy bag.
Physician’s defense A ureter injury is a known complication of the procedure. The ObGyn did not cause the obstruction. Failure to perform an immediate repair was due to his concern that the patient might have lost too much blood during cesarean delivery. Bringing in the urologist the next day was appropriate. The patient completely recovered.
Verdict A $484,141 Mississippi verdict was returned.
Patient didn’t want male physician
After a woman experienced sexual assault in college, she did not want a male physician to perform a vaginal examination. When pregnant, she discussed that request with her nurse midwives. While she was in labor, a male ObGyn examined her.
Patient’s claim The nurse midwives failed to document her request not to be examined by a male clinician. The patient experienced severe emotional distress.
Defendants’ defense The midwives claimed they were never told of the patient’s aversion to having a male physician examine her. The male physician and the birthing center denied knowledge of the request.
Verdict A $270,000 Washington verdict was returned.
Symptoms attributed to anesthesia: $2M
A 62-year-old woman underwent treatment for abnormal uterine bleeding (AUB). Hysteroscopy revealed a retroverted uterus containing a 3-cm polyp. During resection of the polyp, the uterus was perforated and bowel was drawn into the uterus. The injury was not recognized. The patient was discharged home the same day.
The next day, she phoned to report vomiting, abdominal pain, and urinary retention. The gynecologist attributed the symptoms to anesthesia and told the patient to allow more time for resolution.
The patient went to an emergency department (ED) 48 hours later with a distended abdomen and severe pain. She was transferred to a regional hospital with acute sepsis. A small bowel perforation was identified, requiring extensive treatment, including hysterectomy and resection of 27 cm of small bowel.
Patient’s claim The gynecologist was negligent in failing to recognize the injury intraoperatively. He didn’t examine the patient when she first reported symptoms.
Physician’s defense The injuries are known risks of the procedure. The patient’s complaints could reasonably be associated with postanesthesia residuals.
Verdict A $5 million Virginia verdict was reduced to $2 million by the statutory cap.
Did nosebleeds cause baby’s disabilities?
After a 33-year-old woman had a nosebleed she noted decreased fetal movement. At the ED, preterm labor was ruled out, fetal monitoring results were normal, and she was discharged. She returned that afternoon with a nosebleed. After 4 hours, when fetal monitoring results were normal, she was again discharged.
The next morning, an otolaryngologist cauterized her right nostril. After another nosebleed, the physician packed the right nasal cavity. She returned with bleeding from the left nostril and remained at the ear, nose, and throat (ENT) clinic for several hours until the bleeding stopped.
The following day, she returned to the ENT clinic asking that the packing be removed, but it needed to remain. She called a covering ObGyn to request anti-anxiety medication because the packing was making her feel claustrophobic.
The next day, after additional nosebleeds, she was taken to the ED with mild contractions. Her hematocrit was 25.6% and her hemoglobin level was 8.8 g/dL. When fetal heart-rate monitoring was nonreassuring, a cesarean delivery was expedited. The child has profound physical and developmental disabilities, uses a feeding tube and ventilator, and needs 24-hour care.
Parents’ claim The mother and fetus were never properly assessed or treated.
Defendants’ defense The physicians denied negligence and disputed the severity of most of the nosebleeds. At each ED presentation, hematocrit and hemoglobin levels were normal and the mother was stable at discharge. When fetal monitoring was performed, the results were normal. When the mother left the ENT clinic after the third visit, she was told to go to the ED or call 911 if she had another nosebleed, which she did not do. When she went to the ED with contractions, staff reacted to fetal distress and performed emergency cesarean delivery.
Verdict A Texas defense verdict was returned.
Difficult neonatal resuscitation: $8.4M
A nuchal cord was discovered at delivery. The child has cerebral palsy, a seizure disorder, and developmental delays. He cannot walk or talk, uses a feeding tube, and requires 24-hour care.
Parents’ claim Monitoring showed fetal distress for 5 hours, but the staff failed to perform a cesarean delivery or have a neonatal resuscitation team ready at delivery. After delivery, the baby was deprived of oxygen for 8 minutes before intubation. A back-up team should have been available.
Medical center’s defense Proper care was given. The resuscitation team was in a surgical suite.
Verdict An $8.4 million Georgia verdict was returned.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
In This Article
- Did OCs cause this woman’s stroke?
- Ureter injury not treated until the next day
- Patient didn’t want male physician
- Symptoms attributed to anesthesia: $2M
- Did nosebleeds cause baby’s disabilities?
- Difficult neonatal resuscitation: $8.4M
Still having reservations about ablation
“UPDATE ON ABNORMAL UTERINE BLEEDING”
HOWARD T. SHARP, MD (MARCH 2015)
Still having reservations about ablation
We discussed Dr. Sharp’s update on abnormal uterine bleeding (AUB) at a recent clinical meeting in my office. I have long told my nurse practition-ers that I am not in favor of ablation for AUB associated with ovulatory dysfunction (AUB-O). I learned from recent recertification reading that the risks for failure of ablation are dysmenorrhea, tubal ligation, and obesity, not anovulation. Therefore I may be more lenient with the use of ablation in this situation.
I still have the same reservations about performing ablation in women with ongoing irregular bleeding: If patients continue to have irregular bleeding, which they often do, it can be difficult to evaluate the endometrial cavity due to scarring, even at the time of dilation and curettage. Therefore, if they have other risk factors for hyperplasia or endometrial cancer or have postmenopausal bleeding, I won’t offer them ablation.
Nancy Shumeyko, MD
Binghamton, New York
Dr. Sharp responds
I appreciate Dr. Shumeyko’s comments and concerns about endometrial sampling in patients with abnormal bleeding (specifically AUB-O)who may have endometrial scarring after endometrial ablation. This is one of the unsettling challenges of post-ablation bleeding that we must sometimes address. Unfortunately, this can occur even in patients who seem to be “ideal” candidates for endometrial ablation (AUB-E). With amenorrhea rates generally less than 50% with most ablative methods, this unintended consequence makes the levonorgestrel IUD look all the more appealing. Hence, I agree with Dr. Shumeyko, and would add that just because we can do something, doesn’t mean we should.
The important question is how to repair the incision
I read with interest Dr. Barbieri’s March editorial about hysterotomy during cesarean delivery. In my opinion, the important question is not how to open but how to repair.
I cannot dictate or even encourage other surgeons to do as I do because our surgical skills differ. I create a bladder flap on primary cesarean sections out of habit, but I have performed a few without creating it, and without harming the patient.
Personally, I open the lower uterine segment sharply unless copious bleeding hampers my view. Most of the time, I can gain entrance to the uterine cavity without performing a concurrent amniotomy, which allows me to sharply perform the hysterotomy without concern for injuring the fetus. If bleeding hampers my view, I do all the dissection bluntly.
Have I noticed a big difference one way or the other? Not at all.
It is my impression that a double-layered closure is beneficial to the patient. I close the hysterotomy in this fashion even if the patient would not be a candidate for a trial of labor after cesarean in future pregnancies.
Maybe I am just lucky, but I only remember having injured 1 baby (a breech presentation fetus with severe oligohydramnios) since I finished my residency in 1986.
Tomas Hernandez, MD
Pasco, Washington
Dr. Barbieri responds
I respect Dr. Hernandez’s 30 years of clinical experience and appreciate his recommendations on opening and closing of the hysterotomy at cesarean delivery. My observation is that most US obstetricians close the hysterotomy in 2 layers. Like Dr. Hernandez, I favor a double-layer closure even if the patient is not a candidate for a trial of labor in a future pregnancy.
ANSWERING YOUR CODING QUESTIONS
A reader recently requested assistance for a specific coding challenge. We’ve asked our reimbursement specialist, Melanie Witt, RN, CPC, COBGC, MA, to provide her insight.
How should we code when using CUSA on vulvar dysplasia?
I provide coding assistance for several ObGyn practices and have always found your Web site to be informative. My question concerns Current Procedural Terminology (CPT) coding for removal of vulvar dysplasia using the cavitron ultrasonic surgical aspirator. The device is used to remove diseased epithelium. Generally, acetic acid is applied to highlight the diseased area and the lesions are removed with the device. The aspirator also collects the removed tissue so that it can be sent to pathology. Silver sulfadiazine cream is applied to the areas treated, as in laser surgery. The treatment may take 10 to 15 minutes. Which code, 56620 or 56515, should be used to reflect the actual work involved?
Marie D. Pelino, CPC
Annapolis, Maryland
Ms. Witt responds
The clinical vignette that was used by the CPT Editorial Panel in valuing code 56620 (Vulvectomy simple; partial) reads1:
The relative value units (RVUs) for this code are also fairly high at 14.86, and the procedure is designated as one that is performed in the hospital setting only. In addition, when valued, this procedure was assumed to represent 45 minutes of intraservice time (that is, the time for the actual surgery), and 56620 has a 90-day global period.
In contrast, 56515 (Destruction of lesion[s], vulva; extensive [eg, laser surgery, electrosurgery, cryosurgery, chemosurgery]) can be performed either in the facility or office setting and represents extensive destruction of tissue. In some cases, the physician may take a sample of tissue prior to the destruction, but this would be considered included in the destruction and not separately reportable, as the destruction represents the most extensive procedure. The clinical vignette used to value this code reads1:
The RVUs for this procedure are less at 5.75 in the facility setting and 6.45 in the office setting, but the intraservice time is also less than with 56620.
Given your description of the procedure in this case, I would consider 56515 to be the most correct code to report for this surgery.
Reference
1. American Medical Association. RBRVS DataManager Online. AMA Store Web site. https://commerce.ama-assn.org/store/catalog/productDetail.jsp?product_id=prod280002&navAction =push. Accessed March 17, 2015.
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
“UPDATE ON ABNORMAL UTERINE BLEEDING”
HOWARD T. SHARP, MD (MARCH 2015)
Still having reservations about ablation
We discussed Dr. Sharp’s update on abnormal uterine bleeding (AUB) at a recent clinical meeting in my office. I have long told my nurse practition-ers that I am not in favor of ablation for AUB associated with ovulatory dysfunction (AUB-O). I learned from recent recertification reading that the risks for failure of ablation are dysmenorrhea, tubal ligation, and obesity, not anovulation. Therefore I may be more lenient with the use of ablation in this situation.
I still have the same reservations about performing ablation in women with ongoing irregular bleeding: If patients continue to have irregular bleeding, which they often do, it can be difficult to evaluate the endometrial cavity due to scarring, even at the time of dilation and curettage. Therefore, if they have other risk factors for hyperplasia or endometrial cancer or have postmenopausal bleeding, I won’t offer them ablation.
Nancy Shumeyko, MD
Binghamton, New York
Dr. Sharp responds
I appreciate Dr. Shumeyko’s comments and concerns about endometrial sampling in patients with abnormal bleeding (specifically AUB-O)who may have endometrial scarring after endometrial ablation. This is one of the unsettling challenges of post-ablation bleeding that we must sometimes address. Unfortunately, this can occur even in patients who seem to be “ideal” candidates for endometrial ablation (AUB-E). With amenorrhea rates generally less than 50% with most ablative methods, this unintended consequence makes the levonorgestrel IUD look all the more appealing. Hence, I agree with Dr. Shumeyko, and would add that just because we can do something, doesn’t mean we should.
The important question is how to repair the incision
I read with interest Dr. Barbieri’s March editorial about hysterotomy during cesarean delivery. In my opinion, the important question is not how to open but how to repair.
I cannot dictate or even encourage other surgeons to do as I do because our surgical skills differ. I create a bladder flap on primary cesarean sections out of habit, but I have performed a few without creating it, and without harming the patient.
Personally, I open the lower uterine segment sharply unless copious bleeding hampers my view. Most of the time, I can gain entrance to the uterine cavity without performing a concurrent amniotomy, which allows me to sharply perform the hysterotomy without concern for injuring the fetus. If bleeding hampers my view, I do all the dissection bluntly.
Have I noticed a big difference one way or the other? Not at all.
It is my impression that a double-layered closure is beneficial to the patient. I close the hysterotomy in this fashion even if the patient would not be a candidate for a trial of labor after cesarean in future pregnancies.
Maybe I am just lucky, but I only remember having injured 1 baby (a breech presentation fetus with severe oligohydramnios) since I finished my residency in 1986.
Tomas Hernandez, MD
Pasco, Washington
Dr. Barbieri responds
I respect Dr. Hernandez’s 30 years of clinical experience and appreciate his recommendations on opening and closing of the hysterotomy at cesarean delivery. My observation is that most US obstetricians close the hysterotomy in 2 layers. Like Dr. Hernandez, I favor a double-layer closure even if the patient is not a candidate for a trial of labor in a future pregnancy.
ANSWERING YOUR CODING QUESTIONS
A reader recently requested assistance for a specific coding challenge. We’ve asked our reimbursement specialist, Melanie Witt, RN, CPC, COBGC, MA, to provide her insight.
How should we code when using CUSA on vulvar dysplasia?
I provide coding assistance for several ObGyn practices and have always found your Web site to be informative. My question concerns Current Procedural Terminology (CPT) coding for removal of vulvar dysplasia using the cavitron ultrasonic surgical aspirator. The device is used to remove diseased epithelium. Generally, acetic acid is applied to highlight the diseased area and the lesions are removed with the device. The aspirator also collects the removed tissue so that it can be sent to pathology. Silver sulfadiazine cream is applied to the areas treated, as in laser surgery. The treatment may take 10 to 15 minutes. Which code, 56620 or 56515, should be used to reflect the actual work involved?
Marie D. Pelino, CPC
Annapolis, Maryland
Ms. Witt responds
The clinical vignette that was used by the CPT Editorial Panel in valuing code 56620 (Vulvectomy simple; partial) reads1:
The relative value units (RVUs) for this code are also fairly high at 14.86, and the procedure is designated as one that is performed in the hospital setting only. In addition, when valued, this procedure was assumed to represent 45 minutes of intraservice time (that is, the time for the actual surgery), and 56620 has a 90-day global period.
In contrast, 56515 (Destruction of lesion[s], vulva; extensive [eg, laser surgery, electrosurgery, cryosurgery, chemosurgery]) can be performed either in the facility or office setting and represents extensive destruction of tissue. In some cases, the physician may take a sample of tissue prior to the destruction, but this would be considered included in the destruction and not separately reportable, as the destruction represents the most extensive procedure. The clinical vignette used to value this code reads1:
The RVUs for this procedure are less at 5.75 in the facility setting and 6.45 in the office setting, but the intraservice time is also less than with 56620.
Given your description of the procedure in this case, I would consider 56515 to be the most correct code to report for this surgery.
Reference
1. American Medical Association. RBRVS DataManager Online. AMA Store Web site. https://commerce.ama-assn.org/store/catalog/productDetail.jsp?product_id=prod280002&navAction =push. Accessed March 17, 2015.
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
“UPDATE ON ABNORMAL UTERINE BLEEDING”
HOWARD T. SHARP, MD (MARCH 2015)
Still having reservations about ablation
We discussed Dr. Sharp’s update on abnormal uterine bleeding (AUB) at a recent clinical meeting in my office. I have long told my nurse practition-ers that I am not in favor of ablation for AUB associated with ovulatory dysfunction (AUB-O). I learned from recent recertification reading that the risks for failure of ablation are dysmenorrhea, tubal ligation, and obesity, not anovulation. Therefore I may be more lenient with the use of ablation in this situation.
I still have the same reservations about performing ablation in women with ongoing irregular bleeding: If patients continue to have irregular bleeding, which they often do, it can be difficult to evaluate the endometrial cavity due to scarring, even at the time of dilation and curettage. Therefore, if they have other risk factors for hyperplasia or endometrial cancer or have postmenopausal bleeding, I won’t offer them ablation.
Nancy Shumeyko, MD
Binghamton, New York
Dr. Sharp responds
I appreciate Dr. Shumeyko’s comments and concerns about endometrial sampling in patients with abnormal bleeding (specifically AUB-O)who may have endometrial scarring after endometrial ablation. This is one of the unsettling challenges of post-ablation bleeding that we must sometimes address. Unfortunately, this can occur even in patients who seem to be “ideal” candidates for endometrial ablation (AUB-E). With amenorrhea rates generally less than 50% with most ablative methods, this unintended consequence makes the levonorgestrel IUD look all the more appealing. Hence, I agree with Dr. Shumeyko, and would add that just because we can do something, doesn’t mean we should.
The important question is how to repair the incision
I read with interest Dr. Barbieri’s March editorial about hysterotomy during cesarean delivery. In my opinion, the important question is not how to open but how to repair.
I cannot dictate or even encourage other surgeons to do as I do because our surgical skills differ. I create a bladder flap on primary cesarean sections out of habit, but I have performed a few without creating it, and without harming the patient.
Personally, I open the lower uterine segment sharply unless copious bleeding hampers my view. Most of the time, I can gain entrance to the uterine cavity without performing a concurrent amniotomy, which allows me to sharply perform the hysterotomy without concern for injuring the fetus. If bleeding hampers my view, I do all the dissection bluntly.
Have I noticed a big difference one way or the other? Not at all.
It is my impression that a double-layered closure is beneficial to the patient. I close the hysterotomy in this fashion even if the patient would not be a candidate for a trial of labor after cesarean in future pregnancies.
Maybe I am just lucky, but I only remember having injured 1 baby (a breech presentation fetus with severe oligohydramnios) since I finished my residency in 1986.
Tomas Hernandez, MD
Pasco, Washington
Dr. Barbieri responds
I respect Dr. Hernandez’s 30 years of clinical experience and appreciate his recommendations on opening and closing of the hysterotomy at cesarean delivery. My observation is that most US obstetricians close the hysterotomy in 2 layers. Like Dr. Hernandez, I favor a double-layer closure even if the patient is not a candidate for a trial of labor in a future pregnancy.
ANSWERING YOUR CODING QUESTIONS
A reader recently requested assistance for a specific coding challenge. We’ve asked our reimbursement specialist, Melanie Witt, RN, CPC, COBGC, MA, to provide her insight.
How should we code when using CUSA on vulvar dysplasia?
I provide coding assistance for several ObGyn practices and have always found your Web site to be informative. My question concerns Current Procedural Terminology (CPT) coding for removal of vulvar dysplasia using the cavitron ultrasonic surgical aspirator. The device is used to remove diseased epithelium. Generally, acetic acid is applied to highlight the diseased area and the lesions are removed with the device. The aspirator also collects the removed tissue so that it can be sent to pathology. Silver sulfadiazine cream is applied to the areas treated, as in laser surgery. The treatment may take 10 to 15 minutes. Which code, 56620 or 56515, should be used to reflect the actual work involved?
Marie D. Pelino, CPC
Annapolis, Maryland
Ms. Witt responds
The clinical vignette that was used by the CPT Editorial Panel in valuing code 56620 (Vulvectomy simple; partial) reads1:
The relative value units (RVUs) for this code are also fairly high at 14.86, and the procedure is designated as one that is performed in the hospital setting only. In addition, when valued, this procedure was assumed to represent 45 minutes of intraservice time (that is, the time for the actual surgery), and 56620 has a 90-day global period.
In contrast, 56515 (Destruction of lesion[s], vulva; extensive [eg, laser surgery, electrosurgery, cryosurgery, chemosurgery]) can be performed either in the facility or office setting and represents extensive destruction of tissue. In some cases, the physician may take a sample of tissue prior to the destruction, but this would be considered included in the destruction and not separately reportable, as the destruction represents the most extensive procedure. The clinical vignette used to value this code reads1:
The RVUs for this procedure are less at 5.75 in the facility setting and 6.45 in the office setting, but the intraservice time is also less than with 56620.
Given your description of the procedure in this case, I would consider 56515 to be the most correct code to report for this surgery.
Reference
1. American Medical Association. RBRVS DataManager Online. AMA Store Web site. https://commerce.ama-assn.org/store/catalog/productDetail.jsp?product_id=prod280002&navAction =push. Accessed March 17, 2015.
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
LANDMARK STUDY: Cell-Free DNA Analysis for Down Syndrome Screening in the General Pregnancy Population
Click here to download the PDF.
To date, cell-free DNA (cfDNA) screening for fetal trisomy has been offered primarily to women at increased risk for fetal aneuploidy, but not to the general pregnancy population. Recently, the results of a large, prospective, multicenter, blinded study were published, demonstrating that the Harmony test for risk assessment of trisomy 21 (Down Syndrome) outperforms combined first trimester screening in the general pregnancy population. This supplement examines the crucial findings of cfDNA analysis for Down syndrome screening in the general pregnancy population using the Harmony test.
The Harmony Prenatal Test is developed by Ariosa Diagnostics. Ariosa Diagnostics is a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). As with other laboratory-developed tests, this testing service has not been cleared or approved by the US FDA or any other federal regulatory agencies. Non-invasive prenatal testing (NIPT) services based on cell-free DNA analyses are not diagnostic; high-risk results should be confirmed by diagnostic testing. Data have not been submitted to or evaluated by Federal regulatory agencies and the test is not for sale as an In Vitro Diagnostic (IVD) in the US or the EU.
To view an exclusive video on the pivotal findings discussed in this supplement, click here.
Click here to download the PDF.
To date, cell-free DNA (cfDNA) screening for fetal trisomy has been offered primarily to women at increased risk for fetal aneuploidy, but not to the general pregnancy population. Recently, the results of a large, prospective, multicenter, blinded study were published, demonstrating that the Harmony test for risk assessment of trisomy 21 (Down Syndrome) outperforms combined first trimester screening in the general pregnancy population. This supplement examines the crucial findings of cfDNA analysis for Down syndrome screening in the general pregnancy population using the Harmony test.
The Harmony Prenatal Test is developed by Ariosa Diagnostics. Ariosa Diagnostics is a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). As with other laboratory-developed tests, this testing service has not been cleared or approved by the US FDA or any other federal regulatory agencies. Non-invasive prenatal testing (NIPT) services based on cell-free DNA analyses are not diagnostic; high-risk results should be confirmed by diagnostic testing. Data have not been submitted to or evaluated by Federal regulatory agencies and the test is not for sale as an In Vitro Diagnostic (IVD) in the US or the EU.
To view an exclusive video on the pivotal findings discussed in this supplement, click here.
Click here to download the PDF.
To date, cell-free DNA (cfDNA) screening for fetal trisomy has been offered primarily to women at increased risk for fetal aneuploidy, but not to the general pregnancy population. Recently, the results of a large, prospective, multicenter, blinded study were published, demonstrating that the Harmony test for risk assessment of trisomy 21 (Down Syndrome) outperforms combined first trimester screening in the general pregnancy population. This supplement examines the crucial findings of cfDNA analysis for Down syndrome screening in the general pregnancy population using the Harmony test.
The Harmony Prenatal Test is developed by Ariosa Diagnostics. Ariosa Diagnostics is a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). As with other laboratory-developed tests, this testing service has not been cleared or approved by the US FDA or any other federal regulatory agencies. Non-invasive prenatal testing (NIPT) services based on cell-free DNA analyses are not diagnostic; high-risk results should be confirmed by diagnostic testing. Data have not been submitted to or evaluated by Federal regulatory agencies and the test is not for sale as an In Vitro Diagnostic (IVD) in the US or the EU.
