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Intra-amniotic sludge: Does its presence rule out cerclage for short cervix?

CASE: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).1 In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."2

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).3 Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.4

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.5 The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.6

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.4 In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.7 

 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.8 There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.9

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.10

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.11 Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.14

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

 

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.

References
  1. Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid "sludge" in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30(5):706-714.
  2. Romero R, Kusanovic JP, Espinoza J, et al. What is amniotic fluid "sludge"? Ultrasound Obstet Gynecol. 2007;30(5):793-798.
  3. Alfirevic Z, Stampalija T, Roberts D, Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;4:CD008991.
  4. Abbott D, To M, Shennan A. Cervical cerclage: a review of current evidence. Aust N Z J Obstet Gynaecol. 2012;52(3):220-223.
  5. Drassinower D, Poggi SH, Landy HJ, Gilo N, Benson JE, Ghidini A. Perioperative complications of history-indicated and ultrasound-indicated cervical cerclage. Am J Obstet Gynecol. 2011;205(1):53.e1-e5.
  6. Mays JK, Figueroa R, Shah J, Khakoo H, Kaminsky S, Tejani N. Amniocentesis for selection before rescue cerclage. Obstet Gynecol. 2000;95(5):652-655.
  7. Vaisbuch E, Romero R, Erez IO, et al. Clinical significance of early (<20 weeks) vs late (20-24 weeks) detection of sonographic short cervix in asymptomatic women in the mid-trimester. Ultrasound Obstet Gynecol. 2010;36(4):471-481.
  8. Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol. 2010;36(4):482-485.
  9. Ting YH, Lao TT, Wa Law LW, et al. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med. 2012;25(12):2693-2695.
  10. Yemini M, Borenstein R, Dreazen E, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-577.
  11. Berghella V, Figueroa D, Szychowski JM, et al; Vaginal Ultrasound Trial Consortium. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010;202(4):351.e1-e6.
  12. Rebarber A, Cleary-Goldman J, Istwan NB, et al. The use of 17 alpha-hydroxyprogesterone caproate (17P) in women with cervical cerclage. Am J Perinatol. 2008;25(5):271-275.
  13. Stetson B, Hibbard JU, Wilkins I, Leftwich H. Outcomes with cerclage alone compared with cerclage plus 17 &#945;-hydroxyprogesterone caproate. Obstet Gynecol. 2016;128(5):983-988.
  14. Iams JD. Identification of candidates for progesterone: why, who, how, and when? Obstet Gynecol. 2014;123(6):1317-1326.
Author and Disclosure Information

Dr. Tolcher is a Fellow in Maternal-Fetal Medicine at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women, Houston, Texas.

Dr. Vidaeff is Professor and Fellowship Program Director, Maternal-Fetal Medicine, at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women.

The authors report no financial relationships relevant to this article.

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Dr. Tolcher is a Fellow in Maternal-Fetal Medicine at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women, Houston, Texas.

Dr. Vidaeff is Professor and Fellowship Program Director, Maternal-Fetal Medicine, at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women.

The authors report no financial relationships relevant to this article.

Author and Disclosure Information

Dr. Tolcher is a Fellow in Maternal-Fetal Medicine at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women, Houston, Texas.

Dr. Vidaeff is Professor and Fellowship Program Director, Maternal-Fetal Medicine, at Baylor College of Medicine and Texas Children's Hospital, Pavilion for Women.

The authors report no financial relationships relevant to this article.

CASE: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).1 In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."2

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).3 Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.4

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.5 The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.6

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.4 In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.7 

 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.8 There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.9

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.10

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.11 Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.14

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

 

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: Woman with short cervix, intra-amniotic sludge, and prior preterm delivery

An asymptomatic 32-year-old woman with a prior preterm delivery, presently pregnant with a singleton at 17 weeks of gestation, underwent transvaginal ultrasonography and was found to have a cervical length of 22 mm and dense intra-amniotic sludge. She received one dose of 17α-hydroxyprogesterone caproate (17P) at 16 weeks of gestation. What are your next steps in management?

