How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●

How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●

How should I be approaching cervical cancer screening: with primary human papillomavirus (HPV) testing, or cotesting? We get this question all the time from clinicians. Although they have heard of the latest cervical cancer screening guidelines for stand-alone “primary” HPV testing, they are still ordering cervical cytology (Papanicolaou, or Pap, test) for women aged 21 to 29 years and cotesting (cervical cytology with HPV testing) for women with a cervix aged 30 and older.

Changes in cervical cancer testing guidance

Cervical cancer occurs in more than 13,000 women in the United States annually.¹ High-risk types of HPV—the known cause of cervical cancer—also cause a large majority of cancers of the anus, vagina, vulva, and oropharynx.²

Cervical cancer screening programs in the United States have markedly decreased the incidence of and mortality from cervical cancer since introduction of the Pap smear in the 1950s. In 2000, HPV testing was approved by the US Food and Drug Administration (FDA) as a reflex test to a Pap smear result of atypical squamous cells of undetermined significance (ASC-US). HPV testing was then approved for use with cytology as a cotest in 2003 and subsequently as a primary stand-alone test in 2014.

Recently, the American Cancer Society (ACS) released new cervical screening guidelines that depart from prior guidelines.³ They recommend not to screen 21- to 24-year-olds and to start screening at age 25 until age 65 with the preferred strategy of primary HPV testing every 5 years, using an FDA-approved HPV test. Alternative screening strategies are cytology (Pap) every 3 years or cotesting every 5 years.

The 2018 US Preventive Services Task Force (USPSTF) guidelines differ from the ACS guidelines. The USPSTF recommends cytology every 3 years as the preferred method for women with a cervix who are aged 21 to 29 years and, for women with a cervix who are aged 30 to 65 years, the option for cytology every 3 years, primary HPV testing every 5 years, or cotesting every 5 years (TABLE).⁴

Why the reluctance to switch to HPV testing?

Despite FDA approval in 2014 for primary HPV testing and concurrent professional society guidance to use this testing strategy in women with a cervix who are aged 25 years and older, few practices in the United States have switched over to primary HPV testing for cervical cancer screening.^5,6 Several reasons underlie this inertia:

• Many practices currently use HPV tests that are not FDA approved for primary HPV testing.
• Until recently, national screening guidelines did not recommend primary HPV testing as the preferred testing strategy.
• Long-established guidance on the importance of regular cervical cytology screening promoted by the ACS and others (which especially impacts women with a cervix older than age 50 who guide their younger daughters) will rely on significant re-education to move away from the established “Pap smear” cultural icon to a new approach.
• Last but not least, companies that manufacture HPV tests and laboratories integrated to offer such tests not yet approved for primary screening are promoting reliance on the prior proven cotest strategy. They have lobbied to preserve cotesting as a primary test, with some laboratory database studies showing gaps in detection with HPV test screening alone.^7-9

Currently, the FDA-approved HPV tests for primary HPV screening include the Cobas HPV test (Roche) and the BD Onclarity HPV assay (Becton, Dickinson and Company). Both are DNA tests for 14 high-risk types of HPV that include genotyping for HPV 16 and 18.

Continue to: Follow the evidence...

Several trials in Europe and Canada provide supporting evidence for primary HPV testing, and many European countries have moved to primary HPV testing as their preferred screening method.^10,11 The new ACS guidelines put us more in sync with the rest of the world, where HPV testing is the dominant strategy.

It is true that doing additional tests will find more disease; cotesting has been shown to very minimally increase detection of cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) compared with HPV testing alone, but it incurs many more costs and procedures.¹² The vast majority of cervical cancer is HPV positive, and cytology still can be used as a triage to primary HPV screening until tests with better sensitivity and/or specificity (such as dual stain and methylation) can be employed to reduce unnecessary “false-positive” driven procedures.

As mentioned, many strong forces are trying to keep cotesting as the preferred strategy. It is important for clinicians to recognize the corporate investment into screening platforms, relationships, and products that underlie some of these efforts so as not to be unfairly influenced by their lobbying. Data from well-conducted, high-quality studies should be the evidence on which one bases a cervical cancer screening strategy.

Innovation catalyzes change

We acknowledge that it is difficult to give up something you have been doing for decades, so there is natural resistance by both patients and clinicians to move the Pap smear into a secondary role. But the data support primary HPV testing as the best screening option from a public health perspective.

At some point, hopefully soon, primary HPV testing will receive approval for self-sampling; this has the potential to reach patients in rural or remote locations who may otherwise not get screened for cervical cancer.¹³

The 2019 risk-based management guidelines from the ASCCP (American Society for Colposcopy and Cervical Pathology) also incorporate the use of HPV-based screening and surveillance after abnormal tests or colposcopy. Therefore, switching to primary HPV screening will not impact your ability to follow patients appropriately based on clinical guidelines.

Our advice to clinicians is to switch to primary HPV screening now if possible. If that is not feasible, continue your current strategy until you can make the change. And, of course, we recommend that you implement an HPV vaccination program in your practice to maximize primary prevention of HPV-related cancers. ●

Uterine leiomyomata (fibroids) are the most common pelvic tumor of women. When women are planning to conceive, and their fibroid(s) are clinically significant, causing abnormal uterine bleeding or bulk symptoms, it is often optimal to remove the uterine tumor(s) before conception. Advances in minimally invasive surgery offer women the option of laparoscopic or robot-assisted myomectomy with a low rate of operative complications, including excessive blood loss and hysterectomy, and a low rate of postoperative complications, including major pelvic adhesions and uterine rupture during subsequent pregnancy.^1-3 However, many women become pregnant when they have clinically significant fibroids, and at least one-third of these women will have a cesarean birth.

Important clinical issues are the relative benefits and risks of performing a myomectomy at the time of the cesarean birth, so called cesarean myomectomy. Cesarean myomectomy offers carefully selected women the opportunity to have a cesarean birth and myomectomy in one operation, thereby avoiding a second major operation. Over the past 6 decades, most experts in the United States and the United Kingdom have strongly recommended against myomectomy at the time of cesarean delivery because of the risk of excessive blood loss and hysterectomy. Recently, expert opinion has shifted, especially in continental Europe and Asia, and cesarean myomectomy is now viewed as an acceptable surgical option in a limited number of clinical situations, including removal of pedunculated fibroids, excision of large solitary subserosal fibroids, and to achieve optimal management of the hysterotomy incision.

Decades of expert guidance: Avoid cesarean myomectomy at all costs

Dr. K.S.J. Olah succinctly captured the standard teaching that cesarean myomectomy should be avoided in this personal vignette:

Many years ago as a trainee I removed a subserosal fibroid during a cesarean section that was hanging by a thin stalk on the back of the uterus. The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden. It has always been considered foolish to consider removing fibroids at cesarean section, mostly because of the associated morbidity and the risk of haemorrhage requiring hysterectomy.⁴

Dr. Olah quoted guidance from Shaw’s Textbook of Operative Gynaecology,⁵ “It should be stressed that myomectomy in pregnancy should be avoided at all costs, including at caesarean section.” However, large case series published over the past 10 years report that, in limited clinical situations, cesarean myomectomy is a viable surgical option, where benefit may outweigh risk.^6-14 The current literature has many weaknesses, including failure to specifically identify the indication for the cesarean myomectomy and lack of controlled prospective clinical trials. In almost all cases, cesarean myomectomy is performed after delivery of the fetus and placenta.

Continue to: The pedunculated, FIGO type 7 fibroid...

The International Federation of Gynecology and Obstetrics (FIGO) leiomyoma classification system identifies subserosal pedunculated fibroids as type 7 (FIGURE).¹⁵ Pedunculated fibroids are attached to the uterus by a stalk that is ≤10% of the mean of the 3 diameters of the fibroid. When a clinically significant pedunculated fibroid, causing bulk symptoms, is encountered at cesarean birth, I recommend that it be removed. This will save many patients a second major operation to perform a myomectomy. The surgical risk of removing a pedunculated is low.

The solitary FIGO type 6 fibroid

Type 6 fibroids are subserosal fibroids with less than 50% of their mass being subserosal. The type 6 fibroid is relatively easy to enucleate from the uterus. Following removal of a type 6 fibroid, closure of the serosal defect is relatively straightforward. In carefully selected cases, if the type 6 fibroid is causing bulk symptoms, cesarean myomectomy may be indicated with a low risk of operative complications.

The FIGO type 2-5 fibroid

The type 2-5 fibroid is a transmural fibroid with significant mass abutting both the endometrial cavity and serosal surface. Excision of a type 2-5 fibroid is likely to result in a large transmyometrial defect that will be more difficult to close and could be associated with greater blood loss. Although data are limited, I would recommend against cesarean myomectomy for type 2-5 fibroids in most clinical situations.