To view an exclusive video on the pivotal findings discussed in this supplement, click here.
Imaging the endometrioma and mature cystic teratoma
The preferred imaging method to evaluate the majority of adnexal cysts is ultrasonography, which can help characterize the cyst type. Common benign adnexal cyst types include simple, hemorrhagic, endometrioma, and mature teratoma (dermoid cyst). In this part 2 of a 4-part series on cystic adnexal pathology, we focus on imaging signs for, and follow-up of, endometriomas and mature teratomas.
Endometriomas
Endometriomas are common, typically benign, cysts that produce homogenous, low-level internal echoes and a “ground glass” appearance on ultrasonography. No internal flow is apparent on color Doppler. The presence of tiny echogenic wall foci can distinguish an endometrioma from a hemorrhagic cyst.
Rarely, endometriomas may undergo malignant transformation. Usually this occurs with cysts greater than 9 cm and in patients aged 45 years or older. A malignancy often exhibits rapid growth or the development of a solid nodule with flow on color Doppler.
Management
Although surgery remains the first-line management for women with symptomatic or enlarging endometriomas, there appears to be a role for sonographic observation, with continuous progestational treatment, in women with small (< 5 cm) asymptomatic endometriomas.
The Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended1:
- Short-interval follow-up (6 to 12 weeks) in reproductive-aged women to ensure acute hemorrhagic cysts are not mistaken for endometriomas
- If not removed surgically, sonographic follow-up is recommended, with frequency of follow up based on patient age and symptoms and cyst size and characteristics.
In FIGURES 1 through 11 (slides of image collections), we present several cases, including one of a 25-year-old patient presenting with pelvic pain and dyspareunia who was later found to have bilateral endometriomas.
Mature teratomas
Mature cystic teratomas display several telltale signs on imaging, including:
- hyperechoic lines/dots (“dermoid mesh”) corresponding to hair/skeletal components
- “Rokitanski nodule” – a peripherally placed mass of sebum, bones, and hair
- posterior acoustic shadowing
- cystic or floating spherical structures
- no internal flow on color Doppler
Rarely, dermoid cysts may undergo malignant transformation. Usually this occurs in cysts greater than 10 cm and in patients aged 50 years or older. Internal flow on color Doppler, branching, or invasion into adjacent structures can indicate malignancy.
Management
The traditional treatment for dermoid cysts is surgical. However, given the ability for accurate diagnosis with vaginal ultrasonography, there appears to be a role for sonographic observation in asymptomatic women with small dermoids.2
If the cyst is not surgically removed, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended initial sonographic follow up at no more than 6 months to 1 year to ensure no change in size or internal architecture.1
In FIGURES 12 through 24 below (slides of image collections), we offer imaging from the case presentation and follow-up of a 19-year-old patient with pelvic pain who has a history of ovarian cystectomy for dermoid cyst, as well as 6 additional case illustrations.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Levine D, Brown DL, Andreotti RF, et al. Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology. 2010;256(3):943–954.
2. Hoo WL, Yazbek WL, Holland T, Mavrelos D, Tong EN, Jurkovic D. Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome? Ultrasound Obstet Gynecol. 2010;36(2): 235–240.
The preferred imaging method to evaluate the majority of adnexal cysts is ultrasonography, which can help characterize the cyst type. Common benign adnexal cyst types include simple, hemorrhagic, endometrioma, and mature teratoma (dermoid cyst). In this part 2 of a 4-part series on cystic adnexal pathology, we focus on imaging signs for, and follow-up of, endometriomas and mature teratomas.
Endometriomas
Endometriomas are common, typically benign, cysts that produce homogenous, low-level internal echoes and a “ground glass” appearance on ultrasonography. No internal flow is apparent on color Doppler. The presence of tiny echogenic wall foci can distinguish an endometrioma from a hemorrhagic cyst.
Rarely, endometriomas may undergo malignant transformation. Usually this occurs with cysts greater than 9 cm and in patients aged 45 years or older. A malignancy often exhibits rapid growth or the development of a solid nodule with flow on color Doppler.
Management
Although surgery remains the first-line management for women with symptomatic or enlarging endometriomas, there appears to be a role for sonographic observation, with continuous progestational treatment, in women with small (< 5 cm) asymptomatic endometriomas.
The Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended1:
- Short-interval follow-up (6 to 12 weeks) in reproductive-aged women to ensure acute hemorrhagic cysts are not mistaken for endometriomas
- If not removed surgically, sonographic follow-up is recommended, with frequency of follow up based on patient age and symptoms and cyst size and characteristics.
In FIGURES 1 through 11 (slides of image collections), we present several cases, including one of a 25-year-old patient presenting with pelvic pain and dyspareunia who was later found to have bilateral endometriomas.
Mature teratomas
Mature cystic teratomas display several telltale signs on imaging, including:
- hyperechoic lines/dots (“dermoid mesh”) corresponding to hair/skeletal components
- “Rokitanski nodule” – a peripherally placed mass of sebum, bones, and hair
- posterior acoustic shadowing
- cystic or floating spherical structures
- no internal flow on color Doppler
Rarely, dermoid cysts may undergo malignant transformation. Usually this occurs in cysts greater than 10 cm and in patients aged 50 years or older. Internal flow on color Doppler, branching, or invasion into adjacent structures can indicate malignancy.
Management
The traditional treatment for dermoid cysts is surgical. However, given the ability for accurate diagnosis with vaginal ultrasonography, there appears to be a role for sonographic observation in asymptomatic women with small dermoids.2
If the cyst is not surgically removed, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended initial sonographic follow up at no more than 6 months to 1 year to ensure no change in size or internal architecture.1
In FIGURES 12 through 24 below (slides of image collections), we offer imaging from the case presentation and follow-up of a 19-year-old patient with pelvic pain who has a history of ovarian cystectomy for dermoid cyst, as well as 6 additional case illustrations.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
The preferred imaging method to evaluate the majority of adnexal cysts is ultrasonography, which can help characterize the cyst type. Common benign adnexal cyst types include simple, hemorrhagic, endometrioma, and mature teratoma (dermoid cyst). In this part 2 of a 4-part series on cystic adnexal pathology, we focus on imaging signs for, and follow-up of, endometriomas and mature teratomas.
Endometriomas
Endometriomas are common, typically benign, cysts that produce homogenous, low-level internal echoes and a “ground glass” appearance on ultrasonography. No internal flow is apparent on color Doppler. The presence of tiny echogenic wall foci can distinguish an endometrioma from a hemorrhagic cyst.
Rarely, endometriomas may undergo malignant transformation. Usually this occurs with cysts greater than 9 cm and in patients aged 45 years or older. A malignancy often exhibits rapid growth or the development of a solid nodule with flow on color Doppler.
Management
Although surgery remains the first-line management for women with symptomatic or enlarging endometriomas, there appears to be a role for sonographic observation, with continuous progestational treatment, in women with small (< 5 cm) asymptomatic endometriomas.
The Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended1:
- Short-interval follow-up (6 to 12 weeks) in reproductive-aged women to ensure acute hemorrhagic cysts are not mistaken for endometriomas
- If not removed surgically, sonographic follow-up is recommended, with frequency of follow up based on patient age and symptoms and cyst size and characteristics.
In FIGURES 1 through 11 (slides of image collections), we present several cases, including one of a 25-year-old patient presenting with pelvic pain and dyspareunia who was later found to have bilateral endometriomas.
Mature teratomas
Mature cystic teratomas display several telltale signs on imaging, including:
- hyperechoic lines/dots (“dermoid mesh”) corresponding to hair/skeletal components
- “Rokitanski nodule” – a peripherally placed mass of sebum, bones, and hair
- posterior acoustic shadowing
- cystic or floating spherical structures
- no internal flow on color Doppler
Rarely, dermoid cysts may undergo malignant transformation. Usually this occurs in cysts greater than 10 cm and in patients aged 50 years or older. Internal flow on color Doppler, branching, or invasion into adjacent structures can indicate malignancy.
Management
The traditional treatment for dermoid cysts is surgical. However, given the ability for accurate diagnosis with vaginal ultrasonography, there appears to be a role for sonographic observation in asymptomatic women with small dermoids.2
If the cyst is not surgically removed, the Society of Radiologists in Ultrasound 2010 Consensus Conference Statement recommended initial sonographic follow up at no more than 6 months to 1 year to ensure no change in size or internal architecture.1
In FIGURES 12 through 24 below (slides of image collections), we offer imaging from the case presentation and follow-up of a 19-year-old patient with pelvic pain who has a history of ovarian cystectomy for dermoid cyst, as well as 6 additional case illustrations.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14
Figure 15
Figure 16
Figure 17
Figure 18
Figure 19
Figure 20
Figure 21
Figure 22
Figure 23
Figure 24
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Levine D, Brown DL, Andreotti RF, et al. Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology. 2010;256(3):943–954.
2. Hoo WL, Yazbek WL, Holland T, Mavrelos D, Tong EN, Jurkovic D. Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome? Ultrasound Obstet Gynecol. 2010;36(2): 235–240.
1. Levine D, Brown DL, Andreotti RF, et al. Management of asymptomatic ovarian and other adnexal cysts imaged at US: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology. 2010;256(3):943–954.
2. Hoo WL, Yazbek WL, Holland T, Mavrelos D, Tong EN, Jurkovic D. Expectant management of ultrasonically diagnosed ovarian dermoid cysts: is it possible to predict outcome? Ultrasound Obstet Gynecol. 2010;36(2): 235–240.
Uterus transplantation: Medical breakthrough or surgical folly?
Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.
Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?
In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.1 Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.
The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?
The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.5,6
The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.
After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.
Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.
A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.
Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.
Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.
Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.
In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.10 This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.
The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.
Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.
“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.14 His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.
In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.
A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.
Share your thoughts on this article! Send your Letter to the Editor to Please include your name and the city and state in which you practice.
Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Brännström M, Johannesson L, Bokstrom H, et al. Livebirth after uterus transplantation. Lancet. 2015;385(9968):607–616.
2. Johannesson L, Enskog A, Mölne J, et al. Preclinical report on allogeneic uterus transplantation in nonhuman primates. Hum Reprod. 2013;28(1):189–198.
3. Brännström M, Diaz-Garcia C, Hanafy A, Olausson M, Tzakis A. Uterus transplantation: animal research and human possibilities. Fertil Steril. 2012;97(6):1269–1276.
4. Brännström M, Wranning CA, Altchek A. Experimental uterus transplantation. Hum Reprod Update. 2010;16(3):329–345.
5. Brännström M, Johannesson L, Dahm-Kähler P, et al. First clinical uterus transplant trial: a six-month report. Fertil Steril. 2014;101(5):1228–1236.
6. Johannesson L, Kvarnstrom N, Mölne J, et al. Uterus transplantation trial: 1-year outcome. Fertil Steril. 2015;103(1):199–204.
7. Concepcion BP, Schaefer HM. Caring for the pregnant kidney transplant recipient. Clin Transplant. 2011;25(6):821–829.
8. Rupley DM, Janda AM, Kapeles SR, Wilson TM, Berman D, Mathur AK. Preconception counseling, fertility and pregnancy complications after abdominal organ transplantation: a survey and cohort study of 532 recipients. Clin Transplant. 2014;28(9):937–945.
9. McKay DB, Josephson MA. Pregnancy in recipients of solid organs—effects on mother and child. N Engl J Med. 2006;354(12):1281–1293.
10. Metcalfe J, Romney SL, Ramsey LH, Reid DH, Burwell CS. Estimation of uterine blood flow in normal human pregnancy at term. J Clin Invest. 1955;34(11):1632–1638.
11. Olausson M, Johannesson L, Brattgård D, et al. Ethics of uterus transplantation with live donors. Fertil Steril. 2014;102(1):40–43.
12. Del Priore G, Saso S, Meslin EM, et al. Uterine transplantation—a real possibility? The Indianapolis consensus. Hum Reprod. 2013;28(2):288–291.
13. Brosens I, Ghaem-Maghami S, Pijnenborg R. Uterus transplantation in the human: a complex surgical, medical and ethical challenge. Human Reprod. 2013;28(2):292–293.
14. Desai SP, Desai MS, Wood DN, Maddi R, Leeson S, Tilney NL. A semi-centennial report on the participants depicted in Joel Babb’s portrait, “The First Successful Kidney Transplantation”. Am J Transplant. 2007;7(7):1683–1688.
Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.
Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?
In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.1 Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.
The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?
The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.5,6
The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.
After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.
Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.
A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.
Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.
Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.
Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.
In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.10 This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.
The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.
Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.
“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.14 His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.
In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.
A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.
Share your thoughts on this article! Send your Letter to the Editor to Please include your name and the city and state in which you practice.
Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.
Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?
In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.1 Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.
The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?
The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.5,6
The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.
After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.
Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.
A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.
Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.
Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.
Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts.7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.
In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute.10 This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.
The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.
Ethics. Uterus transplantation raises many bioethical concerns and programs need to engage biomedical ethicists to guide their activities.11–13 Careful attention to thorough informed consent, risk-benefit analysis, equitable access, and fair selection of participants will be critical to running an ethical program. To reduce the risks of the procedure, programs likely will explore the use of uteri obtained from women who are brain dead or cadavers to spare altruistic living donors from undergoing hysterectomy surgery.
“Group of fools” or Nobel Prize in wait?
On December 23, 1954, the first successful kidney transplant was performed by Dr. Joseph E. Murray and his team at the Peter Bent Brigham Hospital, a predecessor to the Brigham and Women’s Hospital.14 His small group of physicians worked for years to perfect the kidney transplantation technique in the laboratory prior to attempting the case. A key to their success was the decision to perform the transplant with identical twins as the donor and recipient.
In the 1950s there was great controversy about whether kidney transplantation was a medical breakthrough or surgical folly. The lead surgical team was referred to as the “group of fools” by some colleagues. But Dr. Murray and his team succeeded in their efforts and opened the field of solid organ transplant. Recognizing the importance of his accomplishment, the Nobel Prize Committee awarded Dr. Murray the 1990 Nobel Prize in Physiology or Medicine. Dr. E. Donnell Thomas, a co-recipient of the award, was simultaneously recognized for developing bone marrow transplantation as a treatment for leukemia.
A medical breakthrough…
Organ transplantation medicine initially focused on the treatment of life-threatening diseases, including kidney, heart, lung, and liver failure. With recent innovations in composite tissue transplants, including face and limb, transplantation medicine is evolving to expand its focus to the repair of functional deficits that are not life threatening but do significantly impact quality of life. Uterus transplantation is an example of the new era of using transplants to repair functional deficits. The clinicians and patients involved in these innovative programs are courageous pioneers opening new vistas and helping to realize previously impossible dreams. In our time, many stakeholders are likely to conclude that uterus transplantation is a surgical folly. However, I predict that our children will conclude that uterus transplantation represents a medical breakthrough.
Share your thoughts on this article! Send your Letter to the Editor to Please include your name and the city and state in which you practice.
Weigh in at the Quick Poll on the homepage. Send your answers to these cases and any comments to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Brännström M, Johannesson L, Bokstrom H, et al. Livebirth after uterus transplantation. Lancet. 2015;385(9968):607–616.
2. Johannesson L, Enskog A, Mölne J, et al. Preclinical report on allogeneic uterus transplantation in nonhuman primates. Hum Reprod. 2013;28(1):189–198.
3. Brännström M, Diaz-Garcia C, Hanafy A, Olausson M, Tzakis A. Uterus transplantation: animal research and human possibilities. Fertil Steril. 2012;97(6):1269–1276.
4. Brännström M, Wranning CA, Altchek A. Experimental uterus transplantation. Hum Reprod Update. 2010;16(3):329–345.
5. Brännström M, Johannesson L, Dahm-Kähler P, et al. First clinical uterus transplant trial: a six-month report. Fertil Steril. 2014;101(5):1228–1236.
6. Johannesson L, Kvarnstrom N, Mölne J, et al. Uterus transplantation trial: 1-year outcome. Fertil Steril. 2015;103(1):199–204.
7. Concepcion BP, Schaefer HM. Caring for the pregnant kidney transplant recipient. Clin Transplant. 2011;25(6):821–829.
8. Rupley DM, Janda AM, Kapeles SR, Wilson TM, Berman D, Mathur AK. Preconception counseling, fertility and pregnancy complications after abdominal organ transplantation: a survey and cohort study of 532 recipients. Clin Transplant. 2014;28(9):937–945.
9. McKay DB, Josephson MA. Pregnancy in recipients of solid organs—effects on mother and child. N Engl J Med. 2006;354(12):1281–1293.
10. Metcalfe J, Romney SL, Ramsey LH, Reid DH, Burwell CS. Estimation of uterine blood flow in normal human pregnancy at term. J Clin Invest. 1955;34(11):1632–1638.
11. Olausson M, Johannesson L, Brattgård D, et al. Ethics of uterus transplantation with live donors. Fertil Steril. 2014;102(1):40–43.
12. Del Priore G, Saso S, Meslin EM, et al. Uterine transplantation—a real possibility? The Indianapolis consensus. Hum Reprod. 2013;28(2):288–291.
13. Brosens I, Ghaem-Maghami S, Pijnenborg R. Uterus transplantation in the human: a complex surgical, medical and ethical challenge. Human Reprod. 2013;28(2):292–293.
14. Desai SP, Desai MS, Wood DN, Maddi R, Leeson S, Tilney NL. A semi-centennial report on the participants depicted in Joel Babb’s portrait, “The First Successful Kidney Transplantation”. Am J Transplant. 2007;7(7):1683–1688.
1. Brännström M, Johannesson L, Bokstrom H, et al. Livebirth after uterus transplantation. Lancet. 2015;385(9968):607–616.
2. Johannesson L, Enskog A, Mölne J, et al. Preclinical report on allogeneic uterus transplantation in nonhuman primates. Hum Reprod. 2013;28(1):189–198.
3. Brännström M, Diaz-Garcia C, Hanafy A, Olausson M, Tzakis A. Uterus transplantation: animal research and human possibilities. Fertil Steril. 2012;97(6):1269–1276.
4. Brännström M, Wranning CA, Altchek A. Experimental uterus transplantation. Hum Reprod Update. 2010;16(3):329–345.
5. Brännström M, Johannesson L, Dahm-Kähler P, et al. First clinical uterus transplant trial: a six-month report. Fertil Steril. 2014;101(5):1228–1236.
6. Johannesson L, Kvarnstrom N, Mölne J, et al. Uterus transplantation trial: 1-year outcome. Fertil Steril. 2015;103(1):199–204.
7. Concepcion BP, Schaefer HM. Caring for the pregnant kidney transplant recipient. Clin Transplant. 2011;25(6):821–829.
8. Rupley DM, Janda AM, Kapeles SR, Wilson TM, Berman D, Mathur AK. Preconception counseling, fertility and pregnancy complications after abdominal organ transplantation: a survey and cohort study of 532 recipients. Clin Transplant. 2014;28(9):937–945.
9. McKay DB, Josephson MA. Pregnancy in recipients of solid organs—effects on mother and child. N Engl J Med. 2006;354(12):1281–1293.
10. Metcalfe J, Romney SL, Ramsey LH, Reid DH, Burwell CS. Estimation of uterine blood flow in normal human pregnancy at term. J Clin Invest. 1955;34(11):1632–1638.
11. Olausson M, Johannesson L, Brattgård D, et al. Ethics of uterus transplantation with live donors. Fertil Steril. 2014;102(1):40–43.
12. Del Priore G, Saso S, Meslin EM, et al. Uterine transplantation—a real possibility? The Indianapolis consensus. Hum Reprod. 2013;28(2):288–291.
13. Brosens I, Ghaem-Maghami S, Pijnenborg R. Uterus transplantation in the human: a complex surgical, medical and ethical challenge. Human Reprod. 2013;28(2):292–293.
14. Desai SP, Desai MS, Wood DN, Maddi R, Leeson S, Tilney NL. A semi-centennial report on the participants depicted in Joel Babb’s portrait, “The First Successful Kidney Transplantation”. Am J Transplant. 2007;7(7):1683–1688.
Endometriosis: Expert answers to 7 crucial questions on diagnosis
CASE Is her chronic pelvic pain caused by endometriosis?
M.L. is a 32-year-old nulliparous woman who is referred to your office by her primary care provider for chronic pelvic pain. She reports severe dysmenorrhea as her main symptom, but she also mentions dyspareunia. She says these symptoms have been present for several years but have increased in intensity gradually. She asks what you consider to be the most likely diagnosis.
What potential diagnoses do you mention to her? And how do you identify the cause of her pain?
Although endometriosis—the presence of endometrial tissue outside the uterus—affects at least 5 million women of reproductive age in the United States alone, it can be a challenging diagnosis for several reasons.
“Endometriosis is a great masquerader,” says Linda Giudice, MD, PhD. “It presents with a variety of pain patterns, intensities, and triggers. It can also involve symptoms that overlap those of other disorders, including disorders of the gastrointestinal and urinary tracts.”
Although endometriosis falls within the differential diagnosis of chronic pelvic pain, “it is usually not high on the list in the primary care setting (adult and adolescent),” Dr. Giudice adds. She is the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
John R. Lue, MD, MPH, an author of the most recent practice bulletin on endometriosis from the American College of Obstetricians and Gynecologists,1 sees the situation similarly.
“The main challenge in the diagnosis of endometriosis is that its presentation mimics other causes of chronic pelvic pain,” he says. “Pelvic pain due to endometriosis is usually chronic (lasting ≥6 months). It is associated with dysmenorrhea in 50% to 90% of cases, as well as with dyspareunia, deep pelvic pain, and lower abdominal pain with or without back and loin pain. The pain can occur unpredictably and intermittently throughout the menstrual cycle or it can be continuous. In addition, it can be dull, throbbing, or sharp and may be exacerbated by physical activity.2,3 Up to 20% of women with endometriosis have concurrent pain conditions.”4 Dr. Lue is associate professor, chief of the section of general obstetrics and gynecology, and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
Among other diseases of the female pelvis that have relatively similar presentation, Dr. Lue adds, are pathologies of the:
- uterus (adenomyosis, fibroids)
- fallopian tube (hydrosalpinx)
- ovaries (ovarian cysts)
- bladder (interstitial cystitis)
- bowel (irritable bowel syndrome)
- musculoskeletal system (piriformis syndrome).
Before pelvic pain is attributed to endometriosis, he says, the provider should rule out bowel, bladder, musculoskeletal, and psychiatric causes.
This article focuses on 7 questions, the answers of which are critical to narrowing in on the diagnosis of endometriosis, including essential factors to consider in the patient history, imaging and other diagnostic tools, and considerations in surgical exploration. In the second and third installments of this in-depth series on endometriosis, pain and infertility will be the respective subjects of investigation.