Intra-amniotic sludge is a conundrum 

Intra-amniotic sludge is a sonographic finding of free-floating, hyperechoic, particulate matter in the amniotic fluid close to the internal os. The precise nature of this material varies, and it may include blood, meconium, or vernix and may signal inflammation or infection. In a retrospective case-control study, 27% of asymptomatic women with sludge and a short cervix had positive amniotic fluid cultures, and 27% had evidence of inflammation in the amniotic fluid (>50 white blood cells/mm3).1 In a separate report, the authors proposed that "the detection of amniotic fluid 'sludge' represents a sign that microbial invasion of the amniotic cavity and an inflammatory process are in progress."2

Benefit of cerclage in high-risk women. Several systematic reviews have highlighted the benefit of cerclage for women with a singleton pregnancy, short cervix, and previous preterm birth or second-trimester loss (ultrasound-indicated cerclage for high-risk women).3 Cerclage is presumed to work by providing some degree of structural support and by maintaining a barrier to protect the fetal membranes against exposure to ascending pathogens.4

Since dense intra-amniotic sludge may represent chronic intra-amniotic infection, can cerclage still be expected to be beneficial when microbiologic invasion of the amniotic cavity already has occurred? Furthermore, intra-amniotic infection has been cited as a possible complication of ultrasound-indicated cerclage, with a rate of 10%.5 The traditional view is that the presence of subclinical intra-amniotic infection may further increase this risk and therefore should be considered a contraindication to cerclage.6

Evaluating the patient for cerclage placement

The patient history and physical examination should focus on the signs and symptoms of labor, vaginal bleeding, amniotic membrane rupture, and intra-amniotic infection. Particular attention should be paid to maternal temperature, pulse, and the presence of uterine tenderness or foul-smelling vaginal discharge. A sterile speculum examination followed by digital examination would complement the ultrasonography evaluation in assessing cervical dilation and effacement. The ultrasonography evaluation should be completed to confirm a viable pregnancy with accurate dating and the absence of detectable fetal anomalies.

Currently, evidence is insufficient for recommending routine amniocentesis to exclude intra-amniotic infection in an asymptomatic woman prior to ultrasound-indicated cerclage, even in the presence of intra-amniotic sludge, as there are no data demonstrating improved outcomes.4 In addition, intra-amniotic sludge has been associated with intra-amniotic infection and/or inflammation in the form of microbial biofilms, which may prevent detection of infection by routine culture techniques.7 

 

Related Article:
Universal cervical length screening–saving babies lives

Study results offer limited guidance

Data are limited on the clinical implications of intra-amniotic sludge in women with cervical cerclage. In a retrospective cohort of 177 patients with cerclage, 60 had evidence of sludge and 46 of those with sludge underwent ultrasound-indicated cerclage.8 There were no significant differences in the mean gestational age at delivery, neonatal outcomes, rate of preterm delivery, preterm premature rupture of membranes, or intra-amniotic infection between women with or without intra-amniotic sludge. A subanalysis was performed comparing women with sludge detected before or after cerclage and, again, no difference was found in measured outcomes.

Similarly, in a small (N = 20) retrospective review of the Arabin pessary used as a noninvasive intervention for short cervix, the presence of intra-amniotic sludge in 5 cases did not appear to impact outcomes.9

Case patient: How would you manage her care?

Based on her obstetric history and ultrasonography findings, the patient described in the case vignette is at high risk for preterm delivery. The presence of both intra-amniotic sludge and short cervix is associated with an increased risk for spontaneous preterm delivery. After evaluating for clinical intra-amniotic infection and performing a work-up for other contraindications to cerclage placement, cerclage placement may be offered--even in the presence of intra-amniotic sludge.

The next practical question is whether 17P, already started, should be continued after cerclage placement. From the literature on 17P, it is unclear whether progesterone provides additional benefit. One randomized, placebo-controlled study in women with at least 2 preterm deliveries or mid-trimester losses and cerclage in place showed that the 17P-treated women had a significant reduction in preterm delivery compared with the control group, from 37.8% to 16.1%.10

By contrast, in a secondary analysis of a randomized trial evaluating cerclage in high-risk women with short cervix in the current pregnancy, addition of 17P to cerclage was not beneficial.11 Results of 2 retrospective cohort studies showed the same lack of difference on preterm delivery rates with the addition of 17P.12,13

Accepting that the interpretation of these data is challenging, in our practice we would choose to continue the progesterone supplementation, siding with other recently expressed expert opinions.14

The bottom line

While clinical intra-amniotic infection is a contraindication to cerclage, there is no evidence to support withholding cerclage from eligible women due to the presence of intra-amniotic fluid sludge alone.

 

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.