Myomectomy to achieve optimal management of the cesarean hysterotomy incision

Many surgeons performing a cesarean birth for a woman with clinically significant fibroids will plan the hysterotomy incision to avoid the fibroids. However, following delivery and contraction of the uterus, proper closure of the hysterotomy incision may be very difficult without removing a fibroid that is abutting the hysterotomy incision. Surgeons have reported performing myomectomy on lower uterine segment fibroids before making the hysterotomy incision in order to facilitate the hysterotomy incision and closure.¹⁶ Myomectomy prior to delivery of the newborn must be associated with additional risks to the fetus. I would prefer to identify an optimal site to perform a hysterotomy, deliver the newborn and placenta, and then consider myomectomy.

Complications associated with cesarean myomectomy

The evidence concerning the complications of cesarean birth plus myomectomy compared with cesarean birth alone in women with fibroids is limited to case series. There are no reported controlled clinical trials to guide practice. The largest single case series reported on 1,242 women with fibroids who had a cesarean birth plus myomectomy compared with 3 control groups, including 200 women without fibroids who had a cesarean birth, 145 women with fibroids who had a cesarean birth and no myomectomy, and 51 women with fibroids who had a cesarean hysterectomy. The investigators reported no significant differences in preoperative to postoperative hemoglobin change, incidence of postoperative fever, or length of hospital stay among the 4 groups.⁸ The authors concluded that myomectomy during cesarean birth was a safe and effective procedure.

Continue to: A systematic review and meta-analysis reported...

A systematic review and meta-analysis reported on the results of 17 studies which included 4,702 women who had a cesarean myomectomy and 1,843 women with cesarean birth without myomectomy.¹⁷ The authors of the meta-analysis noted that most reported case series had excluded women with a high risk of bleeding, including women with placenta previa, placenta accreta, coagulation disorders, and a history of multiple myomectomy operations. The investigators reported that, compared with the control women, the women undergoing cesarean myomectomy had a statistically significant but clinically insignificant decrease in mean hemoglobin concentration (-0.27 g/dL), a significant increase in mean operative time (+15 minutes) and a significant increase in the length of hospital stay (+0.36 days). There was an increase in the need for blood transfusion (risk ratio, 1.45; 95% confidence interval, 1.05–1.99), but only 3% of women undergoing cesarean myomectomy received a blood transfusion. There was no significant difference between the two groups in the incidence of postoperative fever. The authors concluded that cesarean myomectomy is a safe procedure when performed by experienced surgeons with appropriate hemostatic techniques.

Techniques to reduce blood loss at the time of cesarean myomectomy

A detailed review of all the available techniques to reduce blood loss at the time of cesarean myomectomy is beyond the scope of this editorial. All gynecologists know that control of uterine blood flow through the uterine artery, infundibulopelvic vessels and internal iliac artery can help to reduce bleeding at the time of myomectomy. Tourniquets, vascular clamps, and artery ligation all have been reported to be useful at the time of cesarean myomectomy. In addition, intravenous infusion of oxytocin and tranexamic acid is often used at the time of cesarean myomectomy. Direct injection of uterotonics, including carbetocin, oxytocin, and vasopressin, into the uterus also has been reported. Cell saver blood salvage technology has been utilized in a limited number of cases of cesarean myomectomy.^8,18,19

Medicine is not a static field

Discoveries and new data help guide advances in medical practice. After 6 decades of strict adherence to the advice that myomectomy in pregnancy should be avoided at all costs, including at caesarean delivery, new data indicate that in carefully selected cases cesarean myomectomy is an acceptable operation. ●

Uterine leiomyomata (fibroids) are the most common pelvic tumor of women. When women are planning to conceive, and their fibroid(s) are clinically significant, causing abnormal uterine bleeding or bulk symptoms, it is often optimal to remove the uterine tumor(s) before conception. Advances in minimally invasive surgery offer women the option of laparoscopic or robot-assisted myomectomy with a low rate of operative complications, including excessive blood loss and hysterectomy, and a low rate of postoperative complications, including major pelvic adhesions and uterine rupture during subsequent pregnancy.^1-3 However, many women become pregnant when they have clinically significant fibroids, and at least one-third of these women will have a cesarean birth.

Important clinical issues are the relative benefits and risks of performing a myomectomy at the time of the cesarean birth, so called cesarean myomectomy. Cesarean myomectomy offers carefully selected women the opportunity to have a cesarean birth and myomectomy in one operation, thereby avoiding a second major operation. Over the past 6 decades, most experts in the United States and the United Kingdom have strongly recommended against myomectomy at the time of cesarean delivery because of the risk of excessive blood loss and hysterectomy. Recently, expert opinion has shifted, especially in continental Europe and Asia, and cesarean myomectomy is now viewed as an acceptable surgical option in a limited number of clinical situations, including removal of pedunculated fibroids, excision of large solitary subserosal fibroids, and to achieve optimal management of the hysterotomy incision.

Decades of expert guidance: Avoid cesarean myomectomy at all costs

Dr. K.S.J. Olah succinctly captured the standard teaching that cesarean myomectomy should be avoided in this personal vignette:

Many years ago as a trainee I removed a subserosal fibroid during a cesarean section that was hanging by a thin stalk on the back of the uterus. The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden. It has always been considered foolish to consider removing fibroids at cesarean section, mostly because of the associated morbidity and the risk of haemorrhage requiring hysterectomy.⁴

Dr. Olah quoted guidance from Shaw’s Textbook of Operative Gynaecology,⁵ “It should be stressed that myomectomy in pregnancy should be avoided at all costs, including at caesarean section.” However, large case series published over the past 10 years report that, in limited clinical situations, cesarean myomectomy is a viable surgical option, where benefit may outweigh risk.^6-14 The current literature has many weaknesses, including failure to specifically identify the indication for the cesarean myomectomy and lack of controlled prospective clinical trials. In almost all cases, cesarean myomectomy is performed after delivery of the fetus and placenta.

Continue to: The pedunculated, FIGO type 7 fibroid...

The International Federation of Gynecology and Obstetrics (FIGO) leiomyoma classification system identifies subserosal pedunculated fibroids as type 7 (FIGURE).¹⁵ Pedunculated fibroids are attached to the uterus by a stalk that is ≤10% of the mean of the 3 diameters of the fibroid. When a clinically significant pedunculated fibroid, causing bulk symptoms, is encountered at cesarean birth, I recommend that it be removed. This will save many patients a second major operation to perform a myomectomy. The surgical risk of removing a pedunculated is low.

The solitary FIGO type 6 fibroid

Type 6 fibroids are subserosal fibroids with less than 50% of their mass being subserosal. The type 6 fibroid is relatively easy to enucleate from the uterus. Following removal of a type 6 fibroid, closure of the serosal defect is relatively straightforward. In carefully selected cases, if the type 6 fibroid is causing bulk symptoms, cesarean myomectomy may be indicated with a low risk of operative complications.

The FIGO type 2-5 fibroid

The type 2-5 fibroid is a transmural fibroid with significant mass abutting both the endometrial cavity and serosal surface. Excision of a type 2-5 fibroid is likely to result in a large transmyometrial defect that will be more difficult to close and could be associated with greater blood loss. Although data are limited, I would recommend against cesarean myomectomy for type 2-5 fibroids in most clinical situations.

Myomectomy to achieve optimal management of the cesarean hysterotomy incision

Many surgeons performing a cesarean birth for a woman with clinically significant fibroids will plan the hysterotomy incision to avoid the fibroids. However, following delivery and contraction of the uterus, proper closure of the hysterotomy incision may be very difficult without removing a fibroid that is abutting the hysterotomy incision. Surgeons have reported performing myomectomy on lower uterine segment fibroids before making the hysterotomy incision in order to facilitate the hysterotomy incision and closure.¹⁶ Myomectomy prior to delivery of the newborn must be associated with additional risks to the fetus. I would prefer to identify an optimal site to perform a hysterotomy, deliver the newborn and placenta, and then consider myomectomy.

Complications associated with cesarean myomectomy

The evidence concerning the complications of cesarean birth plus myomectomy compared with cesarean birth alone in women with fibroids is limited to case series. There are no reported controlled clinical trials to guide practice. The largest single case series reported on 1,242 women with fibroids who had a cesarean birth plus myomectomy compared with 3 control groups, including 200 women without fibroids who had a cesarean birth, 145 women with fibroids who had a cesarean birth and no myomectomy, and 51 women with fibroids who had a cesarean hysterectomy. The investigators reported no significant differences in preoperative to postoperative hemoglobin change, incidence of postoperative fever, or length of hospital stay among the 4 groups.⁸ The authors concluded that myomectomy during cesarean birth was a safe and effective procedure.