Several theories explain the “why” of endometriosis
A dominant theory is that peritoneal endometrial implants arise from retrograde menstruation, during which endometrial tissue passes through the fallopian tubes into the pelvis, says John R. Lue, MD, MPH. Dr. Lue is associate professor and chief of the section of general obstetrics and gynecology and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
“Additional theories include immune dysfunction that interferes with clearing of endometrial lesions in the pelvis, as well as genetic alterations that lead to growth dysregulation,” he says.1 “These theories all have merit, and it is likely that the pathogenesis of endometriosis is multifactorial.”
Another strong theory involves the homeobox (HOX) genes, “which mediate embryonic development,” says Dr. Lue.2,3 “These genes are translated into transcription factors that regulate downstream genes necessary for growth and differentiation. It has been demonstrated that HOX genes play an analogous role in endometrial development during the adult menstrual cycle.4 HOX gene expression regulates the growth and development of the human endometrium.5 The expression of HOX genes A10 and A11 varies in response to sex steroids during the menstrual cycle, with dramatic upregulation in the mid-secretory phase,” says Dr. Lue. Recent studies suggest that these genes “play a major role” in endometriosis.6
“Since ovarian endometriomas are clonal and lesions usually have genetic mutations, such somatic mutations with subsequent growth dysregulation may also be etiologic factors,” says Dr. Lue.1,7,8 “Disease at distant sites may be caused by lymphatic or hematogenous spread or metaplastic transformation.”
References
1. Giudice LC, Swierz LM, Burney RO. Edometriosis. In: Jameson JL, DeGroot LJ, eds. Endocrinology. 6th ed. New York, NY: Elsevier; 2010:2356–2370.
2. Krumlauf R. Hox genes in vertebrate development. Cell. 1992;78(2):191–201.
3. McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283–302.
4. Taylor H, Igarashi P, Olive D, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999;84(3):1129–1135.
5. Taylor H, Vanden Heuvel GB, Igarashi P. A conserved HOX axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the HOXA cluster genes. Biol Reprod. 1997;57(6):1338–1345.
6. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
7. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269.
8. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
1. Why such a long delay in diagnosis?
Investigators exploring the length of time between a patient’s presentation with symptoms and diagnosis have found it to be particularly long for endometriosis, ranging from 6 to 11 years.
Because endometriosis is usually not high on the list of differential diagnoses for chronic pelvic pain in the primary care setting, a patient may not be referred to a gynecologist unless those symptoms include severe dysmenorrhea, dyspareunia, or similar findings. Once the referral is made, the gynecologist “will usually try contraceptive steroids, nonsteroidal anti-inflammatory drugs, or second-line progestins before a diagnosis is made,” says Dr. Giudice.5
The delay in diagnosis “is astounding,” she adds, “and has its roots in empiric medical therapies and a combination of patients fearing a diagnosis of cancer and reluctance of gynecologists to perform laparoscopy on adolescents.”6
Another possible cause of diagnostic delay: Some adolescent girls may not realize when their pain is severe. Because they may have always experienced a high degree of pain since menarche, they may assume it to be a normal aspect of womanhood and delay seeking help, says Pamela Stratton, MD, chief of the gynecology consult service at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
2. Have any biomarkers proved to be useful diagnostic tools?
Any biomarker proven to reliably identify endometriosis would be a boon to medicine, as it would provide a noninvasive or minimally invasive alternative to diagnostic laparoscopy, the current gold standard. Regrettably, the search for such a biomarker has produced “disappointing results,” says Dr. Giudice.
“Recent systematic reviews of all proposed endometriosis-related biomarkers over the last 25 years in serum, plasma, urine, and endometrium could not identify an unequivocally clinically useful biomarker or panel of biomarkers,” she notes.7,8 “This is due mainly to low numbers of subjects, small populations for validations, cycle/hormonal- and disease stage-dependence, poorly defined controls, and low sensitivity and specificity.”
One hopeful development: “Whole genome transcriptomics of archived endometrial tissue and machine learning found several classifiers to diagnose and stage endometriosis with high accuracy that were validated on an independent sample set,” says Dr. Giudice.9 “However, these data now warrant a prospective, multisite study for further validation.”
Environmental factors, estrogen, and endometriosis
“There is increasing evidence that in utero and also adult exposures to endocrine-disrupting chemicals (EDCs) play a role in the pathogenesis and progression of disease,” says Linda Giudice, MD, PhD, the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
“For example, the Nurses’ Health Study II, a prospective cohort study of more than 80,000 women, revealed that daughters exposed to diethylstilbestrol (DES) had an 80% increased risk (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.8) of developing endometriosis,” she says.1
“Also, dioxin (TCDD) exposure in rats in utero on gestational day 8 increased the size of endometriosis lesions when combined with an adult exposure,” Dr. Giudice says.2 Although we do not know the precise mechanisms underlying in utero events that result in disease onset as a teen or adult, abnormal programming of the female reproductive tract by EDCs and similar agents is believed to play a role, she says.3
Because estrogen is essential for endometriosis lesions and associated symptoms to progress, “EDCs that have either estrogenic activity or interfere with estrogen metabolism or action, or both, have been proposed as contributors to progression of disease. Abundant animal data using nonhuman primate and rodent models and exposures to organochlorines and other EDCs support this hypothesis,” Dr. Giudice says.4
“The weight of human evidence of associations of EDCs and the risk of endometriosis in adult women depends on the class of endocrine disrupter,” Dr. Giudice continues. “Strongest correlations are with polychlorobiphenyls (PCBs), where 10 of 12 studies found significant odds of disease and circulating or omental fat concentrations of these compounds. PCBs inhibit peripheral natural killer cell activity and interleukin 1b and 12 production, relevant to the immune component of endometriosis progression.”
“Significant risk has also been associated with organochlorines (in three of three studies) and perfluorochemicals. In contrast, data linking endometriosis with exposures to dioxins, phthalates, and bisphenol A are equivocal, with some studies finding significant odds ratios and others failing to find significant correlations. Interestingly, dioxins have a significant association with deep infiltrating endometriotic lesions.”5
References
1. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Michels KB, Hunter DJ. In utero exposures and the incidence of endometriosis. Fertil Steril. 2004;82(6):1501–1508.
2. Cummings AM, Hedge JM, Birnbaum LS. Effects on prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice. Toxicol Sci. 1999;52(1):45–49.
3. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
4. Crain DA, Janssen SJ, Edwards TM, et al. Female reproductive disorders: the roles of endocrine disrupting compounds and developmental timing. Fertil Steril. 2008;90(4):911–940.
5. Heilier JF, Donnez J, Nackers F, et al. Environmental and host-associated risk factors in endometriosis and deep endometriotic nodules: a matched case-control study. Environ Res. 2007;103(1):121–129.
3. What aspects of the patient history are key?
Dr. Stratton recommends that clinicians begin their evaluation of the patient with pain by asking her to describe that pain—how long she has had it, when it occurs, and which areas are affected.
“Most women with endometriosis-associated pain have chronic pelvic pain,” Dr. Stratton continues.5 “Up to 90% of those have dysmenorrhea or cyclic pain with menses.”10 In addition, women with endometriosis “commonly report having pain with any bleeding or spotting. About 30% of women diagnosed with endometriosis initially present to their gynecologist with dyspareunia.”11
“Episodic pain with menses may become more constant, lasting for many days of the month,” says Dr. Stratton. “Women with dyschezia or dysuria may have endometriosis lesions associated with the bowel or bladder, respectively.12 When women with these symptoms do not have lesions on bowel or bladder, these pain symptoms may occur because of higher peritoneal hormone and inflammatory factor levels or because adjacent organs share the neural networks.”
Dr. Giudice views the history similarly.
“I believe listening to the patient is essential in evaluating the possibility of her having endometriosis. This involves asking her to describe where her pain is, grading it on a scale of 1 to 10, identifying when in her cycle it occurs, and learning what makes it better or worse,” she says.
“It also is important to assess the quality of the pain,” Dr. Giudice says. “Does it radiate, does it limit her daily activities, does it interfere with her relationships, intercourse, work, school? Is it associated with bowel movements, urination, other pain syndromes?”
“Having a pain questionnaire is a great help so that patients have a chance to reflect on these and other questions that help to frame the pain associated with endometriosis when they come for consultation,” she adds.
By determining if pain is associated with menstruation or spotting, the clinician is better informed about the value of menstrual suppression, says Dr. Stratton. “Determining what makes the pain better or worse can help define triggers which, if treated, can decrease the likelihood of episodes of pain.”
“A detailed history of any medical or surgical treatments and their outcome is helpful in guiding future treatment,” she adds. “While hormonal therapy has been a mainstay of treatment, in some women, some hormonal treatments may worsen pain or have unacceptable side effects like worsening depression or anxiety. In addition, some pain—especially that associated with deep lesions—may be relieved by surgical treatment13,14; pain that worsened after surgery may suggest neural damage.”
“As there is an engagement of the central nervous system, endometriosis is considered a central sensitivity syndrome in which women may also have other sites of pain,” Dr. Stratton says. “Thus, obtaining a history about current symptoms or prior diagnosis of irritable bowel syndrome, interstitial cystitis/painful bladder, migraines, fibromyalgia, or chronic fatigue syndrome is beneficial.10,15–17 Facilitating treatment for these comorbidities is a key principle in helping women with endometriosis-associated pain, as any condition that triggers or perpetuates pain warrants treatment.”
4. What should the physical exam entail?
“An abdominal exam and a pelvic exam are essential in evaluating pain in a woman when endometriosis is suspected,” says Dr. Giudice. “Sometimes the latter is challenging in young teens and can be deferred.” Overall, however, “the pelvic exam can give insight into pain triggers, adnexal masses (possible endometriomas) and mobility of pelvic organs. A rectovaginal exam is important in evaluating deep infiltrating disease and to gauge the pelvic pain landscape overall. In addition, palpating the pelvic floor musculature is important to distinguish pelvic floor muscle spasm from endometriosis pain.”
“The challenge for clinicians is to think beyond the endometrial implants, taking into account multiple factors that influence pain perception,” says Dr. Stratton. During the examination, the clinician should begin by mapping the regions of pain in the abdomen and back, “distinguishing musculoskeletal pain from deep pain. Determining whether pains are focused or diffuse is also important.”
Dr. Stratton recommends that the routine pelvic exam be modified because a standard bimanual exam “confuses pain signals from the pelvic floor, abdominal wall, bladder, and other viscera. For this reason, a pain-oriented assessment is mandatory.”
Begin with a single digital examination to map tender areas, Dr. Stratton advises. Then consider the size, shape, and mobility of reproductive and pelvic organs. “A bimanual exam will help identify adnexal masses like endometriomas,” she says.
Endometriomas usually are not associated with pain, she adds, but “they are associated with deep infiltrating lesions. Nodularity along the uterosacral ligaments, limited reproductive organ mobility, and thickening of the rectovaginal septum also suggest deep infiltrating lesions. Importantly, deep infiltrating lesions are the lesion type most associated with pain.”18,19
5. Is imaging useful in the diagnosis of endometriosis?
Laparoscopy remains the gold standard for diagnosis of endometriosis, observes Steven R. Goldstein, MD. Visualization of endometriotic implants at the time of surgery—with histologic assessment—offers definitive confirmation of the diagnosis. The physical examination, too, can offer a strong suggestion of endometriosis, he says. Dr. Goldstein is professor of obstetrics and gynecology at New York University School of Medicine and director of gynecologic ultrasound and co-director of bone densitometry at New York University Medical Center in New York City. He serves on the OBG Management Board of Editors.
“In the past, the pelvic examination and history often were the sine qua non for patients with pain,” Dr. Goldstein says. “Extreme dysmenorrhea and pain between periods, especially with intercourse, defecation, and exercise, all increased the suspicion of endometriosis. People used to talk about feeling nodularity in the uterosacral ligaments and finding decreased mobility of pelvic structures—but I don’t have any question that the skill of today’s gynecologists in doing a bimanual pelvic exam is a fraction of what it was in years gone by because they haven’t had the necessity of experience. The first thing they do if there’s any question is they send the patient for an ultrasound.”
Of course, ultrasound can be especially helpful in identifying endometriomas—sometimes called “chocolate cysts”—in the ovary. Endometriomas can have a solid appearance on ultrasound, says Dr. Goldstein, because the fluid they contain (dried blood) is sonolucent or pure black on ultrasound, similar to amniotic fluid or the fluid seen in the bladder. “This ‘chocolate’ fluid contained in endometriomas is homogeneous, particulate, and very monotonous in its appearance, in contrast to the internal echoes observed in hemorrhagic corpus lutea, which are very cobweblike and can sometimes mimic papillary projections,” he adds.
“What’s absolutely essential when imaging a suspected endometrioma by ultrasound is that there be no evidence of any blood flow contained within that structure. Because it’s dried blood, it shouldn’t have any vascularity. If you see blood flow inside what you would call an endometrioma, you need to rethink your diagnosis,” he says.
In some cases, a supposed endometriomalacks a black, sonolucent appearance, but “the clinician often can tell that it’s a cystic structure by the very bright posterior wall—what we call posterior wall acoustic enhancement—even though the interior of the structure may appear sort of grayish or whitish rather than the pure black of a simple cyst. It’s still fluid-filled,” Dr. Goldstein says.
In some instances, even endometriotic nodules can be imaged by ultrasound, he adds. “There’s an increasing body of literature that suggests that, if you look carefully in people with deep infiltrating endometriosis, you can often see solid-appearing nodules in the rectovaginal septum or between the uterus and bladder. With the kind of resolution that we now have with the vaginal probe, some of these nodules can be seen. That’s somewhat new, and it’s a function of 2 things—people looking for endometriosis and the better resolution of more modern equipment.”
Dr. Goldstein believes that magnetic resonance imaging (MRI) is “almost never” indicated in the diagnosis of endometriosis. A more helpful approach would be a consultative ultrasound with someone with more experience. However, when that is not available, or “in areas where you have excellent backup in terms of pelvic MRI, that may be the way to go. I don’t think so,” he demurs, “and some of my colleagues would be very upset at the thought of needing to use MRI to diagnose endometriosis. But in the occasional confusing or difficult case, depending on the quality of the referral pattern you have, it might make sense,” he says.
6. When is diagnostic laparoscopy clearly indicated?
Dr. Giudice believes that laparoscopy—with the intention to treat endometriosis, if present—“is essential when first-line medical therapy fails or when pain is acute and severe.”5
Dr. Stratton concurs. “Any woman with chronic pain wants to know what is causing the pain,” she says. Therefore, “women report a benefit from knowing that their pain is associated with endometriosis.6 However, diagnostic laparoscopy alone, with the sole purpose of determining the presence of endometriosis but not treating the lesions, is no longer performed, as it poses little benefit to the patient other than peace of mind.”
“The general trend in the United States has been to first use hormonal treatments when the diagnosis of endometriosis is suspected, prior to performing surgery,” Dr. Stratton says.1 In many cases, by using cyclic combined hormonal contraceptives to reduce menstrual flow or “suppressing menstruation with continuous combined hormonal contraceptives,” gonadotropin-releasing hormone analogues (combined with progestin to prevent bone loss), “or continuous progestin alone may be effective in decreasing pain. Not surprisingly, these hormonal approaches are effective for any chronic pelvic pain, even for women who do not have the surgical diagnosis of endometriosis.”20
“When the first-line approach to chronic pelvic pain is hormonal treatment, laparoscopy is considered when these medical treatments have failed to control the pain or are poorly tolerated, or when the diagnosis of endometriosis is in question,” Dr. Stratton says.
“Laparoscopy to treat endometriomas is indicated if an endometrioma is enlarging, measures more than 4 cm in diameter, or if the diagnosis of an ovarian mass is in question,” she explains. “While surgeons have previously been aggressive in removing endometriomas, this practice may have negative consequences on ovarian function. Because endometriomas are pseudocysts, removing them completely leads to the removal of viable ovarian tissue and may diminish ovarian reserve.”21,22
7. What is the surgical appearance of endometriosis?
Dr. Giudice returns to the enigmatic nature of endometriosis in addressing this question, mentioning its “many faces” at the time of surgery. “It is imperative that the surgeon recognize the disease in its many forms,” she says. “Also, it is especially helpful at the time of surgery if suspected lesions are biopsied and sent to pathology to have the diagnosis made unequivocally.”5
As for the surgical appearance of endometriosis, Dr. Stratton notes that there are 3 types of lesions—“superficial lesions, deep infiltrating lesions, and endometriomas. Endometriomas occur almost exclusively in the ovary and are pseudocysts without an identifiable cystic lining. They vary in dimension from a few millimeters to several centimeters.”
“Superficial peritoneal endometriosis lesions have a variable appearance, with some lesions being clear or red, some brown, blue or black, and some having a white appearance, like a scar,” says Dr. Stratton. “Endometriosis can be diagnosed on histologic examination of any of these lesion types.
“Overall, single-color lesions have similar frequencies of biopsy-confirmed endometriosis (59% to 62%),” she says.23 “These lesion appearances likely represent different stages of development of endometriosis, with red or clear lesions occurring first, soon after endometrial tissue implantation; black, blue, or brown lesions occurring later, in response to the hormones varying in the menstrual cycle; and white lesions occurring as the lesions age. Deep infiltrating lesions generally have blue/black or white features.”
“Wide, deep, multiple-color lesions in the cul-de-sac, ovarian fossa or uterosacral ligaments are most likely endometriosis,” Dr. Stratton adds.23 Only lesions with multiple colors have a significantly higher percentage of positive biopsies (76%). Importantly, over half of women with only subtle lesions (small red or white lesions) have endometriosis.
CASE Resolved
You tell the patient that endometriosis is one of the possible diagnoses for her chronic pelvic pain, and you take a focused history. During a pelvic examination, you observe that her right ovary lacks mobility, and you map a number of trigger points for her pain. Transvaginal ultrasound results suggest the presence of nodules in the rectovaginal septum. You begin empiric treatment with continuous combined hormonal contraceptives to suppress menstruation. On her next visit, the patient reports reduced but still bothersome pain. Laparoscopy reveals a 2-cm endometrioma in the right ovary and deep infiltrating lesions in the cul-de-sac. The endometrioma is resected. Histology confirms the diagnosis of endometriosis.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. American College of Obstetricians and Gynecologists. Practice Bulletin #114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–236.
2. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA. Endometriosis in association with uterine anomaly. Am J Obstet Gynecol. 1986;154(1):39–43.
3. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
4. Berkley KJ, Stratton P. Mechanisms: lessons from translational studies of endometriosis. In: Giamberardino MA, ed. Visceral Pain: Clinical, Pathophysiological and Therapeutic Aspects. Oxford, UK: Oxford University Press; 2009:39–50.
5. Giudice LC. Clinical practice: endometriosis. N Engl J Med. 2010;362(25):2389–2398.
6. Ballard K, Lowton K, Wright J. What’s the delay: a qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.
7. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.
8. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637–653.
9. Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155(12):4986–4999.
10. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715–2724.
11. De Graaff AA, D’Hooghe TM, Dunselman GA, et al. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677–2685.
12. Lafay Pillet MC, Huchon C, Santulli P, Borghese B, Chapron C, Fauconnier A. A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod. 2014;29(8):1666–1676.
13. Healey M, Cheng C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol. 2014;21(6):999–1004.
14. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis G, Noel JC. Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Invest. 2011;71(2):112–117.
15. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.
16. Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril. 2011;95(3):895–899.
17. Berkley KJ. A life of pelvic pain. Physiol Behav. 2005;86(3):272–280.
18. Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005;11(6):595–606.
19. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266–271.
20. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol. 1999;93(1):51–58.
21. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29(10):2190–2198.
22. Muzii L, Luciano AA, Zupi E, Panici PB. Effect of surgery for endometrioma on ovarian function: a different point of view. J Minim Invasive Gynecol. 2014;21(4):531–533.
23. Stegmann BJ, Sinaii N, Liu S, et al. Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women. Fertil Steril. 2008;89(6):1632–1636.
CASE Is her chronic pelvic pain caused by endometriosis?
M.L. is a 32-year-old nulliparous woman who is referred to your office by her primary care provider for chronic pelvic pain. She reports severe dysmenorrhea as her main symptom, but she also mentions dyspareunia. She says these symptoms have been present for several years but have increased in intensity gradually. She asks what you consider to be the most likely diagnosis.
What potential diagnoses do you mention to her? And how do you identify the cause of her pain?
Although endometriosis—the presence of endometrial tissue outside the uterus—affects at least 5 million women of reproductive age in the United States alone, it can be a challenging diagnosis for several reasons.
“Endometriosis is a great masquerader,” says Linda Giudice, MD, PhD. “It presents with a variety of pain patterns, intensities, and triggers. It can also involve symptoms that overlap those of other disorders, including disorders of the gastrointestinal and urinary tracts.”
Although endometriosis falls within the differential diagnosis of chronic pelvic pain, “it is usually not high on the list in the primary care setting (adult and adolescent),” Dr. Giudice adds. She is the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
John R. Lue, MD, MPH, an author of the most recent practice bulletin on endometriosis from the American College of Obstetricians and Gynecologists,1 sees the situation similarly.
“The main challenge in the diagnosis of endometriosis is that its presentation mimics other causes of chronic pelvic pain,” he says. “Pelvic pain due to endometriosis is usually chronic (lasting ≥6 months). It is associated with dysmenorrhea in 50% to 90% of cases, as well as with dyspareunia, deep pelvic pain, and lower abdominal pain with or without back and loin pain. The pain can occur unpredictably and intermittently throughout the menstrual cycle or it can be continuous. In addition, it can be dull, throbbing, or sharp and may be exacerbated by physical activity.2,3 Up to 20% of women with endometriosis have concurrent pain conditions.”4 Dr. Lue is associate professor, chief of the section of general obstetrics and gynecology, and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
Among other diseases of the female pelvis that have relatively similar presentation, Dr. Lue adds, are pathologies of the:
- uterus (adenomyosis, fibroids)
- fallopian tube (hydrosalpinx)
- ovaries (ovarian cysts)
- bladder (interstitial cystitis)
- bowel (irritable bowel syndrome)
- musculoskeletal system (piriformis syndrome).
Before pelvic pain is attributed to endometriosis, he says, the provider should rule out bowel, bladder, musculoskeletal, and psychiatric causes.
This article focuses on 7 questions, the answers of which are critical to narrowing in on the diagnosis of endometriosis, including essential factors to consider in the patient history, imaging and other diagnostic tools, and considerations in surgical exploration. In the second and third installments of this in-depth series on endometriosis, pain and infertility will be the respective subjects of investigation.
Several theories explain the “why” of endometriosis
A dominant theory is that peritoneal endometrial implants arise from retrograde menstruation, during which endometrial tissue passes through the fallopian tubes into the pelvis, says John R. Lue, MD, MPH. Dr. Lue is associate professor and chief of the section of general obstetrics and gynecology and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
“Additional theories include immune dysfunction that interferes with clearing of endometrial lesions in the pelvis, as well as genetic alterations that lead to growth dysregulation,” he says.1 “These theories all have merit, and it is likely that the pathogenesis of endometriosis is multifactorial.”