References
  1. Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid "sludge" in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30(5):706-714.
  2. Romero R, Kusanovic JP, Espinoza J, et al. What is amniotic fluid "sludge"? Ultrasound Obstet Gynecol. 2007;30(5):793-798.
  3. Alfirevic Z, Stampalija T, Roberts D, Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;4:CD008991.
  4. Abbott D, To M, Shennan A. Cervical cerclage: a review of current evidence. Aust N Z J Obstet Gynaecol. 2012;52(3):220-223.
  5. Drassinower D, Poggi SH, Landy HJ, Gilo N, Benson JE, Ghidini A. Perioperative complications of history-indicated and ultrasound-indicated cervical cerclage. Am J Obstet Gynecol. 2011;205(1):53.e1-e5.
  6. Mays JK, Figueroa R, Shah J, Khakoo H, Kaminsky S, Tejani N. Amniocentesis for selection before rescue cerclage. Obstet Gynecol. 2000;95(5):652-655.
  7. Vaisbuch E, Romero R, Erez IO, et al. Clinical significance of early (<20 weeks) vs late (20-24 weeks) detection of sonographic short cervix in asymptomatic women in the mid-trimester. Ultrasound Obstet Gynecol. 2010;36(4):471-481.
  8. Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol. 2010;36(4):482-485.
  9. Ting YH, Lao TT, Wa Law LW, et al. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med. 2012;25(12):2693-2695.
  10. Yemini M, Borenstein R, Dreazen E, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-577.
  11. Berghella V, Figueroa D, Szychowski JM, et al; Vaginal Ultrasound Trial Consortium. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010;202(4):351.e1-e6.
  12. Rebarber A, Cleary-Goldman J, Istwan NB, et al. The use of 17 alpha-hydroxyprogesterone caproate (17P) in women with cervical cerclage. Am J Perinatol. 2008;25(5):271-275.
  13. Stetson B, Hibbard JU, Wilkins I, Leftwich H. Outcomes with cerclage alone compared with cerclage plus 17 &#945;-hydroxyprogesterone caproate. Obstet Gynecol. 2016;128(5):983-988.
  14. Iams JD. Identification of candidates for progesterone: why, who, how, and when? Obstet Gynecol. 2014;123(6):1317-1326.
References
  1. Kusanovic JP, Espinoza J, Romero R, et al. Clinical significance of the presence of amniotic fluid "sludge" in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30(5):706-714.
  2. Romero R, Kusanovic JP, Espinoza J, et al. What is amniotic fluid "sludge"? Ultrasound Obstet Gynecol. 2007;30(5):793-798.
  3. Alfirevic Z, Stampalija T, Roberts D, Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;4:CD008991.
  4. Abbott D, To M, Shennan A. Cervical cerclage: a review of current evidence. Aust N Z J Obstet Gynaecol. 2012;52(3):220-223.
  5. Drassinower D, Poggi SH, Landy HJ, Gilo N, Benson JE, Ghidini A. Perioperative complications of history-indicated and ultrasound-indicated cervical cerclage. Am J Obstet Gynecol. 2011;205(1):53.e1-e5.
  6. Mays JK, Figueroa R, Shah J, Khakoo H, Kaminsky S, Tejani N. Amniocentesis for selection before rescue cerclage. Obstet Gynecol. 2000;95(5):652-655.
  7. Vaisbuch E, Romero R, Erez IO, et al. Clinical significance of early (<20 weeks) vs late (20-24 weeks) detection of sonographic short cervix in asymptomatic women in the mid-trimester. Ultrasound Obstet Gynecol. 2010;36(4):471-481.
  8. Gorski LA, Huang WH, Iriye BK, Hancock J. Clinical implication of intra-amniotic sludge on ultrasound in patients with cervical cerclage. Ultrasound Obstet Gynecol. 2010;36(4):482-485.
  9. Ting YH, Lao TT, Wa Law LW, et al. Arabin cerclage pessary in the management of cervical insufficiency. J Matern Fetal Neonatal Med. 2012;25(12):2693-2695.
  10. Yemini M, Borenstein R, Dreazen E, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151(5):574-577.
  11. Berghella V, Figueroa D, Szychowski JM, et al; Vaginal Ultrasound Trial Consortium. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010;202(4):351.e1-e6.
  12. Rebarber A, Cleary-Goldman J, Istwan NB, et al. The use of 17 alpha-hydroxyprogesterone caproate (17P) in women with cervical cerclage. Am J Perinatol. 2008;25(5):271-275.
  13. Stetson B, Hibbard JU, Wilkins I, Leftwich H. Outcomes with cerclage alone compared with cerclage plus 17 &#945;-hydroxyprogesterone caproate. Obstet Gynecol. 2016;128(5):983-988.
  14. Iams JD. Identification of candidates for progesterone: why, who, how, and when? Obstet Gynecol. 2014;123(6):1317-1326.
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