Continue to: A systematic review and meta-analysis reported...

A systematic review and meta-analysis reported on the results of 17 studies which included 4,702 women who had a cesarean myomectomy and 1,843 women with cesarean birth without myomectomy.¹⁷ The authors of the meta-analysis noted that most reported case series had excluded women with a high risk of bleeding, including women with placenta previa, placenta accreta, coagulation disorders, and a history of multiple myomectomy operations. The investigators reported that, compared with the control women, the women undergoing cesarean myomectomy had a statistically significant but clinically insignificant decrease in mean hemoglobin concentration (-0.27 g/dL), a significant increase in mean operative time (+15 minutes) and a significant increase in the length of hospital stay (+0.36 days). There was an increase in the need for blood transfusion (risk ratio, 1.45; 95% confidence interval, 1.05–1.99), but only 3% of women undergoing cesarean myomectomy received a blood transfusion. There was no significant difference between the two groups in the incidence of postoperative fever. The authors concluded that cesarean myomectomy is a safe procedure when performed by experienced surgeons with appropriate hemostatic techniques.

Techniques to reduce blood loss at the time of cesarean myomectomy

A detailed review of all the available techniques to reduce blood loss at the time of cesarean myomectomy is beyond the scope of this editorial. All gynecologists know that control of uterine blood flow through the uterine artery, infundibulopelvic vessels and internal iliac artery can help to reduce bleeding at the time of myomectomy. Tourniquets, vascular clamps, and artery ligation all have been reported to be useful at the time of cesarean myomectomy. In addition, intravenous infusion of oxytocin and tranexamic acid is often used at the time of cesarean myomectomy. Direct injection of uterotonics, including carbetocin, oxytocin, and vasopressin, into the uterus also has been reported. Cell saver blood salvage technology has been utilized in a limited number of cases of cesarean myomectomy.^8,18,19

Medicine is not a static field

Discoveries and new data help guide advances in medical practice. After 6 decades of strict adherence to the advice that myomectomy in pregnancy should be avoided at all costs, including at caesarean delivery, new data indicate that in carefully selected cases cesarean myomectomy is an acceptable operation. ●

Uterine leiomyomata (fibroids) are the most common pelvic tumor of women. When women are planning to conceive, and their fibroid(s) are clinically significant, causing abnormal uterine bleeding or bulk symptoms, it is often optimal to remove the uterine tumor(s) before conception. Advances in minimally invasive surgery offer women the option of laparoscopic or robot-assisted myomectomy with a low rate of operative complications, including excessive blood loss and hysterectomy, and a low rate of postoperative complications, including major pelvic adhesions and uterine rupture during subsequent pregnancy.^1-3 However, many women become pregnant when they have clinically significant fibroids, and at least one-third of these women will have a cesarean birth.

Important clinical issues are the relative benefits and risks of performing a myomectomy at the time of the cesarean birth, so called cesarean myomectomy. Cesarean myomectomy offers carefully selected women the opportunity to have a cesarean birth and myomectomy in one operation, thereby avoiding a second major operation. Over the past 6 decades, most experts in the United States and the United Kingdom have strongly recommended against myomectomy at the time of cesarean delivery because of the risk of excessive blood loss and hysterectomy. Recently, expert opinion has shifted, especially in continental Europe and Asia, and cesarean myomectomy is now viewed as an acceptable surgical option in a limited number of clinical situations, including removal of pedunculated fibroids, excision of large solitary subserosal fibroids, and to achieve optimal management of the hysterotomy incision.

Decades of expert guidance: Avoid cesarean myomectomy at all costs

Dr. K.S.J. Olah succinctly captured the standard teaching that cesarean myomectomy should be avoided in this personal vignette:

Many years ago as a trainee I removed a subserosal fibroid during a cesarean section that was hanging by a thin stalk on the back of the uterus. The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden. It has always been considered foolish to consider removing fibroids at cesarean section, mostly because of the associated morbidity and the risk of haemorrhage requiring hysterectomy.⁴

Dr. Olah quoted guidance from Shaw’s Textbook of Operative Gynaecology,⁵ “It should be stressed that myomectomy in pregnancy should be avoided at all costs, including at caesarean section.” However, large case series published over the past 10 years report that, in limited clinical situations, cesarean myomectomy is a viable surgical option, where benefit may outweigh risk.^6-14 The current literature has many weaknesses, including failure to specifically identify the indication for the cesarean myomectomy and lack of controlled prospective clinical trials. In almost all cases, cesarean myomectomy is performed after delivery of the fetus and placenta.

Continue to: The pedunculated, FIGO type 7 fibroid...

The International Federation of Gynecology and Obstetrics (FIGO) leiomyoma classification system identifies subserosal pedunculated fibroids as type 7 (FIGURE).¹⁵ Pedunculated fibroids are attached to the uterus by a stalk that is ≤10% of the mean of the 3 diameters of the fibroid. When a clinically significant pedunculated fibroid, causing bulk symptoms, is encountered at cesarean birth, I recommend that it be removed. This will save many patients a second major operation to perform a myomectomy. The surgical risk of removing a pedunculated is low.

The solitary FIGO type 6 fibroid

Type 6 fibroids are subserosal fibroids with less than 50% of their mass being subserosal. The type 6 fibroid is relatively easy to enucleate from the uterus. Following removal of a type 6 fibroid, closure of the serosal defect is relatively straightforward. In carefully selected cases, if the type 6 fibroid is causing bulk symptoms, cesarean myomectomy may be indicated with a low risk of operative complications.

The FIGO type 2-5 fibroid

The type 2-5 fibroid is a transmural fibroid with significant mass abutting both the endometrial cavity and serosal surface. Excision of a type 2-5 fibroid is likely to result in a large transmyometrial defect that will be more difficult to close and could be associated with greater blood loss. Although data are limited, I would recommend against cesarean myomectomy for type 2-5 fibroids in most clinical situations.

Myomectomy to achieve optimal management of the cesarean hysterotomy incision

Many surgeons performing a cesarean birth for a woman with clinically significant fibroids will plan the hysterotomy incision to avoid the fibroids. However, following delivery and contraction of the uterus, proper closure of the hysterotomy incision may be very difficult without removing a fibroid that is abutting the hysterotomy incision. Surgeons have reported performing myomectomy on lower uterine segment fibroids before making the hysterotomy incision in order to facilitate the hysterotomy incision and closure.¹⁶ Myomectomy prior to delivery of the newborn must be associated with additional risks to the fetus. I would prefer to identify an optimal site to perform a hysterotomy, deliver the newborn and placenta, and then consider myomectomy.

Complications associated with cesarean myomectomy

The evidence concerning the complications of cesarean birth plus myomectomy compared with cesarean birth alone in women with fibroids is limited to case series. There are no reported controlled clinical trials to guide practice. The largest single case series reported on 1,242 women with fibroids who had a cesarean birth plus myomectomy compared with 3 control groups, including 200 women without fibroids who had a cesarean birth, 145 women with fibroids who had a cesarean birth and no myomectomy, and 51 women with fibroids who had a cesarean hysterectomy. The investigators reported no significant differences in preoperative to postoperative hemoglobin change, incidence of postoperative fever, or length of hospital stay among the 4 groups.⁸ The authors concluded that myomectomy during cesarean birth was a safe and effective procedure.

Continue to: A systematic review and meta-analysis reported...

A systematic review and meta-analysis reported on the results of 17 studies which included 4,702 women who had a cesarean myomectomy and 1,843 women with cesarean birth without myomectomy.¹⁷ The authors of the meta-analysis noted that most reported case series had excluded women with a high risk of bleeding, including women with placenta previa, placenta accreta, coagulation disorders, and a history of multiple myomectomy operations. The investigators reported that, compared with the control women, the women undergoing cesarean myomectomy had a statistically significant but clinically insignificant decrease in mean hemoglobin concentration (-0.27 g/dL), a significant increase in mean operative time (+15 minutes) and a significant increase in the length of hospital stay (+0.36 days). There was an increase in the need for blood transfusion (risk ratio, 1.45; 95% confidence interval, 1.05–1.99), but only 3% of women undergoing cesarean myomectomy received a blood transfusion. There was no significant difference between the two groups in the incidence of postoperative fever. The authors concluded that cesarean myomectomy is a safe procedure when performed by experienced surgeons with appropriate hemostatic techniques.