Another strong theory involves the homeobox (HOX) genes, “which mediate embryonic development,” says Dr. Lue.2,3 “These genes are translated into transcription factors that regulate downstream genes necessary for growth and differentiation. It has been demonstrated that HOX genes play an analogous role in endometrial development during the adult menstrual cycle.4 HOX gene expression regulates the growth and development of the human endometrium.5 The expression of HOX genes A10 and A11 varies in response to sex steroids during the menstrual cycle, with dramatic upregulation in the mid-secretory phase,” says Dr. Lue. Recent studies suggest that these genes “play a major role” in endometriosis.6
“Since ovarian endometriomas are clonal and lesions usually have genetic mutations, such somatic mutations with subsequent growth dysregulation may also be etiologic factors,” says Dr. Lue.1,7,8 “Disease at distant sites may be caused by lymphatic or hematogenous spread or metaplastic transformation.”
References
1. Giudice LC, Swierz LM, Burney RO. Edometriosis. In: Jameson JL, DeGroot LJ, eds. Endocrinology. 6th ed. New York, NY: Elsevier; 2010:2356–2370.
2. Krumlauf R. Hox genes in vertebrate development. Cell. 1992;78(2):191–201.
3. McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283–302.
4. Taylor H, Igarashi P, Olive D, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999;84(3):1129–1135.
5. Taylor H, Vanden Heuvel GB, Igarashi P. A conserved HOX axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the HOXA cluster genes. Biol Reprod. 1997;57(6):1338–1345.
6. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
7. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269.
8. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
1. Why such a long delay in diagnosis?
Investigators exploring the length of time between a patient’s presentation with symptoms and diagnosis have found it to be particularly long for endometriosis, ranging from 6 to 11 years.
Because endometriosis is usually not high on the list of differential diagnoses for chronic pelvic pain in the primary care setting, a patient may not be referred to a gynecologist unless those symptoms include severe dysmenorrhea, dyspareunia, or similar findings. Once the referral is made, the gynecologist “will usually try contraceptive steroids, nonsteroidal anti-inflammatory drugs, or second-line progestins before a diagnosis is made,” says Dr. Giudice.5
The delay in diagnosis “is astounding,” she adds, “and has its roots in empiric medical therapies and a combination of patients fearing a diagnosis of cancer and reluctance of gynecologists to perform laparoscopy on adolescents.”6
Another possible cause of diagnostic delay: Some adolescent girls may not realize when their pain is severe. Because they may have always experienced a high degree of pain since menarche, they may assume it to be a normal aspect of womanhood and delay seeking help, says Pamela Stratton, MD, chief of the gynecology consult service at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
2. Have any biomarkers proved to be useful diagnostic tools?
Any biomarker proven to reliably identify endometriosis would be a boon to medicine, as it would provide a noninvasive or minimally invasive alternative to diagnostic laparoscopy, the current gold standard. Regrettably, the search for such a biomarker has produced “disappointing results,” says Dr. Giudice.
“Recent systematic reviews of all proposed endometriosis-related biomarkers over the last 25 years in serum, plasma, urine, and endometrium could not identify an unequivocally clinically useful biomarker or panel of biomarkers,” she notes.7,8 “This is due mainly to low numbers of subjects, small populations for validations, cycle/hormonal- and disease stage-dependence, poorly defined controls, and low sensitivity and specificity.”
One hopeful development: “Whole genome transcriptomics of archived endometrial tissue and machine learning found several classifiers to diagnose and stage endometriosis with high accuracy that were validated on an independent sample set,” says Dr. Giudice.9 “However, these data now warrant a prospective, multisite study for further validation.”
Environmental factors, estrogen, and endometriosis
“There is increasing evidence that in utero and also adult exposures to endocrine-disrupting chemicals (EDCs) play a role in the pathogenesis and progression of disease,” says Linda Giudice, MD, PhD, the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
“For example, the Nurses’ Health Study II, a prospective cohort study of more than 80,000 women, revealed that daughters exposed to diethylstilbestrol (DES) had an 80% increased risk (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.8) of developing endometriosis,” she says.1
“Also, dioxin (TCDD) exposure in rats in utero on gestational day 8 increased the size of endometriosis lesions when combined with an adult exposure,” Dr. Giudice says.2 Although we do not know the precise mechanisms underlying in utero events that result in disease onset as a teen or adult, abnormal programming of the female reproductive tract by EDCs and similar agents is believed to play a role, she says.3
Because estrogen is essential for endometriosis lesions and associated symptoms to progress, “EDCs that have either estrogenic activity or interfere with estrogen metabolism or action, or both, have been proposed as contributors to progression of disease. Abundant animal data using nonhuman primate and rodent models and exposures to organochlorines and other EDCs support this hypothesis,” Dr. Giudice says.4
“The weight of human evidence of associations of EDCs and the risk of endometriosis in adult women depends on the class of endocrine disrupter,” Dr. Giudice continues. “Strongest correlations are with polychlorobiphenyls (PCBs), where 10 of 12 studies found significant odds of disease and circulating or omental fat concentrations of these compounds. PCBs inhibit peripheral natural killer cell activity and interleukin 1b and 12 production, relevant to the immune component of endometriosis progression.”
“Significant risk has also been associated with organochlorines (in three of three studies) and perfluorochemicals. In contrast, data linking endometriosis with exposures to dioxins, phthalates, and bisphenol A are equivocal, with some studies finding significant odds ratios and others failing to find significant correlations. Interestingly, dioxins have a significant association with deep infiltrating endometriotic lesions.”5
References
1. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Michels KB, Hunter DJ. In utero exposures and the incidence of endometriosis. Fertil Steril. 2004;82(6):1501–1508.
2. Cummings AM, Hedge JM, Birnbaum LS. Effects on prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice. Toxicol Sci. 1999;52(1):45–49.
3. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
4. Crain DA, Janssen SJ, Edwards TM, et al. Female reproductive disorders: the roles of endocrine disrupting compounds and developmental timing. Fertil Steril. 2008;90(4):911–940.
5. Heilier JF, Donnez J, Nackers F, et al. Environmental and host-associated risk factors in endometriosis and deep endometriotic nodules: a matched case-control study. Environ Res. 2007;103(1):121–129.
3. What aspects of the patient history are key?
Dr. Stratton recommends that clinicians begin their evaluation of the patient with pain by asking her to describe that pain—how long she has had it, when it occurs, and which areas are affected.
“Most women with endometriosis-associated pain have chronic pelvic pain,” Dr. Stratton continues.5 “Up to 90% of those have dysmenorrhea or cyclic pain with menses.”10 In addition, women with endometriosis “commonly report having pain with any bleeding or spotting. About 30% of women diagnosed with endometriosis initially present to their gynecologist with dyspareunia.”11
“Episodic pain with menses may become more constant, lasting for many days of the month,” says Dr. Stratton. “Women with dyschezia or dysuria may have endometriosis lesions associated with the bowel or bladder, respectively.12 When women with these symptoms do not have lesions on bowel or bladder, these pain symptoms may occur because of higher peritoneal hormone and inflammatory factor levels or because adjacent organs share the neural networks.”
Dr. Giudice views the history similarly.
“I believe listening to the patient is essential in evaluating the possibility of her having endometriosis. This involves asking her to describe where her pain is, grading it on a scale of 1 to 10, identifying when in her cycle it occurs, and learning what makes it better or worse,” she says.
“It also is important to assess the quality of the pain,” Dr. Giudice says. “Does it radiate, does it limit her daily activities, does it interfere with her relationships, intercourse, work, school? Is it associated with bowel movements, urination, other pain syndromes?”
“Having a pain questionnaire is a great help so that patients have a chance to reflect on these and other questions that help to frame the pain associated with endometriosis when they come for consultation,” she adds.
By determining if pain is associated with menstruation or spotting, the clinician is better informed about the value of menstrual suppression, says Dr. Stratton. “Determining what makes the pain better or worse can help define triggers which, if treated, can decrease the likelihood of episodes of pain.”
“A detailed history of any medical or surgical treatments and their outcome is helpful in guiding future treatment,” she adds. “While hormonal therapy has been a mainstay of treatment, in some women, some hormonal treatments may worsen pain or have unacceptable side effects like worsening depression or anxiety. In addition, some pain—especially that associated with deep lesions—may be relieved by surgical treatment13,14; pain that worsened after surgery may suggest neural damage.”
“As there is an engagement of the central nervous system, endometriosis is considered a central sensitivity syndrome in which women may also have other sites of pain,” Dr. Stratton says. “Thus, obtaining a history about current symptoms or prior diagnosis of irritable bowel syndrome, interstitial cystitis/painful bladder, migraines, fibromyalgia, or chronic fatigue syndrome is beneficial.10,15–17 Facilitating treatment for these comorbidities is a key principle in helping women with endometriosis-associated pain, as any condition that triggers or perpetuates pain warrants treatment.”
4. What should the physical exam entail?
“An abdominal exam and a pelvic exam are essential in evaluating pain in a woman when endometriosis is suspected,” says Dr. Giudice. “Sometimes the latter is challenging in young teens and can be deferred.” Overall, however, “the pelvic exam can give insight into pain triggers, adnexal masses (possible endometriomas) and mobility of pelvic organs. A rectovaginal exam is important in evaluating deep infiltrating disease and to gauge the pelvic pain landscape overall. In addition, palpating the pelvic floor musculature is important to distinguish pelvic floor muscle spasm from endometriosis pain.”
“The challenge for clinicians is to think beyond the endometrial implants, taking into account multiple factors that influence pain perception,” says Dr. Stratton. During the examination, the clinician should begin by mapping the regions of pain in the abdomen and back, “distinguishing musculoskeletal pain from deep pain. Determining whether pains are focused or diffuse is also important.”
Dr. Stratton recommends that the routine pelvic exam be modified because a standard bimanual exam “confuses pain signals from the pelvic floor, abdominal wall, bladder, and other viscera. For this reason, a pain-oriented assessment is mandatory.”
Begin with a single digital examination to map tender areas, Dr. Stratton advises. Then consider the size, shape, and mobility of reproductive and pelvic organs. “A bimanual exam will help identify adnexal masses like endometriomas,” she says.
Endometriomas usually are not associated with pain, she adds, but “they are associated with deep infiltrating lesions. Nodularity along the uterosacral ligaments, limited reproductive organ mobility, and thickening of the rectovaginal septum also suggest deep infiltrating lesions. Importantly, deep infiltrating lesions are the lesion type most associated with pain.”18,19
5. Is imaging useful in the diagnosis of endometriosis?
Laparoscopy remains the gold standard for diagnosis of endometriosis, observes Steven R. Goldstein, MD. Visualization of endometriotic implants at the time of surgery—with histologic assessment—offers definitive confirmation of the diagnosis. The physical examination, too, can offer a strong suggestion of endometriosis, he says. Dr. Goldstein is professor of obstetrics and gynecology at New York University School of Medicine and director of gynecologic ultrasound and co-director of bone densitometry at New York University Medical Center in New York City. He serves on the OBG Management Board of Editors.
“In the past, the pelvic examination and history often were the sine qua non for patients with pain,” Dr. Goldstein says. “Extreme dysmenorrhea and pain between periods, especially with intercourse, defecation, and exercise, all increased the suspicion of endometriosis. People used to talk about feeling nodularity in the uterosacral ligaments and finding decreased mobility of pelvic structures—but I don’t have any question that the skill of today’s gynecologists in doing a bimanual pelvic exam is a fraction of what it was in years gone by because they haven’t had the necessity of experience. The first thing they do if there’s any question is they send the patient for an ultrasound.”
Of course, ultrasound can be especially helpful in identifying endometriomas—sometimes called “chocolate cysts”—in the ovary. Endometriomas can have a solid appearance on ultrasound, says Dr. Goldstein, because the fluid they contain (dried blood) is sonolucent or pure black on ultrasound, similar to amniotic fluid or the fluid seen in the bladder. “This ‘chocolate’ fluid contained in endometriomas is homogeneous, particulate, and very monotonous in its appearance, in contrast to the internal echoes observed in hemorrhagic corpus lutea, which are very cobweblike and can sometimes mimic papillary projections,” he adds.
“What’s absolutely essential when imaging a suspected endometrioma by ultrasound is that there be no evidence of any blood flow contained within that structure. Because it’s dried blood, it shouldn’t have any vascularity. If you see blood flow inside what you would call an endometrioma, you need to rethink your diagnosis,” he says.
In some cases, a supposed endometriomalacks a black, sonolucent appearance, but “the clinician often can tell that it’s a cystic structure by the very bright posterior wall—what we call posterior wall acoustic enhancement—even though the interior of the structure may appear sort of grayish or whitish rather than the pure black of a simple cyst. It’s still fluid-filled,” Dr. Goldstein says.
In some instances, even endometriotic nodules can be imaged by ultrasound, he adds. “There’s an increasing body of literature that suggests that, if you look carefully in people with deep infiltrating endometriosis, you can often see solid-appearing nodules in the rectovaginal septum or between the uterus and bladder. With the kind of resolution that we now have with the vaginal probe, some of these nodules can be seen. That’s somewhat new, and it’s a function of 2 things—people looking for endometriosis and the better resolution of more modern equipment.”
Dr. Goldstein believes that magnetic resonance imaging (MRI) is “almost never” indicated in the diagnosis of endometriosis. A more helpful approach would be a consultative ultrasound with someone with more experience. However, when that is not available, or “in areas where you have excellent backup in terms of pelvic MRI, that may be the way to go. I don’t think so,” he demurs, “and some of my colleagues would be very upset at the thought of needing to use MRI to diagnose endometriosis. But in the occasional confusing or difficult case, depending on the quality of the referral pattern you have, it might make sense,” he says.
6. When is diagnostic laparoscopy clearly indicated?
Dr. Giudice believes that laparoscopy—with the intention to treat endometriosis, if present—“is essential when first-line medical therapy fails or when pain is acute and severe.”5
Dr. Stratton concurs. “Any woman with chronic pain wants to know what is causing the pain,” she says. Therefore, “women report a benefit from knowing that their pain is associated with endometriosis.6 However, diagnostic laparoscopy alone, with the sole purpose of determining the presence of endometriosis but not treating the lesions, is no longer performed, as it poses little benefit to the patient other than peace of mind.”
“The general trend in the United States has been to first use hormonal treatments when the diagnosis of endometriosis is suspected, prior to performing surgery,” Dr. Stratton says.1 In many cases, by using cyclic combined hormonal contraceptives to reduce menstrual flow or “suppressing menstruation with continuous combined hormonal contraceptives,” gonadotropin-releasing hormone analogues (combined with progestin to prevent bone loss), “or continuous progestin alone may be effective in decreasing pain. Not surprisingly, these hormonal approaches are effective for any chronic pelvic pain, even for women who do not have the surgical diagnosis of endometriosis.”20
“When the first-line approach to chronic pelvic pain is hormonal treatment, laparoscopy is considered when these medical treatments have failed to control the pain or are poorly tolerated, or when the diagnosis of endometriosis is in question,” Dr. Stratton says.
“Laparoscopy to treat endometriomas is indicated if an endometrioma is enlarging, measures more than 4 cm in diameter, or if the diagnosis of an ovarian mass is in question,” she explains. “While surgeons have previously been aggressive in removing endometriomas, this practice may have negative consequences on ovarian function. Because endometriomas are pseudocysts, removing them completely leads to the removal of viable ovarian tissue and may diminish ovarian reserve.”21,22
7. What is the surgical appearance of endometriosis?
Dr. Giudice returns to the enigmatic nature of endometriosis in addressing this question, mentioning its “many faces” at the time of surgery. “It is imperative that the surgeon recognize the disease in its many forms,” she says. “Also, it is especially helpful at the time of surgery if suspected lesions are biopsied and sent to pathology to have the diagnosis made unequivocally.”5
As for the surgical appearance of endometriosis, Dr. Stratton notes that there are 3 types of lesions—“superficial lesions, deep infiltrating lesions, and endometriomas. Endometriomas occur almost exclusively in the ovary and are pseudocysts without an identifiable cystic lining. They vary in dimension from a few millimeters to several centimeters.”
“Superficial peritoneal endometriosis lesions have a variable appearance, with some lesions being clear or red, some brown, blue or black, and some having a white appearance, like a scar,” says Dr. Stratton. “Endometriosis can be diagnosed on histologic examination of any of these lesion types.
“Overall, single-color lesions have similar frequencies of biopsy-confirmed endometriosis (59% to 62%),” she says.23 “These lesion appearances likely represent different stages of development of endometriosis, with red or clear lesions occurring first, soon after endometrial tissue implantation; black, blue, or brown lesions occurring later, in response to the hormones varying in the menstrual cycle; and white lesions occurring as the lesions age. Deep infiltrating lesions generally have blue/black or white features.”
“Wide, deep, multiple-color lesions in the cul-de-sac, ovarian fossa or uterosacral ligaments are most likely endometriosis,” Dr. Stratton adds.23 Only lesions with multiple colors have a significantly higher percentage of positive biopsies (76%). Importantly, over half of women with only subtle lesions (small red or white lesions) have endometriosis.
CASE Resolved
You tell the patient that endometriosis is one of the possible diagnoses for her chronic pelvic pain, and you take a focused history. During a pelvic examination, you observe that her right ovary lacks mobility, and you map a number of trigger points for her pain. Transvaginal ultrasound results suggest the presence of nodules in the rectovaginal septum. You begin empiric treatment with continuous combined hormonal contraceptives to suppress menstruation. On her next visit, the patient reports reduced but still bothersome pain. Laparoscopy reveals a 2-cm endometrioma in the right ovary and deep infiltrating lesions in the cul-de-sac. The endometrioma is resected. Histology confirms the diagnosis of endometriosis.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
CASE Is her chronic pelvic pain caused by endometriosis?
M.L. is a 32-year-old nulliparous woman who is referred to your office by her primary care provider for chronic pelvic pain. She reports severe dysmenorrhea as her main symptom, but she also mentions dyspareunia. She says these symptoms have been present for several years but have increased in intensity gradually. She asks what you consider to be the most likely diagnosis.
What potential diagnoses do you mention to her? And how do you identify the cause of her pain?
Although endometriosis—the presence of endometrial tissue outside the uterus—affects at least 5 million women of reproductive age in the United States alone, it can be a challenging diagnosis for several reasons.
“Endometriosis is a great masquerader,” says Linda Giudice, MD, PhD. “It presents with a variety of pain patterns, intensities, and triggers. It can also involve symptoms that overlap those of other disorders, including disorders of the gastrointestinal and urinary tracts.”
Although endometriosis falls within the differential diagnosis of chronic pelvic pain, “it is usually not high on the list in the primary care setting (adult and adolescent),” Dr. Giudice adds. She is the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
John R. Lue, MD, MPH, an author of the most recent practice bulletin on endometriosis from the American College of Obstetricians and Gynecologists,1 sees the situation similarly.
“The main challenge in the diagnosis of endometriosis is that its presentation mimics other causes of chronic pelvic pain,” he says. “Pelvic pain due to endometriosis is usually chronic (lasting ≥6 months). It is associated with dysmenorrhea in 50% to 90% of cases, as well as with dyspareunia, deep pelvic pain, and lower abdominal pain with or without back and loin pain. The pain can occur unpredictably and intermittently throughout the menstrual cycle or it can be continuous. In addition, it can be dull, throbbing, or sharp and may be exacerbated by physical activity.2,3 Up to 20% of women with endometriosis have concurrent pain conditions.”4 Dr. Lue is associate professor, chief of the section of general obstetrics and gynecology, and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
Among other diseases of the female pelvis that have relatively similar presentation, Dr. Lue adds, are pathologies of the:
- uterus (adenomyosis, fibroids)
- fallopian tube (hydrosalpinx)
- ovaries (ovarian cysts)
- bladder (interstitial cystitis)
- bowel (irritable bowel syndrome)
- musculoskeletal system (piriformis syndrome).
Before pelvic pain is attributed to endometriosis, he says, the provider should rule out bowel, bladder, musculoskeletal, and psychiatric causes.
This article focuses on 7 questions, the answers of which are critical to narrowing in on the diagnosis of endometriosis, including essential factors to consider in the patient history, imaging and other diagnostic tools, and considerations in surgical exploration. In the second and third installments of this in-depth series on endometriosis, pain and infertility will be the respective subjects of investigation.
Several theories explain the “why” of endometriosis
A dominant theory is that peritoneal endometrial implants arise from retrograde menstruation, during which endometrial tissue passes through the fallopian tubes into the pelvis, says John R. Lue, MD, MPH. Dr. Lue is associate professor and chief of the section of general obstetrics and gynecology and medical director of women’s ambulatory services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.
“Additional theories include immune dysfunction that interferes with clearing of endometrial lesions in the pelvis, as well as genetic alterations that lead to growth dysregulation,” he says.1 “These theories all have merit, and it is likely that the pathogenesis of endometriosis is multifactorial.”
Another strong theory involves the homeobox (HOX) genes, “which mediate embryonic development,” says Dr. Lue.2,3 “These genes are translated into transcription factors that regulate downstream genes necessary for growth and differentiation. It has been demonstrated that HOX genes play an analogous role in endometrial development during the adult menstrual cycle.4 HOX gene expression regulates the growth and development of the human endometrium.5 The expression of HOX genes A10 and A11 varies in response to sex steroids during the menstrual cycle, with dramatic upregulation in the mid-secretory phase,” says Dr. Lue. Recent studies suggest that these genes “play a major role” in endometriosis.6
“Since ovarian endometriomas are clonal and lesions usually have genetic mutations, such somatic mutations with subsequent growth dysregulation may also be etiologic factors,” says Dr. Lue.1,7,8 “Disease at distant sites may be caused by lymphatic or hematogenous spread or metaplastic transformation.”
References
1. Giudice LC, Swierz LM, Burney RO. Edometriosis. In: Jameson JL, DeGroot LJ, eds. Endocrinology. 6th ed. New York, NY: Elsevier; 2010:2356–2370.
2. Krumlauf R. Hox genes in vertebrate development. Cell. 1992;78(2):191–201.
3. McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283–302.
4. Taylor H, Igarashi P, Olive D, Arici A. Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999;84(3):1129–1135.
5. Taylor H, Vanden Heuvel GB, Igarashi P. A conserved HOX axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the HOXA cluster genes. Biol Reprod. 1997;57(6):1338–1345.
6. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
7. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269.
8. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
1. Why such a long delay in diagnosis?
Investigators exploring the length of time between a patient’s presentation with symptoms and diagnosis have found it to be particularly long for endometriosis, ranging from 6 to 11 years.