Techniques to reduce blood loss at the time of cesarean myomectomy

A detailed review of all the available techniques to reduce blood loss at the time of cesarean myomectomy is beyond the scope of this editorial. All gynecologists know that control of uterine blood flow through the uterine artery, infundibulopelvic vessels and internal iliac artery can help to reduce bleeding at the time of myomectomy. Tourniquets, vascular clamps, and artery ligation all have been reported to be useful at the time of cesarean myomectomy. In addition, intravenous infusion of oxytocin and tranexamic acid is often used at the time of cesarean myomectomy. Direct injection of uterotonics, including carbetocin, oxytocin, and vasopressin, into the uterus also has been reported. Cell saver blood salvage technology has been utilized in a limited number of cases of cesarean myomectomy.^8,18,19

Medicine is not a static field

Discoveries and new data help guide advances in medical practice. After 6 decades of strict adherence to the advice that myomectomy in pregnancy should be avoided at all costs, including at caesarean delivery, new data indicate that in carefully selected cases cesarean myomectomy is an acceptable operation. ●

Karlsson T, Johansson T, Hoguland J, et al. Time-dependent effects of oral contraceptive use on breast, ovarian and endometrial cancers. Cancer Research. 2020;canres.2476.2020. doi:10.1158/0008-5472.CAN-20-2476.

EXPERT COMMENTARY

The long-term effects of OC use on gynecologic and breast cancers has been uncertain, with different reports yielding conflicting findings. To assess the time-dependent and long-term associations between OC use and the risk of breast, ovarian, and endometrial cancer in women born between 1939 and 1970, Karlsson and colleagues used data from the UK Biobank (which includes a large cross-sectional cohort of individuals recruited between 2006 and 2010) and national databases.

Details of the study

A total of 256,661 women were included in this study. Of these, 82% (210,443) had used or were currently using OC (ever-users) and 18% (46,218) had never used OC (never-users). There were 17,739; 1,966; and 2,462 cases of breast, ovarian, and endometrial cancer, respectively, identified.

In analyses adjusted for 10 parameters, the ORs for ovarian (OR, 0.72) and endometrial cancer (OR, 0.68) were lower among ever-users of OC compared with never-users (P<.05). However, the OR for breast cancer (OR, 1.02) was similar among ever-users and never-users of OC (P>.05).

Among women followed to age 55, results were similar for the 2 gynecologic cancers but were significantly higher for breast cancer (OR, 1.10; P<.05). With 20 or more years of OC use, greater prevention of ovarian (OR, 0.60) and, particularly, endometrial cancer (OR, 0.36) was observed (P<.05). However, the risk of breast cancer was similar in never-users and long-term users of OC.

Study strengths and limitations

A strength of this study is that, compared with most previous studies, it had a much longer follow-up period.

The authors noted, however, that among the potential limitations in the study design was the fact that only 6% of participants invited to the UK Biobank volunteered to participate in the study. This may have resulted in participation bias within the cohort, reflecting a healthier cohort that is not representative of the overall population. ●

Karlsson T, Johansson T, Hoguland J, et al. Time-dependent effects of oral contraceptive use on breast, ovarian and endometrial cancers. Cancer Research. 2020;canres.2476.2020. doi:10.1158/0008-5472.CAN-20-2476.

EXPERT COMMENTARY

The long-term effects of OC use on gynecologic and breast cancers has been uncertain, with different reports yielding conflicting findings. To assess the time-dependent and long-term associations between OC use and the risk of breast, ovarian, and endometrial cancer in women born between 1939 and 1970, Karlsson and colleagues used data from the UK Biobank (which includes a large cross-sectional cohort of individuals recruited between 2006 and 2010) and national databases.

Details of the study

A total of 256,661 women were included in this study. Of these, 82% (210,443) had used or were currently using OC (ever-users) and 18% (46,218) had never used OC (never-users). There were 17,739; 1,966; and 2,462 cases of breast, ovarian, and endometrial cancer, respectively, identified.

In analyses adjusted for 10 parameters, the ORs for ovarian (OR, 0.72) and endometrial cancer (OR, 0.68) were lower among ever-users of OC compared with never-users (P<.05). However, the OR for breast cancer (OR, 1.02) was similar among ever-users and never-users of OC (P>.05).

Among women followed to age 55, results were similar for the 2 gynecologic cancers but were significantly higher for breast cancer (OR, 1.10; P<.05). With 20 or more years of OC use, greater prevention of ovarian (OR, 0.60) and, particularly, endometrial cancer (OR, 0.36) was observed (P<.05). However, the risk of breast cancer was similar in never-users and long-term users of OC.

Study strengths and limitations

A strength of this study is that, compared with most previous studies, it had a much longer follow-up period.

The authors noted, however, that among the potential limitations in the study design was the fact that only 6% of participants invited to the UK Biobank volunteered to participate in the study. This may have resulted in participation bias within the cohort, reflecting a healthier cohort that is not representative of the overall population. ●

Karlsson T, Johansson T, Hoguland J, et al. Time-dependent effects of oral contraceptive use on breast, ovarian and endometrial cancers. Cancer Research. 2020;canres.2476.2020. doi:10.1158/0008-5472.CAN-20-2476.

EXPERT COMMENTARY

The long-term effects of OC use on gynecologic and breast cancers has been uncertain, with different reports yielding conflicting findings. To assess the time-dependent and long-term associations between OC use and the risk of breast, ovarian, and endometrial cancer in women born between 1939 and 1970, Karlsson and colleagues used data from the UK Biobank (which includes a large cross-sectional cohort of individuals recruited between 2006 and 2010) and national databases.

Details of the study

A total of 256,661 women were included in this study. Of these, 82% (210,443) had used or were currently using OC (ever-users) and 18% (46,218) had never used OC (never-users). There were 17,739; 1,966; and 2,462 cases of breast, ovarian, and endometrial cancer, respectively, identified.

In analyses adjusted for 10 parameters, the ORs for ovarian (OR, 0.72) and endometrial cancer (OR, 0.68) were lower among ever-users of OC compared with never-users (P<.05). However, the OR for breast cancer (OR, 1.02) was similar among ever-users and never-users of OC (P>.05).

Among women followed to age 55, results were similar for the 2 gynecologic cancers but were significantly higher for breast cancer (OR, 1.10; P<.05). With 20 or more years of OC use, greater prevention of ovarian (OR, 0.60) and, particularly, endometrial cancer (OR, 0.36) was observed (P<.05). However, the risk of breast cancer was similar in never-users and long-term users of OC.

Study strengths and limitations

A strength of this study is that, compared with most previous studies, it had a much longer follow-up period.

The authors noted, however, that among the potential limitations in the study design was the fact that only 6% of participants invited to the UK Biobank volunteered to participate in the study. This may have resulted in participation bias within the cohort, reflecting a healthier cohort that is not representative of the overall population. ●

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

Postpartum hemorrhage (PPH) contin­ues to be a leading cause of maternal morbidity and mortality both worldwide and in the United States.^1-3 A PPH is defined as the cumulative blood loss of 1,000 mL or more, or blood loss accompanied by signs or symptoms of hypovolemia, within 24 hours following the birth process (including intrapartum loss).⁴

Approximately 70% to 80% of hemorrhages are due to abnormal uterine tone.⁵ Bimanual massage and medical management, the primary treatments for uterine atony, attempt to restore the normal uterine tone that compresses the vessels in the placental implantation site and limits bleeding. For women in whom the primary treatments are not effective, only uterine compression sutures in a laparotomy can achieve physiologic contracture of the uterus. The second-line treatment option, intrauterine tamponade, places pressure over the placental implantation site while distending the uterus.

In October 2020, the US Food and Drug Administration (FDA) granted clearance to a novel device that offers an alternative treatment option. The Jada System (Alydia Health), an intrauterine vacuum-induced hemorrhage control device, is placed in the uterus and uses wall suction to induce physiologic contraction of the uterus to control bleeding.⁶

In this article, within the context of a case vignette, we discuss the recent study on the Jada System and how this device can be used in the management of PPH.⁶

CASE Woman with PPH history fears repeat hemorrhage

Ms. B. is a 25-year-old woman (G2P1) who pre­sents for prenatal care at 10 weeks’ gestation. Her medical history is significant for asthma and PPH after her first delivery. When you review her prior delivery records, you learn that she had a protracted labor and delivered a healthy 10 lb 8 oz baby boy after 3 hours of pushing. After delivery, she received postpartum intravenous oxytocin followed by intramuscular uterotonics when her bleeding was heavy during her laceration repair. Her estimated blood loss at delivery was 600 mL. The team was called back to her bedside for the continued bleeding. Uterine atony was diagnosed. Although she received additional uterotonics, the bleeding continued. An intrauterine tamponade balloon was placed, and the bleeding ultimately was controlled. The total estimated blood loss (EBL) was 2.5 L, and the patient then was transfused with 2 U of packed red blood cells.