Because endometriosis is usually not high on the list of differential diagnoses for chronic pelvic pain in the primary care setting, a patient may not be referred to a gynecologist unless those symptoms include severe dysmenorrhea, dyspareunia, or similar findings. Once the referral is made, the gynecologist “will usually try contraceptive steroids, nonsteroidal anti-inflammatory drugs, or second-line progestins before a diagnosis is made,” says Dr. Giudice.5
The delay in diagnosis “is astounding,” she adds, “and has its roots in empiric medical therapies and a combination of patients fearing a diagnosis of cancer and reluctance of gynecologists to perform laparoscopy on adolescents.”6
Another possible cause of diagnostic delay: Some adolescent girls may not realize when their pain is severe. Because they may have always experienced a high degree of pain since menarche, they may assume it to be a normal aspect of womanhood and delay seeking help, says Pamela Stratton, MD, chief of the gynecology consult service at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
2. Have any biomarkers proved to be useful diagnostic tools?
Any biomarker proven to reliably identify endometriosis would be a boon to medicine, as it would provide a noninvasive or minimally invasive alternative to diagnostic laparoscopy, the current gold standard. Regrettably, the search for such a biomarker has produced “disappointing results,” says Dr. Giudice.
“Recent systematic reviews of all proposed endometriosis-related biomarkers over the last 25 years in serum, plasma, urine, and endometrium could not identify an unequivocally clinically useful biomarker or panel of biomarkers,” she notes.7,8 “This is due mainly to low numbers of subjects, small populations for validations, cycle/hormonal- and disease stage-dependence, poorly defined controls, and low sensitivity and specificity.”
One hopeful development: “Whole genome transcriptomics of archived endometrial tissue and machine learning found several classifiers to diagnose and stage endometriosis with high accuracy that were validated on an independent sample set,” says Dr. Giudice.9 “However, these data now warrant a prospective, multisite study for further validation.”
Environmental factors, estrogen, and endometriosis
“There is increasing evidence that in utero and also adult exposures to endocrine-disrupting chemicals (EDCs) play a role in the pathogenesis and progression of disease,” says Linda Giudice, MD, PhD, the Robert B. Jaffe, MD, Endowed Professor in the reproductive sciences and chair of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.
“For example, the Nurses’ Health Study II, a prospective cohort study of more than 80,000 women, revealed that daughters exposed to diethylstilbestrol (DES) had an 80% increased risk (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2–2.8) of developing endometriosis,” she says.1
“Also, dioxin (TCDD) exposure in rats in utero on gestational day 8 increased the size of endometriosis lesions when combined with an adult exposure,” Dr. Giudice says.2 Although we do not know the precise mechanisms underlying in utero events that result in disease onset as a teen or adult, abnormal programming of the female reproductive tract by EDCs and similar agents is believed to play a role, she says.3
Because estrogen is essential for endometriosis lesions and associated symptoms to progress, “EDCs that have either estrogenic activity or interfere with estrogen metabolism or action, or both, have been proposed as contributors to progression of disease. Abundant animal data using nonhuman primate and rodent models and exposures to organochlorines and other EDCs support this hypothesis,” Dr. Giudice says.4
“The weight of human evidence of associations of EDCs and the risk of endometriosis in adult women depends on the class of endocrine disrupter,” Dr. Giudice continues. “Strongest correlations are with polychlorobiphenyls (PCBs), where 10 of 12 studies found significant odds of disease and circulating or omental fat concentrations of these compounds. PCBs inhibit peripheral natural killer cell activity and interleukin 1b and 12 production, relevant to the immune component of endometriosis progression.”
“Significant risk has also been associated with organochlorines (in three of three studies) and perfluorochemicals. In contrast, data linking endometriosis with exposures to dioxins, phthalates, and bisphenol A are equivocal, with some studies finding significant odds ratios and others failing to find significant correlations. Interestingly, dioxins have a significant association with deep infiltrating endometriotic lesions.”5
References
1. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Michels KB, Hunter DJ. In utero exposures and the incidence of endometriosis. Fertil Steril. 2004;82(6):1501–1508.
2. Cummings AM, Hedge JM, Birnbaum LS. Effects on prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice. Toxicol Sci. 1999;52(1):45–49.
3. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.
4. Crain DA, Janssen SJ, Edwards TM, et al. Female reproductive disorders: the roles of endocrine disrupting compounds and developmental timing. Fertil Steril. 2008;90(4):911–940.
5. Heilier JF, Donnez J, Nackers F, et al. Environmental and host-associated risk factors in endometriosis and deep endometriotic nodules: a matched case-control study. Environ Res. 2007;103(1):121–129.
3. What aspects of the patient history are key?
Dr. Stratton recommends that clinicians begin their evaluation of the patient with pain by asking her to describe that pain—how long she has had it, when it occurs, and which areas are affected.
“Most women with endometriosis-associated pain have chronic pelvic pain,” Dr. Stratton continues.5 “Up to 90% of those have dysmenorrhea or cyclic pain with menses.”10 In addition, women with endometriosis “commonly report having pain with any bleeding or spotting. About 30% of women diagnosed with endometriosis initially present to their gynecologist with dyspareunia.”11
“Episodic pain with menses may become more constant, lasting for many days of the month,” says Dr. Stratton. “Women with dyschezia or dysuria may have endometriosis lesions associated with the bowel or bladder, respectively.12 When women with these symptoms do not have lesions on bowel or bladder, these pain symptoms may occur because of higher peritoneal hormone and inflammatory factor levels or because adjacent organs share the neural networks.”
Dr. Giudice views the history similarly.
“I believe listening to the patient is essential in evaluating the possibility of her having endometriosis. This involves asking her to describe where her pain is, grading it on a scale of 1 to 10, identifying when in her cycle it occurs, and learning what makes it better or worse,” she says.
“It also is important to assess the quality of the pain,” Dr. Giudice says. “Does it radiate, does it limit her daily activities, does it interfere with her relationships, intercourse, work, school? Is it associated with bowel movements, urination, other pain syndromes?”
“Having a pain questionnaire is a great help so that patients have a chance to reflect on these and other questions that help to frame the pain associated with endometriosis when they come for consultation,” she adds.
By determining if pain is associated with menstruation or spotting, the clinician is better informed about the value of menstrual suppression, says Dr. Stratton. “Determining what makes the pain better or worse can help define triggers which, if treated, can decrease the likelihood of episodes of pain.”
“A detailed history of any medical or surgical treatments and their outcome is helpful in guiding future treatment,” she adds. “While hormonal therapy has been a mainstay of treatment, in some women, some hormonal treatments may worsen pain or have unacceptable side effects like worsening depression or anxiety. In addition, some pain—especially that associated with deep lesions—may be relieved by surgical treatment13,14; pain that worsened after surgery may suggest neural damage.”
“As there is an engagement of the central nervous system, endometriosis is considered a central sensitivity syndrome in which women may also have other sites of pain,” Dr. Stratton says. “Thus, obtaining a history about current symptoms or prior diagnosis of irritable bowel syndrome, interstitial cystitis/painful bladder, migraines, fibromyalgia, or chronic fatigue syndrome is beneficial.10,15–17 Facilitating treatment for these comorbidities is a key principle in helping women with endometriosis-associated pain, as any condition that triggers or perpetuates pain warrants treatment.”
4. What should the physical exam entail?
“An abdominal exam and a pelvic exam are essential in evaluating pain in a woman when endometriosis is suspected,” says Dr. Giudice. “Sometimes the latter is challenging in young teens and can be deferred.” Overall, however, “the pelvic exam can give insight into pain triggers, adnexal masses (possible endometriomas) and mobility of pelvic organs. A rectovaginal exam is important in evaluating deep infiltrating disease and to gauge the pelvic pain landscape overall. In addition, palpating the pelvic floor musculature is important to distinguish pelvic floor muscle spasm from endometriosis pain.”
“The challenge for clinicians is to think beyond the endometrial implants, taking into account multiple factors that influence pain perception,” says Dr. Stratton. During the examination, the clinician should begin by mapping the regions of pain in the abdomen and back, “distinguishing musculoskeletal pain from deep pain. Determining whether pains are focused or diffuse is also important.”
Dr. Stratton recommends that the routine pelvic exam be modified because a standard bimanual exam “confuses pain signals from the pelvic floor, abdominal wall, bladder, and other viscera. For this reason, a pain-oriented assessment is mandatory.”
Begin with a single digital examination to map tender areas, Dr. Stratton advises. Then consider the size, shape, and mobility of reproductive and pelvic organs. “A bimanual exam will help identify adnexal masses like endometriomas,” she says.
Endometriomas usually are not associated with pain, she adds, but “they are associated with deep infiltrating lesions. Nodularity along the uterosacral ligaments, limited reproductive organ mobility, and thickening of the rectovaginal septum also suggest deep infiltrating lesions. Importantly, deep infiltrating lesions are the lesion type most associated with pain.”18,19
5. Is imaging useful in the diagnosis of endometriosis?
Laparoscopy remains the gold standard for diagnosis of endometriosis, observes Steven R. Goldstein, MD. Visualization of endometriotic implants at the time of surgery—with histologic assessment—offers definitive confirmation of the diagnosis. The physical examination, too, can offer a strong suggestion of endometriosis, he says. Dr. Goldstein is professor of obstetrics and gynecology at New York University School of Medicine and director of gynecologic ultrasound and co-director of bone densitometry at New York University Medical Center in New York City. He serves on the OBG Management Board of Editors.
“In the past, the pelvic examination and history often were the sine qua non for patients with pain,” Dr. Goldstein says. “Extreme dysmenorrhea and pain between periods, especially with intercourse, defecation, and exercise, all increased the suspicion of endometriosis. People used to talk about feeling nodularity in the uterosacral ligaments and finding decreased mobility of pelvic structures—but I don’t have any question that the skill of today’s gynecologists in doing a bimanual pelvic exam is a fraction of what it was in years gone by because they haven’t had the necessity of experience. The first thing they do if there’s any question is they send the patient for an ultrasound.”
Of course, ultrasound can be especially helpful in identifying endometriomas—sometimes called “chocolate cysts”—in the ovary. Endometriomas can have a solid appearance on ultrasound, says Dr. Goldstein, because the fluid they contain (dried blood) is sonolucent or pure black on ultrasound, similar to amniotic fluid or the fluid seen in the bladder. “This ‘chocolate’ fluid contained in endometriomas is homogeneous, particulate, and very monotonous in its appearance, in contrast to the internal echoes observed in hemorrhagic corpus lutea, which are very cobweblike and can sometimes mimic papillary projections,” he adds.
“What’s absolutely essential when imaging a suspected endometrioma by ultrasound is that there be no evidence of any blood flow contained within that structure. Because it’s dried blood, it shouldn’t have any vascularity. If you see blood flow inside what you would call an endometrioma, you need to rethink your diagnosis,” he says.
In some cases, a supposed endometriomalacks a black, sonolucent appearance, but “the clinician often can tell that it’s a cystic structure by the very bright posterior wall—what we call posterior wall acoustic enhancement—even though the interior of the structure may appear sort of grayish or whitish rather than the pure black of a simple cyst. It’s still fluid-filled,” Dr. Goldstein says.
In some instances, even endometriotic nodules can be imaged by ultrasound, he adds. “There’s an increasing body of literature that suggests that, if you look carefully in people with deep infiltrating endometriosis, you can often see solid-appearing nodules in the rectovaginal septum or between the uterus and bladder. With the kind of resolution that we now have with the vaginal probe, some of these nodules can be seen. That’s somewhat new, and it’s a function of 2 things—people looking for endometriosis and the better resolution of more modern equipment.”
Dr. Goldstein believes that magnetic resonance imaging (MRI) is “almost never” indicated in the diagnosis of endometriosis. A more helpful approach would be a consultative ultrasound with someone with more experience. However, when that is not available, or “in areas where you have excellent backup in terms of pelvic MRI, that may be the way to go. I don’t think so,” he demurs, “and some of my colleagues would be very upset at the thought of needing to use MRI to diagnose endometriosis. But in the occasional confusing or difficult case, depending on the quality of the referral pattern you have, it might make sense,” he says.
6. When is diagnostic laparoscopy clearly indicated?
Dr. Giudice believes that laparoscopy—with the intention to treat endometriosis, if present—“is essential when first-line medical therapy fails or when pain is acute and severe.”5
Dr. Stratton concurs. “Any woman with chronic pain wants to know what is causing the pain,” she says. Therefore, “women report a benefit from knowing that their pain is associated with endometriosis.6 However, diagnostic laparoscopy alone, with the sole purpose of determining the presence of endometriosis but not treating the lesions, is no longer performed, as it poses little benefit to the patient other than peace of mind.”
“The general trend in the United States has been to first use hormonal treatments when the diagnosis of endometriosis is suspected, prior to performing surgery,” Dr. Stratton says.1 In many cases, by using cyclic combined hormonal contraceptives to reduce menstrual flow or “suppressing menstruation with continuous combined hormonal contraceptives,” gonadotropin-releasing hormone analogues (combined with progestin to prevent bone loss), “or continuous progestin alone may be effective in decreasing pain. Not surprisingly, these hormonal approaches are effective for any chronic pelvic pain, even for women who do not have the surgical diagnosis of endometriosis.”20
“When the first-line approach to chronic pelvic pain is hormonal treatment, laparoscopy is considered when these medical treatments have failed to control the pain or are poorly tolerated, or when the diagnosis of endometriosis is in question,” Dr. Stratton says.
“Laparoscopy to treat endometriomas is indicated if an endometrioma is enlarging, measures more than 4 cm in diameter, or if the diagnosis of an ovarian mass is in question,” she explains. “While surgeons have previously been aggressive in removing endometriomas, this practice may have negative consequences on ovarian function. Because endometriomas are pseudocysts, removing them completely leads to the removal of viable ovarian tissue and may diminish ovarian reserve.”21,22
7. What is the surgical appearance of endometriosis?
Dr. Giudice returns to the enigmatic nature of endometriosis in addressing this question, mentioning its “many faces” at the time of surgery. “It is imperative that the surgeon recognize the disease in its many forms,” she says. “Also, it is especially helpful at the time of surgery if suspected lesions are biopsied and sent to pathology to have the diagnosis made unequivocally.”5
As for the surgical appearance of endometriosis, Dr. Stratton notes that there are 3 types of lesions—“superficial lesions, deep infiltrating lesions, and endometriomas. Endometriomas occur almost exclusively in the ovary and are pseudocysts without an identifiable cystic lining. They vary in dimension from a few millimeters to several centimeters.”
“Superficial peritoneal endometriosis lesions have a variable appearance, with some lesions being clear or red, some brown, blue or black, and some having a white appearance, like a scar,” says Dr. Stratton. “Endometriosis can be diagnosed on histologic examination of any of these lesion types.
“Overall, single-color lesions have similar frequencies of biopsy-confirmed endometriosis (59% to 62%),” she says.23 “These lesion appearances likely represent different stages of development of endometriosis, with red or clear lesions occurring first, soon after endometrial tissue implantation; black, blue, or brown lesions occurring later, in response to the hormones varying in the menstrual cycle; and white lesions occurring as the lesions age. Deep infiltrating lesions generally have blue/black or white features.”
“Wide, deep, multiple-color lesions in the cul-de-sac, ovarian fossa or uterosacral ligaments are most likely endometriosis,” Dr. Stratton adds.23 Only lesions with multiple colors have a significantly higher percentage of positive biopsies (76%). Importantly, over half of women with only subtle lesions (small red or white lesions) have endometriosis.
CASE Resolved
You tell the patient that endometriosis is one of the possible diagnoses for her chronic pelvic pain, and you take a focused history. During a pelvic examination, you observe that her right ovary lacks mobility, and you map a number of trigger points for her pain. Transvaginal ultrasound results suggest the presence of nodules in the rectovaginal septum. You begin empiric treatment with continuous combined hormonal contraceptives to suppress menstruation. On her next visit, the patient reports reduced but still bothersome pain. Laparoscopy reveals a 2-cm endometrioma in the right ovary and deep infiltrating lesions in the cul-de-sac. The endometrioma is resected. Histology confirms the diagnosis of endometriosis.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. American College of Obstetricians and Gynecologists. Practice Bulletin #114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–236.
2. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA. Endometriosis in association with uterine anomaly. Am J Obstet Gynecol. 1986;154(1):39–43.
3. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
4. Berkley KJ, Stratton P. Mechanisms: lessons from translational studies of endometriosis. In: Giamberardino MA, ed. Visceral Pain: Clinical, Pathophysiological and Therapeutic Aspects. Oxford, UK: Oxford University Press; 2009:39–50.
5. Giudice LC. Clinical practice: endometriosis. N Engl J Med. 2010;362(25):2389–2398.
6. Ballard K, Lowton K, Wright J. What’s the delay: a qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.
7. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.
8. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637–653.
9. Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155(12):4986–4999.
10. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715–2724.
11. De Graaff AA, D’Hooghe TM, Dunselman GA, et al. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677–2685.
12. Lafay Pillet MC, Huchon C, Santulli P, Borghese B, Chapron C, Fauconnier A. A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod. 2014;29(8):1666–1676.
13. Healey M, Cheng C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol. 2014;21(6):999–1004.
14. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis G, Noel JC. Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Invest. 2011;71(2):112–117.
15. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.
16. Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril. 2011;95(3):895–899.
17. Berkley KJ. A life of pelvic pain. Physiol Behav. 2005;86(3):272–280.
18. Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005;11(6):595–606.
19. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266–271.
20. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol. 1999;93(1):51–58.
21. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29(10):2190–2198.
22. Muzii L, Luciano AA, Zupi E, Panici PB. Effect of surgery for endometrioma on ovarian function: a different point of view. J Minim Invasive Gynecol. 2014;21(4):531–533.
23. Stegmann BJ, Sinaii N, Liu S, et al. Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women. Fertil Steril. 2008;89(6):1632–1636.
1. American College of Obstetricians and Gynecologists. Practice Bulletin #114: Management of endometriosis. Obstet Gynecol. 2010;116(1):223–236.
2. Sanfilippo JS, Wakim NG, Schikler KN, Yussman MA. Endometriosis in association with uterine anomaly. Am J Obstet Gynecol. 1986;154(1):39–43.
3. Taylor HS, Bagot C, Kardana A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331.
4. Berkley KJ, Stratton P. Mechanisms: lessons from translational studies of endometriosis. In: Giamberardino MA, ed. Visceral Pain: Clinical, Pathophysiological and Therapeutic Aspects. Oxford, UK: Oxford University Press; 2009:39–50.
5. Giudice LC. Clinical practice: endometriosis. N Engl J Med. 2010;362(25):2389–2398.
6. Ballard K, Lowton K, Wright J. What’s the delay: a qualitative study of women’s experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86(5):1296–1301.
7. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM. Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update. 2010;16(6):651–674.
8. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM. Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Hum Reprod Update. 2011;17(5):637–653.
9. Tamaresis JS, Irwin JC, Goldfien GA, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155(12):4986–4999.
10. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17(10):2715–2724.
11. De Graaff AA, D’Hooghe TM, Dunselman GA, et al. The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey. Hum Reprod. 2013;28(10):2677–2685.
12. Lafay Pillet MC, Huchon C, Santulli P, Borghese B, Chapron C, Fauconnier A. A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma. Hum Reprod. 2014;29(8):1666–1676.
13. Healey M, Cheng C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol. 2014;21(6):999–1004.
14. Anaf V, El Nakadi I, De Moor V, Chapron C, Pistofidis G, Noel JC. Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Invest. 2011;71(2):112–117.
15. Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update. 2011;17(3):327–346.
16. Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P. Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril. 2011;95(3):895–899.
17. Berkley KJ. A life of pelvic pain. Physiol Behav. 2005;86(3):272–280.
18. Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update. 2005;11(6):595–606.
19. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod. 2007;22(1):266–271.
20. Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Pelvic Pain Study Group. Obstet Gynecol. 1999;93(1):51–58.
21. Muzii L, Di Tucci C, Di Feliciantonio M, Marchetti C, Perniola G, Panici PB. The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis. Hum Reprod. 2014;29(10):2190–2198.
22. Muzii L, Luciano AA, Zupi E, Panici PB. Effect of surgery for endometrioma on ovarian function: a different point of view. J Minim Invasive Gynecol. 2014;21(4):531–533.
23. Stegmann BJ, Sinaii N, Liu S, et al. Using location, color, size, and depth to characterize and identify endometriosis lesions in a cohort of 133 women. Fertil Steril. 2008;89(6):1632–1636.
IN THIS ARTICLE
- The “why” of endometriosis
- Is imaging useful?
- When is diagnostic laparoscopy clearly indicated?
- Environmental factors, estrogen, and endometriosis
10 evidence-based recommendations to prevent surgical site infection after cesarean delivery
Infection is the second leading cause of pregnancy-related mortality in the United States, responsible for 13.6% of all maternal deaths.1 Cesarean delivery is the single most important risk factor for puerperal infection, increasing its incidence approximately 5- to 20-fold.2
Given that cesarean deliveries represent 32.7% of all births in the United States,3 the overall health and socioeconomic burden of these infections is substantial. In addition, more than half of all pregnancies are complicated by maternal obesity, which is associated with an increased risk of cesarean delivery as well as subsequent wound complications.4
In this review, we offer 10 evidence-based strategies to prevent surgical site infection (SSI) after cesarean delivery.
1 Maintain strict glycemic control in women with diabetes
Perioperative hyperglycemia is associated with an increased risk of postoperative infection in patients with diabetes
Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
Although data are limited on the impact of perioperative glycemic control on postcesarean infection rates, the association has been well documented in the general surgery literature. Results of a retrospective cohort study of 995 patients undergoing general or vascular surgery demonstrated that postoperative hyperglycemia increased the risk of infection by 30% for every 40-point increase in serum glucose levels from normoglycemia (defined as <110 mg/dL) (odds ratio, 1.3; 95% confidence interval [CI], 1.03–1.64).5 Hyperglycemia causes abnormalities of leukocyte function, including impaired granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. And all of these abnormalities in leukocyte function appear to improve with strict glycemic control, although the target range for blood glucose remains uncertain.6
2 Recommend preoperative antiseptic showering
Ask patients to shower with 4% chlorhexidine gluconate the night before surgery to reduce the presence of bacterial skin flora
Mangram AJ, Horan TC, Pearson ML, et al; Hospital Infection Control Practices Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):247–278.
Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
According to the Centers for Disease Control and Prevention, preoperative showering with chlorhexidine reduces the presence of bacterial skin flora. A study of more than 700 patients showed that preoperative showers with chlorhexidine reduced bacterial colony counts 9-fold, compared with only 1.3-fold for povidone-iodine.7 Whether this translates into a reduction in SSI remains controversial, in large part because of poor quality of the existing prospective trials, which used different agents, concentrations, and methods of skin preparation.8
Small clinical trials have found a benefit to chlorhexidine treatment the day before surgery.9,10 However, a recent meta-analysis of 16 randomized trials failed to show a significant reduction in the rate of SSI with chlorhexidine compared with soap, placebo, or no washing (relative risk [RR], 0.90; 95% CI, 0.77–1.05).11
3 Administer intravenous antibiotic prophylaxis
All patients who undergo cesarean delivery should be given appropriate antibiotic prophylaxis within 60 minutes before the skin incision
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of a single dose of a narrow-spectrum, first-generation cephalosporin (or a single dose of clindamycin with an aminoglycoside for those with a significant penicillin allergy) as SSI chemoprophylaxis for cesarean delivery.12 Due to concerns about fetal antibiotic exposure, such prophylaxis traditionally has been given after clamping of the umbilical cord. However, results of a recent meta-analysis of 5 randomized controlled trials demonstrated that antibiotic prophylaxis significantly reduced infectious morbidity (RR, 0.50; 95% CI, 0.33–0.78) when it was given 60 minutes before the skin incision, with no significant effect on neonatal outcome.13
4 Give a higher dose of preoperative antibiotics in obese women
Given the increased volume of distribution and the increased risk of postcesarean infection in the obese population, a higher dose of preoperative antibiotic prophylaxis is recommended
Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
The impact of maternal obesity on the risk of SSI after cesarean delivery was illustrated in a 2005 retrospective cohort study of 10,134 obese women. Moderately obese women with a prepregnancy weight of 90 to 100 kg were 1.6 times (95% CI, 1.31–1.95) more likely to have a wound infection, and severely obese women (>120 kg) were 4.45 times (95% CI, 3.00–6.61) more likely to have a wound infection after cesarean delivery, compared with women of normal weight.14
Moreover, a study of tissue concentrations of prophylactic cefazolin in obese women demonstrated that concentrations within adipose tissue at the site of the skin incision were inversely proportional to maternal body mass index (BMI).15 Given these findings, consideration should be given to using a higher dose of preoperative antibiotic prophylaxis in obese women, specifically 3 g of intravenous (IV) cefazolin for women with a BMI greater than 30 kg/m2 or an absolute weight of more than 100 kg.12
5 Use clippers for preoperative hair removal
If hair removal is necessary to perform the skin incision for cesarean delivery, the use of clippers is preferred
Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
In a Cochrane review of 3 randomized clinical trials comparing preoperative hair-removal techniques, shaving was associated with an increased risk of SSI, compared with clipping (RR, 2.09; 95% CI, 1.15–3.80).15 Shaving is thought to result in microscopic skin abrasions that can serve as foci for bacterial growth.
Interestingly, in this same Cochrane review, a separate analysis of 6 studies failed to show a benefit of preoperative hair removal by any means, compared with no hair removal,15 suggesting that routine hair removal may not be indicated for all patients.
6 Use chlorhexidine-alcohol for skin prep
Prepare the skin with chlorhexidine-alcohol immediately before surgery
Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
Data from a randomized multicenter trial of 849 patients showed that the use of a chlorhexidine-alcohol skin preparation immediately before surgery lowered the rate of SSI after clean-contaminated surgery, compared with povidone-iodine (RR, 0.59; 95% CI, 0.41–0.85).16 Studies focusing on cesarean delivery alone are limited, although 1 small randomized trial found that chlorhexidine treatment significantly reduced bacterial growth at 18 hours after cesarean, compared with povidone-iodine (RR, 0.23; 95% CI, 0.07–0.70).17
7 Consider an alcohol-based hand rub for preoperative antisepsis
Alcohol-based hand rubs may be more effective than conventional surgical scrub
Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
Several agents are available for preoperative surgical hand antisepsis, including newer alcohol-based rubs and conventional aqueous scrubs that contain either chlorhexidine gluconate or povidone-iodine. In a prospective cohort study of 128 health care providers, use of an alcohol-based rub for surgical hand antisepsis was associated with a lower rate of positive bacterial culture (6.2%), compared with a chlorhexidine-based conventional scrub (47.6%; P<.001).18 However, if an aqueous-based scrub is the only option available for surgical hand antisepsis, a Cochrane review found that chlorhexidine gluconate scrubs were more effective than povidone-iodine scrubs in 3 trials, resulting in fewer colony-forming units of bacteria on the hands of the surgical team.19
8 Close the skin with subcuticular sutures
Use of subcuticular sutures for skin closure is associated with a lower risk of wound complications, compared with staples
Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
A meta-analysis of 12 randomized controlled trials including 3,112 women demonstrated that subcuticular closure is associated with a decreased risk of wound complications, compared with staple closure (RR, 0.49; 95% CI, 0.28–0.87). The reduced risk remained significant even when stratified by obesity. Both closure techniques were shown to be equivalent with regard to postoperative pain, cosmetic outcome, and patient satisfaction.20
9 Close the subcutaneous tissue
Closure of the subcutaneous fat is associated with a decreased risk of wound disruption for women with a tissue thickness of more than 2 cm
Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
A meta-analysis of 5 randomized controlled trials demonstrated that suture closure of subcutaneous fat is associated with a 34% decrease in the risk of wound disruption in women with fat thickness greater than 2 cm (RR, 0.66; 95% CI, 0.48–0.91).21
A recent systematic review of evidence-based guidelines for surgical decisions during cesarean delivery also recommended this practice based on results of 9 published studies.22 In this review, however, subcutaneous drain placement did not offer any additional benefit, regardless of tissue thickness.22
10 Avoid unproven techniques
Several commonly performed techniques have not been associated with a decreased risk of SSI after cesarean delivery
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
CORONIS Trial Collaborative Group. The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial. BMC Pregnancy Childbirth. 2007;7:24. doi:10.1186/1471-2393-7-24.
Familiarity with the obstetric literature will help providers determine which interventions prevent SSI and which do not. Well-designed clinical studies have demonstrated no significant difference in the rate of postcesarean infectious morbidity with the administration of high concentrations of perioperative oxygen,22 saline wound irrigation,22 placement of subcutaneous drains,22 blunt versus sharp abdominal entry,23 and exteriorization of the uterus for repair.23
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006–2010. Obstet Gynecol. 2015;125(1):5–12.
2. Leth RA, Moller JK, Thomsen RW, Uldbjerg N, Norgaard M. Risk of selected postpartum infections after cesarean section compared with vaginal birth: a five-year cohort study of 32,468 women. Acta Obstet Gynecol Scand. 2009;88(9):976–983.
3. Martin JA, Hamilton BE, Osterman JK, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64(1):1–65.
4. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 549: Obesity in pregnancy. Obstet Gynecol. 2013;121(1):213–217.
5. Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
6. Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
7. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Hospital Infection Control Practices Advisory Committee: Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):250–278.
8. Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst Rev. 2012;9:CD004985.
9. Hayek LJ, Emerson JM, Gardner AM. A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on post-operative wound infection rates. J Hosp Infect. 1987;10(2):165–172.
10. Wihlborg O. The effect of washing with chlorhexidine soap on wound infection rate in general surgery: a controlled clinical study. Ann Chir Gynaecol. 1987;76(5):263–265.
11. Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
12. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
13. Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
14. Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
15. Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
16. Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
17. Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
18. Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
19. Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
20. Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
21. Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
22. Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 Pt 1):974–980.
23. Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
Infection is the second leading cause of pregnancy-related mortality in the United States, responsible for 13.6% of all maternal deaths.1 Cesarean delivery is the single most important risk factor for puerperal infection, increasing its incidence approximately 5- to 20-fold.2
Given that cesarean deliveries represent 32.7% of all births in the United States,3 the overall health and socioeconomic burden of these infections is substantial. In addition, more than half of all pregnancies are complicated by maternal obesity, which is associated with an increased risk of cesarean delivery as well as subsequent wound complications.4
In this review, we offer 10 evidence-based strategies to prevent surgical site infection (SSI) after cesarean delivery.
1 Maintain strict glycemic control in women with diabetes
Perioperative hyperglycemia is associated with an increased risk of postoperative infection in patients with diabetes
Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
Although data are limited on the impact of perioperative glycemic control on postcesarean infection rates, the association has been well documented in the general surgery literature. Results of a retrospective cohort study of 995 patients undergoing general or vascular surgery demonstrated that postoperative hyperglycemia increased the risk of infection by 30% for every 40-point increase in serum glucose levels from normoglycemia (defined as <110 mg/dL) (odds ratio, 1.3; 95% confidence interval [CI], 1.03–1.64).5 Hyperglycemia causes abnormalities of leukocyte function, including impaired granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. And all of these abnormalities in leukocyte function appear to improve with strict glycemic control, although the target range for blood glucose remains uncertain.6
2 Recommend preoperative antiseptic showering
Ask patients to shower with 4% chlorhexidine gluconate the night before surgery to reduce the presence of bacterial skin flora
Mangram AJ, Horan TC, Pearson ML, et al; Hospital Infection Control Practices Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):247–278.
Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
According to the Centers for Disease Control and Prevention, preoperative showering with chlorhexidine reduces the presence of bacterial skin flora. A study of more than 700 patients showed that preoperative showers with chlorhexidine reduced bacterial colony counts 9-fold, compared with only 1.3-fold for povidone-iodine.7 Whether this translates into a reduction in SSI remains controversial, in large part because of poor quality of the existing prospective trials, which used different agents, concentrations, and methods of skin preparation.8
Small clinical trials have found a benefit to chlorhexidine treatment the day before surgery.9,10 However, a recent meta-analysis of 16 randomized trials failed to show a significant reduction in the rate of SSI with chlorhexidine compared with soap, placebo, or no washing (relative risk [RR], 0.90; 95% CI, 0.77–1.05).11
3 Administer intravenous antibiotic prophylaxis
All patients who undergo cesarean delivery should be given appropriate antibiotic prophylaxis within 60 minutes before the skin incision
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of a single dose of a narrow-spectrum, first-generation cephalosporin (or a single dose of clindamycin with an aminoglycoside for those with a significant penicillin allergy) as SSI chemoprophylaxis for cesarean delivery.12 Due to concerns about fetal antibiotic exposure, such prophylaxis traditionally has been given after clamping of the umbilical cord. However, results of a recent meta-analysis of 5 randomized controlled trials demonstrated that antibiotic prophylaxis significantly reduced infectious morbidity (RR, 0.50; 95% CI, 0.33–0.78) when it was given 60 minutes before the skin incision, with no significant effect on neonatal outcome.13
4 Give a higher dose of preoperative antibiotics in obese women
Given the increased volume of distribution and the increased risk of postcesarean infection in the obese population, a higher dose of preoperative antibiotic prophylaxis is recommended
Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
The impact of maternal obesity on the risk of SSI after cesarean delivery was illustrated in a 2005 retrospective cohort study of 10,134 obese women. Moderately obese women with a prepregnancy weight of 90 to 100 kg were 1.6 times (95% CI, 1.31–1.95) more likely to have a wound infection, and severely obese women (>120 kg) were 4.45 times (95% CI, 3.00–6.61) more likely to have a wound infection after cesarean delivery, compared with women of normal weight.14
Moreover, a study of tissue concentrations of prophylactic cefazolin in obese women demonstrated that concentrations within adipose tissue at the site of the skin incision were inversely proportional to maternal body mass index (BMI).15 Given these findings, consideration should be given to using a higher dose of preoperative antibiotic prophylaxis in obese women, specifically 3 g of intravenous (IV) cefazolin for women with a BMI greater than 30 kg/m2 or an absolute weight of more than 100 kg.12
5 Use clippers for preoperative hair removal
If hair removal is necessary to perform the skin incision for cesarean delivery, the use of clippers is preferred
Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
In a Cochrane review of 3 randomized clinical trials comparing preoperative hair-removal techniques, shaving was associated with an increased risk of SSI, compared with clipping (RR, 2.09; 95% CI, 1.15–3.80).15 Shaving is thought to result in microscopic skin abrasions that can serve as foci for bacterial growth.
Interestingly, in this same Cochrane review, a separate analysis of 6 studies failed to show a benefit of preoperative hair removal by any means, compared with no hair removal,15 suggesting that routine hair removal may not be indicated for all patients.
6 Use chlorhexidine-alcohol for skin prep
Prepare the skin with chlorhexidine-alcohol immediately before surgery
Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
Data from a randomized multicenter trial of 849 patients showed that the use of a chlorhexidine-alcohol skin preparation immediately before surgery lowered the rate of SSI after clean-contaminated surgery, compared with povidone-iodine (RR, 0.59; 95% CI, 0.41–0.85).16 Studies focusing on cesarean delivery alone are limited, although 1 small randomized trial found that chlorhexidine treatment significantly reduced bacterial growth at 18 hours after cesarean, compared with povidone-iodine (RR, 0.23; 95% CI, 0.07–0.70).17
7 Consider an alcohol-based hand rub for preoperative antisepsis
Alcohol-based hand rubs may be more effective than conventional surgical scrub
Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
Several agents are available for preoperative surgical hand antisepsis, including newer alcohol-based rubs and conventional aqueous scrubs that contain either chlorhexidine gluconate or povidone-iodine. In a prospective cohort study of 128 health care providers, use of an alcohol-based rub for surgical hand antisepsis was associated with a lower rate of positive bacterial culture (6.2%), compared with a chlorhexidine-based conventional scrub (47.6%; P<.001).18 However, if an aqueous-based scrub is the only option available for surgical hand antisepsis, a Cochrane review found that chlorhexidine gluconate scrubs were more effective than povidone-iodine scrubs in 3 trials, resulting in fewer colony-forming units of bacteria on the hands of the surgical team.19
8 Close the skin with subcuticular sutures
Use of subcuticular sutures for skin closure is associated with a lower risk of wound complications, compared with staples
Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
A meta-analysis of 12 randomized controlled trials including 3,112 women demonstrated that subcuticular closure is associated with a decreased risk of wound complications, compared with staple closure (RR, 0.49; 95% CI, 0.28–0.87). The reduced risk remained significant even when stratified by obesity. Both closure techniques were shown to be equivalent with regard to postoperative pain, cosmetic outcome, and patient satisfaction.20
9 Close the subcutaneous tissue
Closure of the subcutaneous fat is associated with a decreased risk of wound disruption for women with a tissue thickness of more than 2 cm
Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
A meta-analysis of 5 randomized controlled trials demonstrated that suture closure of subcutaneous fat is associated with a 34% decrease in the risk of wound disruption in women with fat thickness greater than 2 cm (RR, 0.66; 95% CI, 0.48–0.91).21
A recent systematic review of evidence-based guidelines for surgical decisions during cesarean delivery also recommended this practice based on results of 9 published studies.22 In this review, however, subcutaneous drain placement did not offer any additional benefit, regardless of tissue thickness.22
10 Avoid unproven techniques
Several commonly performed techniques have not been associated with a decreased risk of SSI after cesarean delivery
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
CORONIS Trial Collaborative Group. The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial. BMC Pregnancy Childbirth. 2007;7:24. doi:10.1186/1471-2393-7-24.
Familiarity with the obstetric literature will help providers determine which interventions prevent SSI and which do not. Well-designed clinical studies have demonstrated no significant difference in the rate of postcesarean infectious morbidity with the administration of high concentrations of perioperative oxygen,22 saline wound irrigation,22 placement of subcutaneous drains,22 blunt versus sharp abdominal entry,23 and exteriorization of the uterus for repair.23
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Infection is the second leading cause of pregnancy-related mortality in the United States, responsible for 13.6% of all maternal deaths.1 Cesarean delivery is the single most important risk factor for puerperal infection, increasing its incidence approximately 5- to 20-fold.2
Given that cesarean deliveries represent 32.7% of all births in the United States,3 the overall health and socioeconomic burden of these infections is substantial. In addition, more than half of all pregnancies are complicated by maternal obesity, which is associated with an increased risk of cesarean delivery as well as subsequent wound complications.4
In this review, we offer 10 evidence-based strategies to prevent surgical site infection (SSI) after cesarean delivery.
1 Maintain strict glycemic control in women with diabetes
Perioperative hyperglycemia is associated with an increased risk of postoperative infection in patients with diabetes
Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
Although data are limited on the impact of perioperative glycemic control on postcesarean infection rates, the association has been well documented in the general surgery literature. Results of a retrospective cohort study of 995 patients undergoing general or vascular surgery demonstrated that postoperative hyperglycemia increased the risk of infection by 30% for every 40-point increase in serum glucose levels from normoglycemia (defined as <110 mg/dL) (odds ratio, 1.3; 95% confidence interval [CI], 1.03–1.64).5 Hyperglycemia causes abnormalities of leukocyte function, including impaired granulocyte adherence, impaired phagocytosis, delayed chemotaxis, and depressed bactericidal capacity. And all of these abnormalities in leukocyte function appear to improve with strict glycemic control, although the target range for blood glucose remains uncertain.6
2 Recommend preoperative antiseptic showering
Ask patients to shower with 4% chlorhexidine gluconate the night before surgery to reduce the presence of bacterial skin flora
Mangram AJ, Horan TC, Pearson ML, et al; Hospital Infection Control Practices Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):247–278.
Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
According to the Centers for Disease Control and Prevention, preoperative showering with chlorhexidine reduces the presence of bacterial skin flora. A study of more than 700 patients showed that preoperative showers with chlorhexidine reduced bacterial colony counts 9-fold, compared with only 1.3-fold for povidone-iodine.7 Whether this translates into a reduction in SSI remains controversial, in large part because of poor quality of the existing prospective trials, which used different agents, concentrations, and methods of skin preparation.8
Small clinical trials have found a benefit to chlorhexidine treatment the day before surgery.9,10 However, a recent meta-analysis of 16 randomized trials failed to show a significant reduction in the rate of SSI with chlorhexidine compared with soap, placebo, or no washing (relative risk [RR], 0.90; 95% CI, 0.77–1.05).11
3 Administer intravenous antibiotic prophylaxis
All patients who undergo cesarean delivery should be given appropriate antibiotic prophylaxis within 60 minutes before the skin incision
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
The American College of Obstetricians and Gynecologists (ACOG) recommends the use of a single dose of a narrow-spectrum, first-generation cephalosporin (or a single dose of clindamycin with an aminoglycoside for those with a significant penicillin allergy) as SSI chemoprophylaxis for cesarean delivery.12 Due to concerns about fetal antibiotic exposure, such prophylaxis traditionally has been given after clamping of the umbilical cord. However, results of a recent meta-analysis of 5 randomized controlled trials demonstrated that antibiotic prophylaxis significantly reduced infectious morbidity (RR, 0.50; 95% CI, 0.33–0.78) when it was given 60 minutes before the skin incision, with no significant effect on neonatal outcome.13
4 Give a higher dose of preoperative antibiotics in obese women
Given the increased volume of distribution and the increased risk of postcesarean infection in the obese population, a higher dose of preoperative antibiotic prophylaxis is recommended
Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
The impact of maternal obesity on the risk of SSI after cesarean delivery was illustrated in a 2005 retrospective cohort study of 10,134 obese women. Moderately obese women with a prepregnancy weight of 90 to 100 kg were 1.6 times (95% CI, 1.31–1.95) more likely to have a wound infection, and severely obese women (>120 kg) were 4.45 times (95% CI, 3.00–6.61) more likely to have a wound infection after cesarean delivery, compared with women of normal weight.14
Moreover, a study of tissue concentrations of prophylactic cefazolin in obese women demonstrated that concentrations within adipose tissue at the site of the skin incision were inversely proportional to maternal body mass index (BMI).15 Given these findings, consideration should be given to using a higher dose of preoperative antibiotic prophylaxis in obese women, specifically 3 g of intravenous (IV) cefazolin for women with a BMI greater than 30 kg/m2 or an absolute weight of more than 100 kg.12
5 Use clippers for preoperative hair removal
If hair removal is necessary to perform the skin incision for cesarean delivery, the use of clippers is preferred
Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
In a Cochrane review of 3 randomized clinical trials comparing preoperative hair-removal techniques, shaving was associated with an increased risk of SSI, compared with clipping (RR, 2.09; 95% CI, 1.15–3.80).15 Shaving is thought to result in microscopic skin abrasions that can serve as foci for bacterial growth.
Interestingly, in this same Cochrane review, a separate analysis of 6 studies failed to show a benefit of preoperative hair removal by any means, compared with no hair removal,15 suggesting that routine hair removal may not be indicated for all patients.
6 Use chlorhexidine-alcohol for skin prep
Prepare the skin with chlorhexidine-alcohol immediately before surgery
Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
Data from a randomized multicenter trial of 849 patients showed that the use of a chlorhexidine-alcohol skin preparation immediately before surgery lowered the rate of SSI after clean-contaminated surgery, compared with povidone-iodine (RR, 0.59; 95% CI, 0.41–0.85).16 Studies focusing on cesarean delivery alone are limited, although 1 small randomized trial found that chlorhexidine treatment significantly reduced bacterial growth at 18 hours after cesarean, compared with povidone-iodine (RR, 0.23; 95% CI, 0.07–0.70).17
7 Consider an alcohol-based hand rub for preoperative antisepsis
Alcohol-based hand rubs may be more effective than conventional surgical scrub
Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
Several agents are available for preoperative surgical hand antisepsis, including newer alcohol-based rubs and conventional aqueous scrubs that contain either chlorhexidine gluconate or povidone-iodine. In a prospective cohort study of 128 health care providers, use of an alcohol-based rub for surgical hand antisepsis was associated with a lower rate of positive bacterial culture (6.2%), compared with a chlorhexidine-based conventional scrub (47.6%; P<.001).18 However, if an aqueous-based scrub is the only option available for surgical hand antisepsis, a Cochrane review found that chlorhexidine gluconate scrubs were more effective than povidone-iodine scrubs in 3 trials, resulting in fewer colony-forming units of bacteria on the hands of the surgical team.19
8 Close the skin with subcuticular sutures
Use of subcuticular sutures for skin closure is associated with a lower risk of wound complications, compared with staples
Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
A meta-analysis of 12 randomized controlled trials including 3,112 women demonstrated that subcuticular closure is associated with a decreased risk of wound complications, compared with staple closure (RR, 0.49; 95% CI, 0.28–0.87). The reduced risk remained significant even when stratified by obesity. Both closure techniques were shown to be equivalent with regard to postoperative pain, cosmetic outcome, and patient satisfaction.20
9 Close the subcutaneous tissue
Closure of the subcutaneous fat is associated with a decreased risk of wound disruption for women with a tissue thickness of more than 2 cm
Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
A meta-analysis of 5 randomized controlled trials demonstrated that suture closure of subcutaneous fat is associated with a 34% decrease in the risk of wound disruption in women with fat thickness greater than 2 cm (RR, 0.66; 95% CI, 0.48–0.91).21
A recent systematic review of evidence-based guidelines for surgical decisions during cesarean delivery also recommended this practice based on results of 9 published studies.22 In this review, however, subcutaneous drain placement did not offer any additional benefit, regardless of tissue thickness.22
10 Avoid unproven techniques
Several commonly performed techniques have not been associated with a decreased risk of SSI after cesarean delivery
Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
CORONIS Trial Collaborative Group. The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial. BMC Pregnancy Childbirth. 2007;7:24. doi:10.1186/1471-2393-7-24.
Familiarity with the obstetric literature will help providers determine which interventions prevent SSI and which do not. Well-designed clinical studies have demonstrated no significant difference in the rate of postcesarean infectious morbidity with the administration of high concentrations of perioperative oxygen,22 saline wound irrigation,22 placement of subcutaneous drains,22 blunt versus sharp abdominal entry,23 and exteriorization of the uterus for repair.23
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006–2010. Obstet Gynecol. 2015;125(1):5–12.