Currently, Ms. B. is very worried about having another hemorrhage as the bleeding terrified her and her partner, disrupted breastfeeding initiation while the tamponade was in place, and made her anxious about having another baby.

What steps would you take to prepare for a potential PPH in this patient?
 

Risk factors

While PPH often is unpredictable, many risk factors have been identified (TABLE).^7-9 Some risk factors are present during the antepartum period while others arise during labor. In some cases, obstetric clinicians may be able to intervene during prenatal care, such as by giving iron supplementation to address anemia. Other factors, however, are not modifiable, including multiparity, polyhydramnios, and multiple gestations. On presentation to the labor unit, new risk factors may arise, such as magnesium sulfate use, chorioamnionitis, protracted labor, or the need for general anesthesia. In addition, the presence of a fibroid uterus or a uterine inversion can impede effective uterine contractions.⁵

Various tools are available for assessing these risk factors on admission, during labor, and after delivery, such as the AWHONN postpartum hemorrhage risk assessment table and the CMQCC obstetric hemorrhage toolkit.^10,11

Continue to: CASE continued Patient’s history reveals risk factors...

You review with Ms. B. that she had several risk factors present during labor. She had a large baby and a protracted labor. Knowing her history in this pregnancy will allow the clinical team to be prepared for a potential recurrent hemorrhage and to respond proactively to bleeding.

Consider the management options

The initial treatment for PPH includes bimanual massage, oxytocin, and other uterotonics (methylergonovine, 15-methyl prostaglandin F2α, and misoprostol). While various algorithms are available on the order of treatment, a single agent has not been shown superior to others.¹² The antifibrinolytic medication tranexamic acid also was shown to reduce the risk of death from obstetric hemorrhage in the international WOMAN trial.¹³

While these agents often are used simultaneously to achieve hemostasis, their systemic effects are associated with contraindications. Specifically, F2α prostaglandins cannot be used in patients with asthma or active hepatic, pulmonary, or cardiac disease. Ergot derivatives cannot be used in patients with hypertension, pre-eclampsia, or cardiovascular disease. Given the rising rate of medical comorbidities during pregnancy, such contraindications limit the treatment options for many patients.

In cases in which medical management is not sufficient or is contraindicated for controlling hemorrhage, second-line treatment includes the use of tamponade techniques, such as intrauterine packing or balloons. The tamponade applies pressure directly to the placental implantation site for 12 to 24 hours, which allows time for the uterus to contract and return to normal tone. While this method may seem counterintuitive to achieving uterine tone, studies suggest a success rate between 75% and 86% with balloon tamponade.¹²

Third-line treatment options are increasingly invasive but should be used to prevent further maternal morbidity and mortality. These include uterine artery embolization and surgery. Uterine artery embolization is an option for a stable patient at a center with available interventional radiology services. If embolization is either not successful or not available, an exploratory laparotomy should be performed. Uterine compression sutures can be placed along with vascular ligation sutures of the uterine arteries (O’Leary sutures) and the hypogastric arteries. If all other methods have failed, a hysterectomy is the definitive treatment for hemorrhage.

CASE continued Patient desires an alternative to tamponade if needed

Following your visit, Ms. B. has an ultrasound scan that shows a dichorionic diamniotic twin pregnancy. She also has a microcytic anemia. After you discuss iron supplementation with the patient, she asks if there are any other options should medical management fail in the event of a recurrent hemorrhage. While intrauterine tamponade balloon did treat her hemorrhage, she was not happy with the length of time it had to remain in place, the discomfort while it was used, and the disruption to her planned recovery. You inform her of a new treatment option available for PPH, a vacuum-induced hemorrhage control device that was recently FDA cleared.

Continue to: New device controls bleeding fast...

New device controls bleeding fast

In 2020, D’Alton and colleagues reported on their multicenter, prospective single-arm treatment study on the effectiveness and safety of an intrauterine vacuum-induced hemorrhage control device.⁶ This device, the Jada System, uses low-level vacuum to induce uterine contraction to control bleeding from uterine atony. The prospective study, which followed a 2016 feasibility study, enrolled more than 100 women at 12 centers across the United States.^6,14 Women were eligible to participate if they delivered at a gestational age of 34 weeks or later and had an EBL between 500 and 1,000 mL after a vaginal delivery or an EBL between 1,000 and 1,500 mL after a cesarean delivery.

Treatment with the vacuum device was successful in 94% (100/106, 95% confidence interval, 88%–98%) of women, and definitive control of abnormal bleeding was achieved in a median of 3 minutes (interquartile range [IQR], 2.0–5.0) after connection to the vacuum device.⁶

CASE continued Patient has questions

Your patient expresses interest in this device, but she wants to understand how it works. Would it require transfer to another unit or prolonged monitoring?

How the device works

Compared with intrauterine tamponade balloon devices, which apply pressure by distending the uterus, the Jada System applies low-level intrauterine vacuum to facilitate the physiologic forces of uterine contractions to constrict myometrial blood vessels and achieve hemostasis.⁶ The device is made of medical-grade silicone. Its distal end, which is placed in the uterus, is an elliptical loop. The loop’s inner surface contains 20 vacuum pores protected by a shield that facilitate creation of a vacuum within the uterine cavity. The loop is soft and smooth to limit the chance of tissue damage during insertion, treatment, and removal of the device. The device’s proximal end has a vacuum connector. The vacuum source is hospital-grade wall suction, but a portable vacuum source also can be used (FIGURE 1).

Prior to placing the device, a manual sweep of the uterine cavity is performed. If needed, ultrasonography can be used with the manual sweep to ensure that there is no retained placental tissue or clot. The loop of the Jada System is then inserted in the uterine cavity, and the circular cervical seal, just outside the external cervical os, is filled with sterile water.

Low-level vacuum (80 ± 10 mm Hg) is applied so that pooled blood is evacuated from the uterus as it collapses (FIGURE 2). The volume of any ongoing bleeding is measured in the suction tubing while the uterine response to treatment can be palpated. Once there is no bleeding without any need for further treatment, the device should remain in the uterus for at least 1 hour. The suction is then turned off, and bleeding is monitored for 30 minutes. If bleeding remains controlled, the device can be removed.

CASE continued The question of complications

Ms. B. is concerned about safety and asks about potential complications with the device’s use.

Safety findings

In the prospective study and FDA review, the device was deemed safe. There were 8 possibly related adverse events (endometritis, laceration disruption, and vaginal infection), which all resolved without serious clinical sequelae. Forty women (38%) received a blood transfusion, but only 5 required 4 U or more of red blood cells.⁶

Continue to: CASE continued What do other physicians think?...

CASE continued What do other physicians think?

Your patient is curious about the time it takes for the device to work and whether other clinicians like using this new device for hemorrhage treatment.

Duration of treatment

The times to achieve uterine collapse and control of hemorrhage are both relatively short. In the prospective study, the initial collapse of the uterus took a median of 1 minute (IQR, 1–2 min) from the time of vacuum connection.⁶ Bleeding was controlled in less than 5 minutes in 82% of women, with an overall median time of 3 minutes (IQR, 2–5 min). The median duration of vacuum treatment was 144.0 minutes (IQR, 85.8–295.8 min), which includes the required minimum of 60 minutes for vacuum treatment time and 30 minutes of observation without the vacuum connected but with the device still in place.⁶

When polled, the majority of clinicians—98%—reported that the intrauterine vacuum-induced hemorrhage control device was easy to use, and 97% would recommend its use for future patients.⁶

Further, recognizing the device’s potential, the Cleveland Clinic cited it as one of the top 10 health care innovations for 2021 for offering a low-tech and minimally invasive tool for obstetric clinicians.¹⁵

CASE continued Final questions

Ms. B. thanks you for the information and asks, should she know anything else about the device?

Vacuum device vs other treatments

The study by D’Alton and colleagues was a single-arm treatment trial that did not directly compare the effectiveness of the device with that of other PPH treatment options, such as balloon tamponade.⁶ At this point, we know that clinicians can safely and quickly use the device to treat uterine atony, but we do not know if it is superior to other treatments for PPH.

Key takeaways

Postpartum hemorrhage is a leading cause of maternal morbidity and mortality. When first-line uterotonics fail, obstetric clinicians previously had only balloon tamponade or invasive procedures to treat patients. The novel intrauterine vacuum-induced hemorrhage control device takes a new approach that simulates the physiologic process of uterine contractions. The device can rapidly and effectively control abnormal postpartum uterine bleeding. More studies are needed, however, to compare the device’s effectiveness with that of other PPH treatments and to consider its use in women with more severe degrees of postpartum hemorrhage as well as its cost-effectiveness. ●

CASE Pregnant woman with abnormal vaginal discharge

A 26-year-old woman (G2P1001) at 24 weeks of gestation requests evaluation for increased frothy, whitish-gray vaginal discharge with a fishy odor. She notes that her underclothes constantly feel damp. The vaginal pH is 4.5, and the amine test is positive.

• What is the most likely diagnosis?
• What obstetrical complications may be associated with this condition?
• How should her condition be treated?

Meet our perpetrator

Bacterial vaginosis (BV) is one of the most common conditions associated with vaginal discharge among women of reproductive age. It is characterized by a polymicrobial alteration of the vaginal microbiome, and most distinctly, a relative absence of vaginal lactobacilli. This review discusses the microbiology, epidemiology, specific obstetric and gynecologic complications, clinical manifestations, diagnosis, and treatment of BV.

The role of vaginal flora

Estrogen has a fundamental role in regulating the normal state of the vagina. In a woman’s reproductive years, estrogen increases glycogen in the vaginal epithelial cells, and the increased glycogen concentration promotes colonization by lactobacilli. The lack of estrogen in pre- and postmenopausal women inhibits the growth of the vaginal lactobacilli, leading to a high vaginal pH, which facilitates the growth of bacteria, particularly anaerobes, that can cause BV.

The vaginal microbiome is polymicrobial and has been classified into at least 5 community state types (CSTs). Four CSTs are dominated by lactobacilli. A fifth CST is characterized by the absence of lactobacilli and high concentrations of obligate or facultative anaerobes.¹ The hydrogen peroxide–producing lactobacilli predominate in normal vaginal flora and make up 70% to 90% of the total microbiome. These hydrogen peroxide–producing lactobacilli are associated with reduced vaginal proinflammatory cytokines and a highly acidic vaginal pH. Both factors defend against sexually transmitted infections (STIs).²

BV is a polymicrobial disorder marked by the significant reduction in the number of vaginal lactobacilli (FIGURE 1). A recent study showed that BV is associated first with a decrease in Lactobacillus crispatus, followed by increase in Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type 1.³ The polymicrobial load is increased by a factor of up to 1,000, compared with normal vaginal flora.⁴ BV should be considered a biofilm infection caused by adherence of G vaginalis to the vaginal epithelium.⁵ This biofilm creates a favorable environment for the overgrowth of obligate anaerobic bacteria.

BMI factors into epidemiology

BV is the leading cause of vaginal discharge in reproductive-age women. In the United States, the National Health and Nutrition Examination Survey estimated a prevalence of 29% in the general population and 50% in Black women aged 14 to 49 years.⁶ In 2013, Kenyon and colleagues performed a systematic review to assess the worldwide epidemiology of BV, and the prevalence varied by country. Within the US population, rates were highest among non-Hispanic, Black women.⁷ Brookheart and colleagues demonstrated that, even after controlling for race, overweight and obese women had a higher frequency of BV compared with leaner women. In this investigation, the overall prevalence of BV was 28.1%. When categorized by body mass index (BMI), the prevalence was 21.3% in lean women, 30.4% in overweight women, and 34.5% in obese women (P<.001). The authors also found that Black women had a higher prevalence, independent of BMI, compared with White women.⁸

Complications may occur. BV is notable for having several serious sequelae in both pregnant and nonpregnant women. For obstetric patients, these sequelae include an increased risk of preterm birth; first trimester spontaneous abortion, particularly in the setting of in vitro fertilization; intra-amniotic infection; and endometritis.^9,10 The risk of preterm birth increases by a factor of 2 in infected women; however, most women with BV do not deliver preterm.⁴ The risk of endometritis is increased 6-fold in women with BV.¹¹ Nonpregnant women with BV are at increased risk for pelvic inflammatory disease, postoperative infections, and an increased susceptibility to STIs such as chlamydia, gonorrhea, herpes simplex virus, and HIV.^12-15 The risk for vaginal-cuff cellulitis and abscess after hysterectomy is increased 6-fold in the setting of BV.¹⁶

Continue to: Clinical manifestations...

Clinical manifestations

BV is characterized by a milky, homogenous, and malodorous vaginal discharge accompanied by vulvovaginal discomfort and vulvar irritation. Vaginal inflammation typically is absent. The associated odor is fishy, and this odor is accentuated when potassium hydroxide (KOH) is added to the vaginal discharge (amine or “whiff” test) or after the patient has coitus. The distinctive odor is due to the release of organic acids and polyamines that are byproducts of anaerobic bacterial metabolism of putrescine and cadaverine. This release is enhanced by exposure of vaginal secretions to alkaline substances such as KOH or semen.

Diagnostic tests and criteria. The diagnosis of BV is made using Amsel criteria or Gram stain with Nugent scoring; bacterial culture is not recommended. Amsel criteria include:

• homogenous, thin, white-gray discharge
• >20% clue cells on saline microscopy (FIGURE 2)
• a pH >4.5 of vaginal fluid
• positive KOH whiff test.

For diagnosis, 3 of the 4 Amsel criteria must be present.¹⁷ Gram stain with Nugent score typically is used for research purposes. Nugent scoring assigns a value to different bacterial morphotypes on Gram stain of vaginal secretions. A score of 7 to 10 is consistent with BV.¹⁸

Oral and topical treatments

Treatment is recommended for symptomatic patients. Treatment may reduce the risk of transmission and acquisition of other STIs. The TABLE summarizes Centers for Disease Control and Prevention (CDC) guidelines for BV treatment,¹⁹ with options including both oral and topical regimens. Oral and topical metronidazole and oral and topical clindamycin are equally effective at eradicating the local source of infection²⁰; however, only oral metronidazole and oral clindamycin are effective in preventing the systemic complications of BV. Oral metronidazole has more adverse effects than oral clindamycin—including nausea, vomiting, diarrhea, and a disulfiram-like reaction (characterized by flushing, dizziness, throbbing headache, chest and abdominal discomfort, and a distinct hangover effect in addition to nausea and vomiting). However, oral clindamycin can cause antibiotic-associated colitis and is more expensive than metronidazole.

Currently, there are no single-dose regimens for the treatment of BV readily available in the United States. Secnidazole, a 5-nitroimidazole with a longer half-life than metronidazole, (17 vs 8 hours) has been used as therapy in Europe and Asia but is not yet available commercially in the United States.²¹ Hiller and colleagues found that 1 g and 2 g secnidazole oral granules were superior to placebo in treating BV.²² A larger randomized trial comparing this regimen to standard treatment is necessary before this therapy is adopted as the standard of care.

Continue to: Managing recurrent disease...

Managing recurrent disease, a common problem. Bradshaw and colleagues noted that, although the initial treatment of BV is effective in approximately 80% of women, up to 50% have a recurrence within 12 months.²³ Data are limited regarding optimal treatment for recurrent infections; however, most regimens consist of some form of suppressive therapy. One regimen includes one full applicator of metronidazole vaginal gel 0.75% twice weekly for 6 months.²⁴ A second regimen consists of vaginal boric acid capsules 600 mg once daily at bedtime for 21 days. Upon completion of boric acid therapy, metronidazole vaginal gel 0.75% should be administered twice weekly for 6 months.²⁵ A third option is oral metronidazole 2 g and fluconazole 250 mg once every month.²⁶ Of note, boric acid can be fatal if consumed orally and is not recommended during pregnancy.

Most recently, a randomized trial evaluated the ability of L crispatus to prevent BV recurrence. After completion of standard treatment therapy with metronidazole, women were randomly assigned to receive vaginally administered L crispatus (152 patients) or placebo (76 patients) for 11 weeks. In the intention-to-treat population, recurrent BV occurred in 30% of patients in the L crispatus group and 45% of patients in the placebo group. The use of L crispatus significantly reduced recurrence of BV by one-third (P = .01; 95% confidence interval [CI], 0.44–0.87).²⁷ These findings are encouraging; however, confirmatory studies are needed before adopting this as standard of care.

Should sexual partners be treated as well? BV has not traditionally been considered an STI, and the CDC does not currently recommend treatment of partners of women who have BV. However, in women who have sex with women, the rate of BV concordance is high, and in women who have sex with men, coitus can clearly influence disease activity. Therefore, in patients with refractory BV, we recommend treatment of the sexual partner(s) with metronidazole 500 mg orally twice daily for 7 days. For women having sex with men, we also recommend consistent use of condoms, at least until the patient’s infection is better controlled.²⁸

CASE Resolved

The patient’s clinical findings are indicative of BV. This condition is associated with an increased risk of preterm delivery and intrapartum and postpartum infection. To reduce the risk of these systemic complications, she was treated with oral metronidazole 500 mg twice daily for 7 days. Within 1 week of completing treatment, she noted complete resolution of the malodorous discharge. ●

CASE Pregnant woman with abnormal vaginal discharge

A 26-year-old woman (G2P1001) at 24 weeks of gestation requests evaluation for increased frothy, whitish-gray vaginal discharge with a fishy odor. She notes that her underclothes constantly feel damp. The vaginal pH is 4.5, and the amine test is positive.