2. Leth RA, Moller JK, Thomsen RW, Uldbjerg N, Norgaard M. Risk of selected postpartum infections after cesarean section compared with vaginal birth: a five-year cohort study of 32,468 women. Acta Obstet Gynecol Scand. 2009;88(9):976–983.
3. Martin JA, Hamilton BE, Osterman JK, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64(1):1–65.
4. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 549: Obesity in pregnancy. Obstet Gynecol. 2013;121(1):213–217.
5. Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
6. Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
7. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Hospital Infection Control Practices Advisory Committee: Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):250–278.
8. Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst Rev. 2012;9:CD004985.
9. Hayek LJ, Emerson JM, Gardner AM. A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on post-operative wound infection rates. J Hosp Infect. 1987;10(2):165–172.
10. Wihlborg O. The effect of washing with chlorhexidine soap on wound infection rate in general surgery: a controlled clinical study. Ann Chir Gynaecol. 1987;76(5):263–265.
11. Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
12. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
13. Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
14. Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
15. Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
16. Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
17. Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
18. Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
19. Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
20. Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
21. Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
22. Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 Pt 1):974–980.
23. Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
1. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006–2010. Obstet Gynecol. 2015;125(1):5–12.
2. Leth RA, Moller JK, Thomsen RW, Uldbjerg N, Norgaard M. Risk of selected postpartum infections after cesarean section compared with vaginal birth: a five-year cohort study of 32,468 women. Acta Obstet Gynecol Scand. 2009;88(9):976–983.
3. Martin JA, Hamilton BE, Osterman JK, et al. Births: final data for 2013. Natl Vital Stat Rep. 2015;64(1):1–65.
4. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 549: Obesity in pregnancy. Obstet Gynecol. 2013;121(1):213–217.
5. Dahlke JD, Mendez-Figueroa H, Rouse DJ, Berghella V, Baxter JK, Chauhan SP. Evidence-based surgery for cesarean delivery: an updated systematic review. Am J Obstet Gynecol. 2013;209(4):294–306.
6. Ramos M, Khalpey Z, Lipsitz S, et al. Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248(4):585–591.
7. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Hospital Infection Control Practices Advisory Committee: Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20(4):250–278.
8. Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst Rev. 2012;9:CD004985.
9. Hayek LJ, Emerson JM, Gardner AM. A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on post-operative wound infection rates. J Hosp Infect. 1987;10(2):165–172.
10. Wihlborg O. The effect of washing with chlorhexidine soap on wound infection rate in general surgery: a controlled clinical study. Ann Chir Gynaecol. 1987;76(5):263–265.
11. Chlebicki MP, Safdar N, O’Horo JC, Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis. Am J Infect Control. 2013;41(2):167–173.
12. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472–1483.
13. Costantine MM, Rahman M, Ghulmiyah L, et al. Timing of perioperative antibiotics for cesarean delivery: a meta-analysis. Am J Obstet Gynecol. 2008;199(3):301.e1–e6.
14. Robinson HE, O’Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol. 2005;106(6):1357–1364.
15. Pevzner L, Swank M, Krepel C, et al. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011;117(4):877–882.
16. Tanner J, Norrie P, Melen K. Preoperative hair removal to reduce surgical site infection. Cochrane Database Syst Rev. 2011;11:CD004122.
17. Darouiche RO, Wall MJ Jr, Itani KM, et al. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26.
18. Kunkle CM, Marchan J, Safadi S, Whitman S, Chmait RH. Chlorhexidine gluconate versus povidone iodine at cesarean delivery: a randomized controlled trial. J Matern Fetal Neonatal Med. 2014;18:1–5.
19. Shen NJ, Pan SC, Sheng WH, et al. Comparative antimicrobial efficacy of alcohol-based hand rub and conventional surgical scrub in a medical center [published online ahead of print September 21, 2013]. J Microbiol Immunol Infect. pii:S1684–1182(13)00150–3.
20. Tanner J, Swarbrook S, Stuart J. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev. 2008;1:CD004288.
21. Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a meta-analysis [published online ahead of print December 19, 2014]. Am J Obstet Gynecol. doi:10.1016/j.ajog.2014.12.020.
22. Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 Pt 1):974–980.
23. Hanazaki K, Maeda H, Okabayashi T. Relationship between perioperative glycemic control and postoperative infections. World J Gastroenterol. 2009;15(33):4122–4125.
2015 Update on minimally invasive gynecologic surgery
Office hysteroscopy offers many benefits and is becoming more acceptable among patients and gynecologists for both diagnostic and operative procedures (TABLE 1). Despite its clear advantages, however, many gynecologists remain hesitant to perform in-office procedures out of fear that the patient, who is generally awake, will experience significant discomfort.
Certainly, pain and low patient tolerance of discomfort have been the primary limitations to widespread use of office hysteroscopy without anesthesia.1 Data on the use of anesthesia for office hysteroscopy—especially diagnostic procedures—historically have been inconsistent in regard to the reduction of patient discomfort.2
Bettocchi and Selvaggi first reported a vaginoscopic approach to diagnostic hysteroscopy to reduce the discomfort of the procedure, compared with the conventional approach. They did not place a vaginal speculum or tenaculum and, therefore, avoided placing local anesthetic into the cervix.3
A randomized controlled trial by Sagiv and colleagues found reduced pain during diagnostic hysteroscopy with vaginoscopy (VIDEO).4

In 2004, Bettocchi and colleagues reported nearly 5,000 operative hysteroscopic procedures performed with this technique (the “no-touch” technique) in an outpatient setting, demonstrating very high patient tolerance and a low degree of procedural pain. More than 90% of patients experienced little to no pain, except for those undergoing polypectomy when the polyps were larger than the diameter of the cervical os, as well as those who had anatomic abnormalities, with moderate discomfort reported by 33.2% and 12.7% of these women, respectively.5 These few patients may have benefited from anesthetic intervention for the procedure.
In a 2010 review of the literature on hysteroscopy without anesthesia, Cicinelli found that diagnostic hysteroscopy was more successful, with less patient discomfort, when smaller hysteroscopes were used (3.5 mm or smaller, including flexible lenses) and when the approach was vaginoscopic.1 Reduced pain with operative procedures was associated with a number of variables, including:
- increased surgeon experience
- smaller instrument size
- shorter duration of the procedure
- premenopausal status.
Variables associated with increased pain during operative procedures included:
- chronic pelvic pain
- menopausal status
- previous cesarean delivery
- significant anxiety.
In the review, Cicinelli noted that not all patients are likely to have a successful hysteroscopic procedure without the use of anesthesia or analgesia, regardless of the approach used.1
Only 1 randomized controlled trial explored the use of anesthesia (versus placebo) during operative hysteroscopy, and the authors found a benefit for preprocedural paracervical block using local anesthetic to reduce cervical pain.6
The success of diagnostic and operative hysteroscopic procedures with minimal and acceptable levels of patient discomfort in the office depends, therefore, on multiple factors. Procedural factors affecting the outcome of hysteroscopy include the size of the instrument used, the type and length of the procedure, the use of preprocedure anesthesia or analgesia, and a vaginoscopic approach. The skill of the surgeon also affects the hysteroscopic experience and outcome. In addition, patient variables such as menopausal status, anatomic distortion (eg, cervical stenosis), and anxiety may adversely affect the patient’s experience.
In summary, it is possible for the gynecologist to appropriately accommodate any given patient and clinical scenario, keeping in mind that many patients will require a customized approach for ultimate success. In this article, I review 3 recent studies on office hysteroscopy, focusing on the reduction of procedural pain and anxiety. Because of the protective effect of a high degree of surgeon experience, it is important that we offer adequate education in hysteroscopy during residency and postgraduate courses.
Placement of local anesthetic at multiple anatomic sites facilitates patient comfort during hysteroscopy
Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
In a 2010 review of randomized controlled trials of the use of local anesthesia versus placebo during hysteroscopy, data from several studies indicated a significant decrease in procedural pain when local anesthesia was given, while other studies found no difference.2 Most of the studies in that review evaluated a single site of anesthesia placement and focused on diagnostic hysteroscopy. The findings of that review, as well as the differential innervation of the uterine cervix and fundus (FIGURE), prompted Keyhan and Munro to evaluate the efficacy of multimodal local anesthetic for office diagnostic and operative hysteroscopy without the use of any systemic agents except for preprocedural cyclooxygenase (COX) inhibitors (TABLE 2). Accordingly, they placed local anesthetic at multiple anatomic sites to alleviate patient pain and improve procedural success in a spectrum of office-based hysteroscopic procedures.
Details of the trial
Procedures generally were performed using a continuous-flow sheath with an outside diameter of 5.5 mm and a 5 French operative channel for placement of operative instruments such as scissors, graspers, and sterilization microinserts. Normal saline or sterile water was used as the uterine distention medium, with gravity inflow assisted by pressure cuff, when necessary. Occasionally, a sheath system with an outside diameter of 6.5 mm was used, or an outside diameter of 9 mm for resectoscopic procedures using a bipolar radiofrequency resectoscope. When needed, cervical dilation was performed to accommodate the specific instrument used.
The impact of the multimodal, multisite anesthetic protocol was evaluated using contemporaneous patient reporting of numeric pain scores (worst pain experienced) that included anesthesia-related pain, procedure-related pain, and overall pain.
A total of 478 women underwent 535 procedures. A patient verbal response scale (range, 0–10) was used to assess the worst pain experienced. The overall mean (SD) procedure pain score was 3.7 (2.5). The mean score for patients undergoing diagnostic hysteroscopy was 3.2 (2.5), and it was 4.1 (2.5) for operative hysteroscopy (P<.001).
TABLE 3 shows the procedures performed under the anesthetic protocol. Pain associated with placement of anesthesia was similar for diagnostic and operative procedures (mean score, 2.7), but the mean overall pain scores for diagnostic procedures were about 1 unit less than for operative procedures, regardless of age or delivery history.
Complications were limited to 3 transient vasovagal episodes. Five procedures could not be completed because of intolerable pain or inability to access the uterine cavity. There was no difference in pain scores between menopausal and premeno-pausal women.
Malcolm G. Munro, MD, offers a protocol for pain relief during hysteroscopy
In this video, Malcolm G. Munro, MD, makes use of both topical and injectable lidocaine at 5 anatomic sites
Dr. Munro is Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA and Director of Gynecologic Services at Kaiser Permanente, Los Angeles Medical Center, in Los Angeles, California.
When placing anesthesia at multiple sites, allow time for onset of action
Keyhan and Munro demonstrated that successful completion of hysteroscopic procedures in the office environment can be achieved with acceptable levels of patient discomfort using a multimodal, multisite approach for preemptive placement of local anesthetic in the vagina, cervix, and endometrial cavity. They emphasize that the waiting time allotted for the onset of anesthesia is critical to the success of this approach. They also stress that no preprocedure oral sedative or narcotic is used with their approach. In addition, they note that the minimal discomfort experienced during placement of local anesthetic was overshadowed by general comfort during the wide spectrum of procedures performed.
What this EVIDENCE means for practice
The placement of preemptive local anesthesia at multiple anatomic sites facilitates diagnostic and operative hysteroscopy with an acceptable degree of patient comfort and successful completion of office procedures.
Music may reduce patient anxiety during hysteroscopy
Angioli R, De Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
Angioli and colleagues set out to address another factor that can impede patient comfort during office hysteroscopy—anxiety. Their randomized prospective trial is the only such trial evaluating the use of music to establish a calm and relaxing environment prior to office hysteroscopy for patients who are awake. Music supports an environment that “stimulates and maintains relaxation, well-being, and comfort and can be used as a self-management technique to reduce or control distress,” Angioli and colleagues write. The theory is that music distracts the patient by drawing her attention away from negative stimuli, thereby reducing pain, anxiety, and stress.
Details of the trial
A standardized visual analog scale (range, 0–10) was used to assess patient discomfort, and a State-Trait Anxiety Inventory (STAI; range, 20–80) also was given. Both tools were administered at baseline. The visual analog scale was measured again during the procedure, and the STAI was administered again after the procedure.
A hysteroscopic sheath with an outside diameter of 5 mm was used with a 5 French operative channel, and a vaginoscopic approach was used for each hysteroscopic procedure. A total of 372 women were enrolled and randomly allocated to either:
- music group (n = 185)
- no-music group (n = 187).
The surgical procedure was not completed in 15 patients (9 in the music group and 6 in the no-music group) because of stenosis of the cervix and/or excessive pain.
Women in the music group were allowed to select a playlist of classical, pop, jazz, or rock music that was played through a speaker system in the room. Of these patients, 50% preferred classical, 45% preferred pop, 5% chose jazz, and none selected rock music.
There were no statistically significant differences between the 2 groups in terms of preprocedure wait time, preprocedure scores on the visual analog scale or STAI, preprocedure vital signs, patient characteristics, type of procedure, or duration of the procedure. However, the music group had a lower visual analog score during the procedure and a lower postoperative STAI for diagnostic hysteroscopy than the no-music group did. The music group also had a statistically significant lower visual analog score for operative hysteroscopy than the no-music group did. In addition, the music group had a lower postoperative STAI score than the no-music group, but this difference was not statistically significant (TABLE 4).
Interestingly, in the music group, the STAI scores were lower after both diagnostic and operative hysteroscopy when classical music was selected rather than pop music.
Anxiety and pain are highly correlated
Angioli and colleagues found that patients who listened to music intraoperatively had a lower perception of pain and less anxiety. In addition, systolic blood pressure and heart rate were significantly lower in the music group than the no-music group, implying that patients who listened to music experienced less physical stress during the procedure.
Angioli and colleagues also noted that the level of anxiety and perception of pain were highly correlated. Pain is not an emotionally neutral experience but is almost always accompanied by distress. Investigators concluded that “anxiety can enhance painful sensations at all levels of the nervous system, from the peripheral receptors to the cortical level.”
What this EVIDENCE means for practice
Music is a useful complementary method to control patient anxiety and reduce the perception of pain during office hysteroscopy by creating a more relaxed and comfortable environment.
What are the risk factors for pain and discomfort during office hysteroscopy?
De Freitas FM, Sessa FV, Resende AD Jr, et al. Identifying predictors of unacceptable pain at office hysteroscopy. J Minim Invasive Gynecol. 2014;21(4):586–591.
De Freitas and colleagues conducted their prospective observational study to identify predictors of unacceptable pain during diagnostic office hysteroscopy (with or without directed or curette endometrial biopsy) and at the time of discharge. They hoped that any identifiable causes of unacceptable pain could be addressed individually in future patients undergoing office hysteroscopy to reduce their level of discomfort.
Details of the trial
A total of 558 procedures were evaluated. Hysteroscopists had varying levels of experience, with some having performed fewer than 50 procedures and others having performed more than 500.
A verbal response scale (range, 0–10) was used to assess pain at the end of each procedure and at the time of discharge. Investigators considered a score of 7 or more at the time of the procedure and a score of 4 or more at the time of discharge to be unacceptable.
A diagnostic, single-channel hysteroscope with an outside diameter of 3.5 mm was used with normal saline (at room temperature), along with a gravity system with pressure established to maintain intrauterine pressure at approximately 110 mm Hg. All hysteroscopic procedures were performed using a vaginoscopic approach, and biopsies were obtained as clinically indicated. Any patients who reported cramping at discharge (ie, a verbal response scale score of 4 or more) were offered an oral nonsteroidal anti-inflammatory drug.
Overall, the prevalence of unacceptable pain during office hysteroscopy was 32.3%. Experience of the hysteroscopist had a significant protective effect against pain. Longer procedures were significantly associated with unacceptable procedural pain.
The prevalence of unacceptable cramping at discharge was 28.6%. The risk of discomfort at discharge was significantly higher for women who reported dyspareunia or dysmenorrhea. Surgeon experience was significantly protective against unacceptable pain at discharge, and longer procedures were significantly associated with increased discomfort at discharge.
Dysmenorrhea and dyspareunia were significant predictors of pain at discharge
In this study, dysmenorrhea was a significant predictor of unacceptable pain at discharge, increasing the risk of unacceptable cramps by approximately threefold. Women who reported dyspareunia were nearly twice as likely to report unacceptable cramping at discharge.
Although a high level of expertise is not a prerequisite for office hysteroscopy, the skill and experience of the hysteroscopist, as well as shorter procedures, proved to be protective against procedural pain and discomfort at discharge but did not eliminate them altogether. Therefore, De Freitas and colleagues recommend that patients who can be identified as high-risk for procedural or discharge pain, such as women with dysmenorrhea or dyspareunia, should be offered preprocedure analgesia and/or anesthesia to reduce overall discomfort.
What this EVIDENCE means for practice
If a patient reports dysmenorrhea or dyspareunia preoperatively, she may benefit from preprocedure anesthesia or analgesia, or both, in an office setting.
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
1. Cicinelli E. Hysteroscopy without anesthesia: review of recent literature. J Minim Invasive Gynecol. 2010;17(6):703–708.
2. Munro MG, Brooks PG. Use of local anesthesia for office diagnostic and operative hysteroscopy. J Minim Invasive Gynecol. 2010;17(6):709–718.
3. Bettocchi S, Selvaggi L. A vaginoscopic approach to reduce the pain of office hysteroscopy. J Am Assoc Gynecol Laparosc. 1997;4(2):255–258.
4. Sagiv R, Sadan O, Boaz M, et al. A new approach to office hysteroscopy compared with traditional hysteroscopy. A randomized controlled trial. Am J Obstet Gynecol. 2006;108(2):387–392.
5.Bettocchi S, Ceci O, Nappi L, et al. Operative office hysteroscopy without anesthesia: analysis of 4,863 cases performed with mechanical instruments. J Am Assoc Gynecol Laparosc. 2004;11(1):59–61.
6. Chudnoff S, Einstein M, Levie M. Paracervical block efficacy in office hysteroscopic sterilization. A randomized controlled trial. Obstet Gynecol. 2010;115(1):26–34.
7. Garcia AL. Stop performing dilation and curettage for the evaluation of abnormal uterine bleeding. OBG Manag. 2013;25(6):44–48.
8. Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
9. Angioli R, de Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
Office hysteroscopy offers many benefits and is becoming more acceptable among patients and gynecologists for both diagnostic and operative procedures (TABLE 1). Despite its clear advantages, however, many gynecologists remain hesitant to perform in-office procedures out of fear that the patient, who is generally awake, will experience significant discomfort.
Certainly, pain and low patient tolerance of discomfort have been the primary limitations to widespread use of office hysteroscopy without anesthesia.1 Data on the use of anesthesia for office hysteroscopy—especially diagnostic procedures—historically have been inconsistent in regard to the reduction of patient discomfort.2
Bettocchi and Selvaggi first reported a vaginoscopic approach to diagnostic hysteroscopy to reduce the discomfort of the procedure, compared with the conventional approach. They did not place a vaginal speculum or tenaculum and, therefore, avoided placing local anesthetic into the cervix.3
A randomized controlled trial by Sagiv and colleagues found reduced pain during diagnostic hysteroscopy with vaginoscopy (VIDEO).4

In 2004, Bettocchi and colleagues reported nearly 5,000 operative hysteroscopic procedures performed with this technique (the “no-touch” technique) in an outpatient setting, demonstrating very high patient tolerance and a low degree of procedural pain. More than 90% of patients experienced little to no pain, except for those undergoing polypectomy when the polyps were larger than the diameter of the cervical os, as well as those who had anatomic abnormalities, with moderate discomfort reported by 33.2% and 12.7% of these women, respectively.5 These few patients may have benefited from anesthetic intervention for the procedure.
In a 2010 review of the literature on hysteroscopy without anesthesia, Cicinelli found that diagnostic hysteroscopy was more successful, with less patient discomfort, when smaller hysteroscopes were used (3.5 mm or smaller, including flexible lenses) and when the approach was vaginoscopic.1 Reduced pain with operative procedures was associated with a number of variables, including:
- increased surgeon experience
- smaller instrument size
- shorter duration of the procedure
- premenopausal status.
Variables associated with increased pain during operative procedures included:
- chronic pelvic pain
- menopausal status
- previous cesarean delivery
- significant anxiety.
In the review, Cicinelli noted that not all patients are likely to have a successful hysteroscopic procedure without the use of anesthesia or analgesia, regardless of the approach used.1
Only 1 randomized controlled trial explored the use of anesthesia (versus placebo) during operative hysteroscopy, and the authors found a benefit for preprocedural paracervical block using local anesthetic to reduce cervical pain.6
The success of diagnostic and operative hysteroscopic procedures with minimal and acceptable levels of patient discomfort in the office depends, therefore, on multiple factors. Procedural factors affecting the outcome of hysteroscopy include the size of the instrument used, the type and length of the procedure, the use of preprocedure anesthesia or analgesia, and a vaginoscopic approach. The skill of the surgeon also affects the hysteroscopic experience and outcome. In addition, patient variables such as menopausal status, anatomic distortion (eg, cervical stenosis), and anxiety may adversely affect the patient’s experience.
In summary, it is possible for the gynecologist to appropriately accommodate any given patient and clinical scenario, keeping in mind that many patients will require a customized approach for ultimate success. In this article, I review 3 recent studies on office hysteroscopy, focusing on the reduction of procedural pain and anxiety. Because of the protective effect of a high degree of surgeon experience, it is important that we offer adequate education in hysteroscopy during residency and postgraduate courses.
Placement of local anesthetic at multiple anatomic sites facilitates patient comfort during hysteroscopy
Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
In a 2010 review of randomized controlled trials of the use of local anesthesia versus placebo during hysteroscopy, data from several studies indicated a significant decrease in procedural pain when local anesthesia was given, while other studies found no difference.2 Most of the studies in that review evaluated a single site of anesthesia placement and focused on diagnostic hysteroscopy. The findings of that review, as well as the differential innervation of the uterine cervix and fundus (FIGURE), prompted Keyhan and Munro to evaluate the efficacy of multimodal local anesthetic for office diagnostic and operative hysteroscopy without the use of any systemic agents except for preprocedural cyclooxygenase (COX) inhibitors (TABLE 2). Accordingly, they placed local anesthetic at multiple anatomic sites to alleviate patient pain and improve procedural success in a spectrum of office-based hysteroscopic procedures.
Details of the trial
Procedures generally were performed using a continuous-flow sheath with an outside diameter of 5.5 mm and a 5 French operative channel for placement of operative instruments such as scissors, graspers, and sterilization microinserts. Normal saline or sterile water was used as the uterine distention medium, with gravity inflow assisted by pressure cuff, when necessary. Occasionally, a sheath system with an outside diameter of 6.5 mm was used, or an outside diameter of 9 mm for resectoscopic procedures using a bipolar radiofrequency resectoscope. When needed, cervical dilation was performed to accommodate the specific instrument used.
The impact of the multimodal, multisite anesthetic protocol was evaluated using contemporaneous patient reporting of numeric pain scores (worst pain experienced) that included anesthesia-related pain, procedure-related pain, and overall pain.
A total of 478 women underwent 535 procedures. A patient verbal response scale (range, 0–10) was used to assess the worst pain experienced. The overall mean (SD) procedure pain score was 3.7 (2.5). The mean score for patients undergoing diagnostic hysteroscopy was 3.2 (2.5), and it was 4.1 (2.5) for operative hysteroscopy (P<.001).
TABLE 3 shows the procedures performed under the anesthetic protocol. Pain associated with placement of anesthesia was similar for diagnostic and operative procedures (mean score, 2.7), but the mean overall pain scores for diagnostic procedures were about 1 unit less than for operative procedures, regardless of age or delivery history.
Complications were limited to 3 transient vasovagal episodes. Five procedures could not be completed because of intolerable pain or inability to access the uterine cavity. There was no difference in pain scores between menopausal and premeno-pausal women.
Malcolm G. Munro, MD, offers a protocol for pain relief during hysteroscopy
In this video, Malcolm G. Munro, MD, makes use of both topical and injectable lidocaine at 5 anatomic sites
Dr. Munro is Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA and Director of Gynecologic Services at Kaiser Permanente, Los Angeles Medical Center, in Los Angeles, California.
When placing anesthesia at multiple sites, allow time for onset of action
Keyhan and Munro demonstrated that successful completion of hysteroscopic procedures in the office environment can be achieved with acceptable levels of patient discomfort using a multimodal, multisite approach for preemptive placement of local anesthetic in the vagina, cervix, and endometrial cavity. They emphasize that the waiting time allotted for the onset of anesthesia is critical to the success of this approach. They also stress that no preprocedure oral sedative or narcotic is used with their approach. In addition, they note that the minimal discomfort experienced during placement of local anesthetic was overshadowed by general comfort during the wide spectrum of procedures performed.
What this EVIDENCE means for practice
The placement of preemptive local anesthesia at multiple anatomic sites facilitates diagnostic and operative hysteroscopy with an acceptable degree of patient comfort and successful completion of office procedures.
Music may reduce patient anxiety during hysteroscopy
Angioli R, De Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
Angioli and colleagues set out to address another factor that can impede patient comfort during office hysteroscopy—anxiety. Their randomized prospective trial is the only such trial evaluating the use of music to establish a calm and relaxing environment prior to office hysteroscopy for patients who are awake. Music supports an environment that “stimulates and maintains relaxation, well-being, and comfort and can be used as a self-management technique to reduce or control distress,” Angioli and colleagues write. The theory is that music distracts the patient by drawing her attention away from negative stimuli, thereby reducing pain, anxiety, and stress.
Details of the trial
A standardized visual analog scale (range, 0–10) was used to assess patient discomfort, and a State-Trait Anxiety Inventory (STAI; range, 20–80) also was given. Both tools were administered at baseline. The visual analog scale was measured again during the procedure, and the STAI was administered again after the procedure.
A hysteroscopic sheath with an outside diameter of 5 mm was used with a 5 French operative channel, and a vaginoscopic approach was used for each hysteroscopic procedure. A total of 372 women were enrolled and randomly allocated to either:
- music group (n = 185)
- no-music group (n = 187).
The surgical procedure was not completed in 15 patients (9 in the music group and 6 in the no-music group) because of stenosis of the cervix and/or excessive pain.
Women in the music group were allowed to select a playlist of classical, pop, jazz, or rock music that was played through a speaker system in the room. Of these patients, 50% preferred classical, 45% preferred pop, 5% chose jazz, and none selected rock music.
There were no statistically significant differences between the 2 groups in terms of preprocedure wait time, preprocedure scores on the visual analog scale or STAI, preprocedure vital signs, patient characteristics, type of procedure, or duration of the procedure. However, the music group had a lower visual analog score during the procedure and a lower postoperative STAI for diagnostic hysteroscopy than the no-music group did. The music group also had a statistically significant lower visual analog score for operative hysteroscopy than the no-music group did. In addition, the music group had a lower postoperative STAI score than the no-music group, but this difference was not statistically significant (TABLE 4).
Interestingly, in the music group, the STAI scores were lower after both diagnostic and operative hysteroscopy when classical music was selected rather than pop music.
Anxiety and pain are highly correlated
Angioli and colleagues found that patients who listened to music intraoperatively had a lower perception of pain and less anxiety. In addition, systolic blood pressure and heart rate were significantly lower in the music group than the no-music group, implying that patients who listened to music experienced less physical stress during the procedure.
Angioli and colleagues also noted that the level of anxiety and perception of pain were highly correlated. Pain is not an emotionally neutral experience but is almost always accompanied by distress. Investigators concluded that “anxiety can enhance painful sensations at all levels of the nervous system, from the peripheral receptors to the cortical level.”
What this EVIDENCE means for practice
Music is a useful complementary method to control patient anxiety and reduce the perception of pain during office hysteroscopy by creating a more relaxed and comfortable environment.
What are the risk factors for pain and discomfort during office hysteroscopy?
De Freitas FM, Sessa FV, Resende AD Jr, et al. Identifying predictors of unacceptable pain at office hysteroscopy. J Minim Invasive Gynecol. 2014;21(4):586–591.
De Freitas and colleagues conducted their prospective observational study to identify predictors of unacceptable pain during diagnostic office hysteroscopy (with or without directed or curette endometrial biopsy) and at the time of discharge. They hoped that any identifiable causes of unacceptable pain could be addressed individually in future patients undergoing office hysteroscopy to reduce their level of discomfort.
Details of the trial
A total of 558 procedures were evaluated. Hysteroscopists had varying levels of experience, with some having performed fewer than 50 procedures and others having performed more than 500.
A verbal response scale (range, 0–10) was used to assess pain at the end of each procedure and at the time of discharge. Investigators considered a score of 7 or more at the time of the procedure and a score of 4 or more at the time of discharge to be unacceptable.
A diagnostic, single-channel hysteroscope with an outside diameter of 3.5 mm was used with normal saline (at room temperature), along with a gravity system with pressure established to maintain intrauterine pressure at approximately 110 mm Hg. All hysteroscopic procedures were performed using a vaginoscopic approach, and biopsies were obtained as clinically indicated. Any patients who reported cramping at discharge (ie, a verbal response scale score of 4 or more) were offered an oral nonsteroidal anti-inflammatory drug.
Overall, the prevalence of unacceptable pain during office hysteroscopy was 32.3%. Experience of the hysteroscopist had a significant protective effect against pain. Longer procedures were significantly associated with unacceptable procedural pain.
The prevalence of unacceptable cramping at discharge was 28.6%. The risk of discomfort at discharge was significantly higher for women who reported dyspareunia or dysmenorrhea. Surgeon experience was significantly protective against unacceptable pain at discharge, and longer procedures were significantly associated with increased discomfort at discharge.
Dysmenorrhea and dyspareunia were significant predictors of pain at discharge
In this study, dysmenorrhea was a significant predictor of unacceptable pain at discharge, increasing the risk of unacceptable cramps by approximately threefold. Women who reported dyspareunia were nearly twice as likely to report unacceptable cramping at discharge.
Although a high level of expertise is not a prerequisite for office hysteroscopy, the skill and experience of the hysteroscopist, as well as shorter procedures, proved to be protective against procedural pain and discomfort at discharge but did not eliminate them altogether. Therefore, De Freitas and colleagues recommend that patients who can be identified as high-risk for procedural or discharge pain, such as women with dysmenorrhea or dyspareunia, should be offered preprocedure analgesia and/or anesthesia to reduce overall discomfort.
What this EVIDENCE means for practice
If a patient reports dysmenorrhea or dyspareunia preoperatively, she may benefit from preprocedure anesthesia or analgesia, or both, in an office setting.
Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Office hysteroscopy offers many benefits and is becoming more acceptable among patients and gynecologists for both diagnostic and operative procedures (TABLE 1). Despite its clear advantages, however, many gynecologists remain hesitant to perform in-office procedures out of fear that the patient, who is generally awake, will experience significant discomfort.
Certainly, pain and low patient tolerance of discomfort have been the primary limitations to widespread use of office hysteroscopy without anesthesia.1 Data on the use of anesthesia for office hysteroscopy—especially diagnostic procedures—historically have been inconsistent in regard to the reduction of patient discomfort.2
Bettocchi and Selvaggi first reported a vaginoscopic approach to diagnostic hysteroscopy to reduce the discomfort of the procedure, compared with the conventional approach. They did not place a vaginal speculum or tenaculum and, therefore, avoided placing local anesthetic into the cervix.3
A randomized controlled trial by Sagiv and colleagues found reduced pain during diagnostic hysteroscopy with vaginoscopy (VIDEO).4

In 2004, Bettocchi and colleagues reported nearly 5,000 operative hysteroscopic procedures performed with this technique (the “no-touch” technique) in an outpatient setting, demonstrating very high patient tolerance and a low degree of procedural pain. More than 90% of patients experienced little to no pain, except for those undergoing polypectomy when the polyps were larger than the diameter of the cervical os, as well as those who had anatomic abnormalities, with moderate discomfort reported by 33.2% and 12.7% of these women, respectively.5 These few patients may have benefited from anesthetic intervention for the procedure.
In a 2010 review of the literature on hysteroscopy without anesthesia, Cicinelli found that diagnostic hysteroscopy was more successful, with less patient discomfort, when smaller hysteroscopes were used (3.5 mm or smaller, including flexible lenses) and when the approach was vaginoscopic.1 Reduced pain with operative procedures was associated with a number of variables, including:
- increased surgeon experience
- smaller instrument size
- shorter duration of the procedure
- premenopausal status.
Variables associated with increased pain during operative procedures included:
- chronic pelvic pain
- menopausal status
- previous cesarean delivery
- significant anxiety.
In the review, Cicinelli noted that not all patients are likely to have a successful hysteroscopic procedure without the use of anesthesia or analgesia, regardless of the approach used.1
Only 1 randomized controlled trial explored the use of anesthesia (versus placebo) during operative hysteroscopy, and the authors found a benefit for preprocedural paracervical block using local anesthetic to reduce cervical pain.6
The success of diagnostic and operative hysteroscopic procedures with minimal and acceptable levels of patient discomfort in the office depends, therefore, on multiple factors. Procedural factors affecting the outcome of hysteroscopy include the size of the instrument used, the type and length of the procedure, the use of preprocedure anesthesia or analgesia, and a vaginoscopic approach. The skill of the surgeon also affects the hysteroscopic experience and outcome. In addition, patient variables such as menopausal status, anatomic distortion (eg, cervical stenosis), and anxiety may adversely affect the patient’s experience.
In summary, it is possible for the gynecologist to appropriately accommodate any given patient and clinical scenario, keeping in mind that many patients will require a customized approach for ultimate success. In this article, I review 3 recent studies on office hysteroscopy, focusing on the reduction of procedural pain and anxiety. Because of the protective effect of a high degree of surgeon experience, it is important that we offer adequate education in hysteroscopy during residency and postgraduate courses.
Placement of local anesthetic at multiple anatomic sites facilitates patient comfort during hysteroscopy
Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
In a 2010 review of randomized controlled trials of the use of local anesthesia versus placebo during hysteroscopy, data from several studies indicated a significant decrease in procedural pain when local anesthesia was given, while other studies found no difference.2 Most of the studies in that review evaluated a single site of anesthesia placement and focused on diagnostic hysteroscopy. The findings of that review, as well as the differential innervation of the uterine cervix and fundus (FIGURE), prompted Keyhan and Munro to evaluate the efficacy of multimodal local anesthetic for office diagnostic and operative hysteroscopy without the use of any systemic agents except for preprocedural cyclooxygenase (COX) inhibitors (TABLE 2). Accordingly, they placed local anesthetic at multiple anatomic sites to alleviate patient pain and improve procedural success in a spectrum of office-based hysteroscopic procedures.
Details of the trial
Procedures generally were performed using a continuous-flow sheath with an outside diameter of 5.5 mm and a 5 French operative channel for placement of operative instruments such as scissors, graspers, and sterilization microinserts. Normal saline or sterile water was used as the uterine distention medium, with gravity inflow assisted by pressure cuff, when necessary. Occasionally, a sheath system with an outside diameter of 6.5 mm was used, or an outside diameter of 9 mm for resectoscopic procedures using a bipolar radiofrequency resectoscope. When needed, cervical dilation was performed to accommodate the specific instrument used.
The impact of the multimodal, multisite anesthetic protocol was evaluated using contemporaneous patient reporting of numeric pain scores (worst pain experienced) that included anesthesia-related pain, procedure-related pain, and overall pain.
A total of 478 women underwent 535 procedures. A patient verbal response scale (range, 0–10) was used to assess the worst pain experienced. The overall mean (SD) procedure pain score was 3.7 (2.5). The mean score for patients undergoing diagnostic hysteroscopy was 3.2 (2.5), and it was 4.1 (2.5) for operative hysteroscopy (P<.001).
TABLE 3 shows the procedures performed under the anesthetic protocol. Pain associated with placement of anesthesia was similar for diagnostic and operative procedures (mean score, 2.7), but the mean overall pain scores for diagnostic procedures were about 1 unit less than for operative procedures, regardless of age or delivery history.
Complications were limited to 3 transient vasovagal episodes. Five procedures could not be completed because of intolerable pain or inability to access the uterine cavity. There was no difference in pain scores between menopausal and premeno-pausal women.
Malcolm G. Munro, MD, offers a protocol for pain relief during hysteroscopy
In this video, Malcolm G. Munro, MD, makes use of both topical and injectable lidocaine at 5 anatomic sites
Dr. Munro is Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA and Director of Gynecologic Services at Kaiser Permanente, Los Angeles Medical Center, in Los Angeles, California.
When placing anesthesia at multiple sites, allow time for onset of action
Keyhan and Munro demonstrated that successful completion of hysteroscopic procedures in the office environment can be achieved with acceptable levels of patient discomfort using a multimodal, multisite approach for preemptive placement of local anesthetic in the vagina, cervix, and endometrial cavity. They emphasize that the waiting time allotted for the onset of anesthesia is critical to the success of this approach. They also stress that no preprocedure oral sedative or narcotic is used with their approach. In addition, they note that the minimal discomfort experienced during placement of local anesthetic was overshadowed by general comfort during the wide spectrum of procedures performed.
What this EVIDENCE means for practice
The placement of preemptive local anesthesia at multiple anatomic sites facilitates diagnostic and operative hysteroscopy with an acceptable degree of patient comfort and successful completion of office procedures.
Music may reduce patient anxiety during hysteroscopy
Angioli R, De Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
Angioli and colleagues set out to address another factor that can impede patient comfort during office hysteroscopy—anxiety. Their randomized prospective trial is the only such trial evaluating the use of music to establish a calm and relaxing environment prior to office hysteroscopy for patients who are awake. Music supports an environment that “stimulates and maintains relaxation, well-being, and comfort and can be used as a self-management technique to reduce or control distress,” Angioli and colleagues write. The theory is that music distracts the patient by drawing her attention away from negative stimuli, thereby reducing pain, anxiety, and stress.
Details of the trial
A standardized visual analog scale (range, 0–10) was used to assess patient discomfort, and a State-Trait Anxiety Inventory (STAI; range, 20–80) also was given. Both tools were administered at baseline. The visual analog scale was measured again during the procedure, and the STAI was administered again after the procedure.
A hysteroscopic sheath with an outside diameter of 5 mm was used with a 5 French operative channel, and a vaginoscopic approach was used for each hysteroscopic procedure. A total of 372 women were enrolled and randomly allocated to either:
- music group (n = 185)
- no-music group (n = 187).
The surgical procedure was not completed in 15 patients (9 in the music group and 6 in the no-music group) because of stenosis of the cervix and/or excessive pain.
Women in the music group were allowed to select a playlist of classical, pop, jazz, or rock music that was played through a speaker system in the room. Of these patients, 50% preferred classical, 45% preferred pop, 5% chose jazz, and none selected rock music.
There were no statistically significant differences between the 2 groups in terms of preprocedure wait time, preprocedure scores on the visual analog scale or STAI, preprocedure vital signs, patient characteristics, type of procedure, or duration of the procedure. However, the music group had a lower visual analog score during the procedure and a lower postoperative STAI for diagnostic hysteroscopy than the no-music group did. The music group also had a statistically significant lower visual analog score for operative hysteroscopy than the no-music group did. In addition, the music group had a lower postoperative STAI score than the no-music group, but this difference was not statistically significant (TABLE 4).
Interestingly, in the music group, the STAI scores were lower after both diagnostic and operative hysteroscopy when classical music was selected rather than pop music.
Anxiety and pain are highly correlated
Angioli and colleagues found that patients who listened to music intraoperatively had a lower perception of pain and less anxiety. In addition, systolic blood pressure and heart rate were significantly lower in the music group than the no-music group, implying that patients who listened to music experienced less physical stress during the procedure.
Angioli and colleagues also noted that the level of anxiety and perception of pain were highly correlated. Pain is not an emotionally neutral experience but is almost always accompanied by distress. Investigators concluded that “anxiety can enhance painful sensations at all levels of the nervous system, from the peripheral receptors to the cortical level.”
What this EVIDENCE means for practice
Music is a useful complementary method to control patient anxiety and reduce the perception of pain during office hysteroscopy by creating a more relaxed and comfortable environment.
What are the risk factors for pain and discomfort during office hysteroscopy?
De Freitas FM, Sessa FV, Resende AD Jr, et al. Identifying predictors of unacceptable pain at office hysteroscopy. J Minim Invasive Gynecol. 2014;21(4):586–591.
De Freitas and colleagues conducted their prospective observational study to identify predictors of unacceptable pain during diagnostic office hysteroscopy (with or without directed or curette endometrial biopsy) and at the time of discharge. They hoped that any identifiable causes of unacceptable pain could be addressed individually in future patients undergoing office hysteroscopy to reduce their level of discomfort.
Details of the trial
A total of 558 procedures were evaluated. Hysteroscopists had varying levels of experience, with some having performed fewer than 50 procedures and others having performed more than 500.
A verbal response scale (range, 0–10) was used to assess pain at the end of each procedure and at the time of discharge. Investigators considered a score of 7 or more at the time of the procedure and a score of 4 or more at the time of discharge to be unacceptable.
A diagnostic, single-channel hysteroscope with an outside diameter of 3.5 mm was used with normal saline (at room temperature), along with a gravity system with pressure established to maintain intrauterine pressure at approximately 110 mm Hg. All hysteroscopic procedures were performed using a vaginoscopic approach, and biopsies were obtained as clinically indicated. Any patients who reported cramping at discharge (ie, a verbal response scale score of 4 or more) were offered an oral nonsteroidal anti-inflammatory drug.
Overall, the prevalence of unacceptable pain during office hysteroscopy was 32.3%. Experience of the hysteroscopist had a significant protective effect against pain. Longer procedures were significantly associated with unacceptable procedural pain.
The prevalence of unacceptable cramping at discharge was 28.6%. The risk of discomfort at discharge was significantly higher for women who reported dyspareunia or dysmenorrhea. Surgeon experience was significantly protective against unacceptable pain at discharge, and longer procedures were significantly associated with increased discomfort at discharge.
Dysmenorrhea and dyspareunia were significant predictors of pain at discharge
In this study, dysmenorrhea was a significant predictor of unacceptable pain at discharge, increasing the risk of unacceptable cramps by approximately threefold. Women who reported dyspareunia were nearly twice as likely to report unacceptable cramping at discharge.
Although a high level of expertise is not a prerequisite for office hysteroscopy, the skill and experience of the hysteroscopist, as well as shorter procedures, proved to be protective against procedural pain and discomfort at discharge but did not eliminate them altogether. Therefore, De Freitas and colleagues recommend that patients who can be identified as high-risk for procedural or discharge pain, such as women with dysmenorrhea or dyspareunia, should be offered preprocedure analgesia and/or anesthesia to reduce overall discomfort.
What this EVIDENCE means for practice
If a patient reports dysmenorrhea or dyspareunia preoperatively, she may benefit from preprocedure anesthesia or analgesia, or both, in an office setting.
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1. Cicinelli E. Hysteroscopy without anesthesia: review of recent literature. J Minim Invasive Gynecol. 2010;17(6):703–708.
2. Munro MG, Brooks PG. Use of local anesthesia for office diagnostic and operative hysteroscopy. J Minim Invasive Gynecol. 2010;17(6):709–718.
3. Bettocchi S, Selvaggi L. A vaginoscopic approach to reduce the pain of office hysteroscopy. J Am Assoc Gynecol Laparosc. 1997;4(2):255–258.
4. Sagiv R, Sadan O, Boaz M, et al. A new approach to office hysteroscopy compared with traditional hysteroscopy. A randomized controlled trial. Am J Obstet Gynecol. 2006;108(2):387–392.
5.Bettocchi S, Ceci O, Nappi L, et al. Operative office hysteroscopy without anesthesia: analysis of 4,863 cases performed with mechanical instruments. J Am Assoc Gynecol Laparosc. 2004;11(1):59–61.
6. Chudnoff S, Einstein M, Levie M. Paracervical block efficacy in office hysteroscopic sterilization. A randomized controlled trial. Obstet Gynecol. 2010;115(1):26–34.
7. Garcia AL. Stop performing dilation and curettage for the evaluation of abnormal uterine bleeding. OBG Manag. 2013;25(6):44–48.
8. Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
9. Angioli R, de Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
1. Cicinelli E. Hysteroscopy without anesthesia: review of recent literature. J Minim Invasive Gynecol. 2010;17(6):703–708.
2. Munro MG, Brooks PG. Use of local anesthesia for office diagnostic and operative hysteroscopy. J Minim Invasive Gynecol. 2010;17(6):709–718.
3. Bettocchi S, Selvaggi L. A vaginoscopic approach to reduce the pain of office hysteroscopy. J Am Assoc Gynecol Laparosc. 1997;4(2):255–258.
4. Sagiv R, Sadan O, Boaz M, et al. A new approach to office hysteroscopy compared with traditional hysteroscopy. A randomized controlled trial. Am J Obstet Gynecol. 2006;108(2):387–392.
5.Bettocchi S, Ceci O, Nappi L, et al. Operative office hysteroscopy without anesthesia: analysis of 4,863 cases performed with mechanical instruments. J Am Assoc Gynecol Laparosc. 2004;11(1):59–61.
6. Chudnoff S, Einstein M, Levie M. Paracervical block efficacy in office hysteroscopic sterilization. A randomized controlled trial. Obstet Gynecol. 2010;115(1):26–34.
7. Garcia AL. Stop performing dilation and curettage for the evaluation of abnormal uterine bleeding. OBG Manag. 2013;25(6):44–48.
8. Keyhan S, Munro MG. Office diagnostic and operative hysteroscopy using local anesthesia only: an analysis of patient reported pain and other procedural outcomes. J Minim Invasive Gynecol. 2014;21(5):791–798.
9. Angioli R, de Cicco Nardone C, Plotti F, et al. Use of music to reduce anxiety during office hysteroscopy: prospective randomized trial. J Minim Invasive Gynecol. 2014;21(3):454–459.
In this Article
— Innervation of the uterus
— Pain scores associated with specific hysteroscopic procedures