• What is the most likely diagnosis?
• What obstetrical complications may be associated with this condition?
• How should her condition be treated?

Meet our perpetrator

Bacterial vaginosis (BV) is one of the most common conditions associated with vaginal discharge among women of reproductive age. It is characterized by a polymicrobial alteration of the vaginal microbiome, and most distinctly, a relative absence of vaginal lactobacilli. This review discusses the microbiology, epidemiology, specific obstetric and gynecologic complications, clinical manifestations, diagnosis, and treatment of BV.

The role of vaginal flora

Estrogen has a fundamental role in regulating the normal state of the vagina. In a woman’s reproductive years, estrogen increases glycogen in the vaginal epithelial cells, and the increased glycogen concentration promotes colonization by lactobacilli. The lack of estrogen in pre- and postmenopausal women inhibits the growth of the vaginal lactobacilli, leading to a high vaginal pH, which facilitates the growth of bacteria, particularly anaerobes, that can cause BV.

The vaginal microbiome is polymicrobial and has been classified into at least 5 community state types (CSTs). Four CSTs are dominated by lactobacilli. A fifth CST is characterized by the absence of lactobacilli and high concentrations of obligate or facultative anaerobes.¹ The hydrogen peroxide–producing lactobacilli predominate in normal vaginal flora and make up 70% to 90% of the total microbiome. These hydrogen peroxide–producing lactobacilli are associated with reduced vaginal proinflammatory cytokines and a highly acidic vaginal pH. Both factors defend against sexually transmitted infections (STIs).²

BV is a polymicrobial disorder marked by the significant reduction in the number of vaginal lactobacilli (FIGURE 1). A recent study showed that BV is associated first with a decrease in Lactobacillus crispatus, followed by increase in Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type 1.³ The polymicrobial load is increased by a factor of up to 1,000, compared with normal vaginal flora.⁴ BV should be considered a biofilm infection caused by adherence of G vaginalis to the vaginal epithelium.⁵ This biofilm creates a favorable environment for the overgrowth of obligate anaerobic bacteria.

BMI factors into epidemiology

BV is the leading cause of vaginal discharge in reproductive-age women. In the United States, the National Health and Nutrition Examination Survey estimated a prevalence of 29% in the general population and 50% in Black women aged 14 to 49 years.⁶ In 2013, Kenyon and colleagues performed a systematic review to assess the worldwide epidemiology of BV, and the prevalence varied by country. Within the US population, rates were highest among non-Hispanic, Black women.⁷ Brookheart and colleagues demonstrated that, even after controlling for race, overweight and obese women had a higher frequency of BV compared with leaner women. In this investigation, the overall prevalence of BV was 28.1%. When categorized by body mass index (BMI), the prevalence was 21.3% in lean women, 30.4% in overweight women, and 34.5% in obese women (P<.001). The authors also found that Black women had a higher prevalence, independent of BMI, compared with White women.⁸

Complications may occur. BV is notable for having several serious sequelae in both pregnant and nonpregnant women. For obstetric patients, these sequelae include an increased risk of preterm birth; first trimester spontaneous abortion, particularly in the setting of in vitro fertilization; intra-amniotic infection; and endometritis.^9,10 The risk of preterm birth increases by a factor of 2 in infected women; however, most women with BV do not deliver preterm.⁴ The risk of endometritis is increased 6-fold in women with BV.¹¹ Nonpregnant women with BV are at increased risk for pelvic inflammatory disease, postoperative infections, and an increased susceptibility to STIs such as chlamydia, gonorrhea, herpes simplex virus, and HIV.^12-15 The risk for vaginal-cuff cellulitis and abscess after hysterectomy is increased 6-fold in the setting of BV.¹⁶

Continue to: Clinical manifestations...

Clinical manifestations

BV is characterized by a milky, homogenous, and malodorous vaginal discharge accompanied by vulvovaginal discomfort and vulvar irritation. Vaginal inflammation typically is absent. The associated odor is fishy, and this odor is accentuated when potassium hydroxide (KOH) is added to the vaginal discharge (amine or “whiff” test) or after the patient has coitus. The distinctive odor is due to the release of organic acids and polyamines that are byproducts of anaerobic bacterial metabolism of putrescine and cadaverine. This release is enhanced by exposure of vaginal secretions to alkaline substances such as KOH or semen.

Diagnostic tests and criteria. The diagnosis of BV is made using Amsel criteria or Gram stain with Nugent scoring; bacterial culture is not recommended. Amsel criteria include:

• homogenous, thin, white-gray discharge
• >20% clue cells on saline microscopy (FIGURE 2)
• a pH >4.5 of vaginal fluid
• positive KOH whiff test.

For diagnosis, 3 of the 4 Amsel criteria must be present.¹⁷ Gram stain with Nugent score typically is used for research purposes. Nugent scoring assigns a value to different bacterial morphotypes on Gram stain of vaginal secretions. A score of 7 to 10 is consistent with BV.¹⁸

Oral and topical treatments

Treatment is recommended for symptomatic patients. Treatment may reduce the risk of transmission and acquisition of other STIs. The TABLE summarizes Centers for Disease Control and Prevention (CDC) guidelines for BV treatment,¹⁹ with options including both oral and topical regimens. Oral and topical metronidazole and oral and topical clindamycin are equally effective at eradicating the local source of infection²⁰; however, only oral metronidazole and oral clindamycin are effective in preventing the systemic complications of BV. Oral metronidazole has more adverse effects than oral clindamycin—including nausea, vomiting, diarrhea, and a disulfiram-like reaction (characterized by flushing, dizziness, throbbing headache, chest and abdominal discomfort, and a distinct hangover effect in addition to nausea and vomiting). However, oral clindamycin can cause antibiotic-associated colitis and is more expensive than metronidazole.

Currently, there are no single-dose regimens for the treatment of BV readily available in the United States. Secnidazole, a 5-nitroimidazole with a longer half-life than metronidazole, (17 vs 8 hours) has been used as therapy in Europe and Asia but is not yet available commercially in the United States.²¹ Hiller and colleagues found that 1 g and 2 g secnidazole oral granules were superior to placebo in treating BV.²² A larger randomized trial comparing this regimen to standard treatment is necessary before this therapy is adopted as the standard of care.

Continue to: Managing recurrent disease...

Managing recurrent disease, a common problem. Bradshaw and colleagues noted that, although the initial treatment of BV is effective in approximately 80% of women, up to 50% have a recurrence within 12 months.²³ Data are limited regarding optimal treatment for recurrent infections; however, most regimens consist of some form of suppressive therapy. One regimen includes one full applicator of metronidazole vaginal gel 0.75% twice weekly for 6 months.²⁴ A second regimen consists of vaginal boric acid capsules 600 mg once daily at bedtime for 21 days. Upon completion of boric acid therapy, metronidazole vaginal gel 0.75% should be administered twice weekly for 6 months.²⁵ A third option is oral metronidazole 2 g and fluconazole 250 mg once every month.²⁶ Of note, boric acid can be fatal if consumed orally and is not recommended during pregnancy.

Most recently, a randomized trial evaluated the ability of L crispatus to prevent BV recurrence. After completion of standard treatment therapy with metronidazole, women were randomly assigned to receive vaginally administered L crispatus (152 patients) or placebo (76 patients) for 11 weeks. In the intention-to-treat population, recurrent BV occurred in 30% of patients in the L crispatus group and 45% of patients in the placebo group. The use of L crispatus significantly reduced recurrence of BV by one-third (P = .01; 95% confidence interval [CI], 0.44–0.87).²⁷ These findings are encouraging; however, confirmatory studies are needed before adopting this as standard of care.

Should sexual partners be treated as well? BV has not traditionally been considered an STI, and the CDC does not currently recommend treatment of partners of women who have BV. However, in women who have sex with women, the rate of BV concordance is high, and in women who have sex with men, coitus can clearly influence disease activity. Therefore, in patients with refractory BV, we recommend treatment of the sexual partner(s) with metronidazole 500 mg orally twice daily for 7 days. For women having sex with men, we also recommend consistent use of condoms, at least until the patient’s infection is better controlled.²⁸

CASE Resolved

The patient’s clinical findings are indicative of BV. This condition is associated with an increased risk of preterm delivery and intrapartum and postpartum infection. To reduce the risk of these systemic complications, she was treated with oral metronidazole 500 mg twice daily for 7 days. Within 1 week of completing treatment, she noted complete resolution of the malodorous discharge. ●

CASE Pregnant woman with abnormal vaginal discharge

A 26-year-old woman (G2P1001) at 24 weeks of gestation requests evaluation for increased frothy, whitish-gray vaginal discharge with a fishy odor. She notes that her underclothes constantly feel damp. The vaginal pH is 4.5, and the amine test is positive.

• What is the most likely diagnosis?
• What obstetrical complications may be associated with this condition?
• How should her condition be treated?

Meet our perpetrator

Bacterial vaginosis (BV) is one of the most common conditions associated with vaginal discharge among women of reproductive age. It is characterized by a polymicrobial alteration of the vaginal microbiome, and most distinctly, a relative absence of vaginal lactobacilli. This review discusses the microbiology, epidemiology, specific obstetric and gynecologic complications, clinical manifestations, diagnosis, and treatment of BV.

The role of vaginal flora

Estrogen has a fundamental role in regulating the normal state of the vagina. In a woman’s reproductive years, estrogen increases glycogen in the vaginal epithelial cells, and the increased glycogen concentration promotes colonization by lactobacilli. The lack of estrogen in pre- and postmenopausal women inhibits the growth of the vaginal lactobacilli, leading to a high vaginal pH, which facilitates the growth of bacteria, particularly anaerobes, that can cause BV.

The vaginal microbiome is polymicrobial and has been classified into at least 5 community state types (CSTs). Four CSTs are dominated by lactobacilli. A fifth CST is characterized by the absence of lactobacilli and high concentrations of obligate or facultative anaerobes.¹ The hydrogen peroxide–producing lactobacilli predominate in normal vaginal flora and make up 70% to 90% of the total microbiome. These hydrogen peroxide–producing lactobacilli are associated with reduced vaginal proinflammatory cytokines and a highly acidic vaginal pH. Both factors defend against sexually transmitted infections (STIs).²

BV is a polymicrobial disorder marked by the significant reduction in the number of vaginal lactobacilli (FIGURE 1). A recent study showed that BV is associated first with a decrease in Lactobacillus crispatus, followed by increase in Prevotella bivia, Gardnerella vaginalis, Atopobium vaginae, and Megasphaera type 1.³ The polymicrobial load is increased by a factor of up to 1,000, compared with normal vaginal flora.⁴ BV should be considered a biofilm infection caused by adherence of G vaginalis to the vaginal epithelium.⁵ This biofilm creates a favorable environment for the overgrowth of obligate anaerobic bacteria.

BMI factors into epidemiology

BV is the leading cause of vaginal discharge in reproductive-age women. In the United States, the National Health and Nutrition Examination Survey estimated a prevalence of 29% in the general population and 50% in Black women aged 14 to 49 years.⁶ In 2013, Kenyon and colleagues performed a systematic review to assess the worldwide epidemiology of BV, and the prevalence varied by country. Within the US population, rates were highest among non-Hispanic, Black women.⁷ Brookheart and colleagues demonstrated that, even after controlling for race, overweight and obese women had a higher frequency of BV compared with leaner women. In this investigation, the overall prevalence of BV was 28.1%. When categorized by body mass index (BMI), the prevalence was 21.3% in lean women, 30.4% in overweight women, and 34.5% in obese women (P<.001). The authors also found that Black women had a higher prevalence, independent of BMI, compared with White women.⁸

Complications may occur. BV is notable for having several serious sequelae in both pregnant and nonpregnant women. For obstetric patients, these sequelae include an increased risk of preterm birth; first trimester spontaneous abortion, particularly in the setting of in vitro fertilization; intra-amniotic infection; and endometritis.^9,10 The risk of preterm birth increases by a factor of 2 in infected women; however, most women with BV do not deliver preterm.⁴ The risk of endometritis is increased 6-fold in women with BV.¹¹ Nonpregnant women with BV are at increased risk for pelvic inflammatory disease, postoperative infections, and an increased susceptibility to STIs such as chlamydia, gonorrhea, herpes simplex virus, and HIV.^12-15 The risk for vaginal-cuff cellulitis and abscess after hysterectomy is increased 6-fold in the setting of BV.¹⁶

Continue to: Clinical manifestations...

Clinical manifestations

BV is characterized by a milky, homogenous, and malodorous vaginal discharge accompanied by vulvovaginal discomfort and vulvar irritation. Vaginal inflammation typically is absent. The associated odor is fishy, and this odor is accentuated when potassium hydroxide (KOH) is added to the vaginal discharge (amine or “whiff” test) or after the patient has coitus. The distinctive odor is due to the release of organic acids and polyamines that are byproducts of anaerobic bacterial metabolism of putrescine and cadaverine. This release is enhanced by exposure of vaginal secretions to alkaline substances such as KOH or semen.

Diagnostic tests and criteria. The diagnosis of BV is made using Amsel criteria or Gram stain with Nugent scoring; bacterial culture is not recommended. Amsel criteria include:

• homogenous, thin, white-gray discharge
• >20% clue cells on saline microscopy (FIGURE 2)
• a pH >4.5 of vaginal fluid
• positive KOH whiff test.

For diagnosis, 3 of the 4 Amsel criteria must be present.¹⁷ Gram stain with Nugent score typically is used for research purposes. Nugent scoring assigns a value to different bacterial morphotypes on Gram stain of vaginal secretions. A score of 7 to 10 is consistent with BV.¹⁸

Oral and topical treatments

Treatment is recommended for symptomatic patients. Treatment may reduce the risk of transmission and acquisition of other STIs. The TABLE summarizes Centers for Disease Control and Prevention (CDC) guidelines for BV treatment,¹⁹ with options including both oral and topical regimens. Oral and topical metronidazole and oral and topical clindamycin are equally effective at eradicating the local source of infection²⁰; however, only oral metronidazole and oral clindamycin are effective in preventing the systemic complications of BV. Oral metronidazole has more adverse effects than oral clindamycin—including nausea, vomiting, diarrhea, and a disulfiram-like reaction (characterized by flushing, dizziness, throbbing headache, chest and abdominal discomfort, and a distinct hangover effect in addition to nausea and vomiting). However, oral clindamycin can cause antibiotic-associated colitis and is more expensive than metronidazole.

Currently, there are no single-dose regimens for the treatment of BV readily available in the United States. Secnidazole, a 5-nitroimidazole with a longer half-life than metronidazole, (17 vs 8 hours) has been used as therapy in Europe and Asia but is not yet available commercially in the United States.²¹ Hiller and colleagues found that 1 g and 2 g secnidazole oral granules were superior to placebo in treating BV.²² A larger randomized trial comparing this regimen to standard treatment is necessary before this therapy is adopted as the standard of care.

Continue to: Managing recurrent disease...

Managing recurrent disease, a common problem. Bradshaw and colleagues noted that, although the initial treatment of BV is effective in approximately 80% of women, up to 50% have a recurrence within 12 months.²³ Data are limited regarding optimal treatment for recurrent infections; however, most regimens consist of some form of suppressive therapy. One regimen includes one full applicator of metronidazole vaginal gel 0.75% twice weekly for 6 months.²⁴ A second regimen consists of vaginal boric acid capsules 600 mg once daily at bedtime for 21 days. Upon completion of boric acid therapy, metronidazole vaginal gel 0.75% should be administered twice weekly for 6 months.²⁵ A third option is oral metronidazole 2 g and fluconazole 250 mg once every month.²⁶ Of note, boric acid can be fatal if consumed orally and is not recommended during pregnancy.

Most recently, a randomized trial evaluated the ability of L crispatus to prevent BV recurrence. After completion of standard treatment therapy with metronidazole, women were randomly assigned to receive vaginally administered L crispatus (152 patients) or placebo (76 patients) for 11 weeks. In the intention-to-treat population, recurrent BV occurred in 30% of patients in the L crispatus group and 45% of patients in the placebo group. The use of L crispatus significantly reduced recurrence of BV by one-third (P = .01; 95% confidence interval [CI], 0.44–0.87).²⁷ These findings are encouraging; however, confirmatory studies are needed before adopting this as standard of care.

Should sexual partners be treated as well? BV has not traditionally been considered an STI, and the CDC does not currently recommend treatment of partners of women who have BV. However, in women who have sex with women, the rate of BV concordance is high, and in women who have sex with men, coitus can clearly influence disease activity. Therefore, in patients with refractory BV, we recommend treatment of the sexual partner(s) with metronidazole 500 mg orally twice daily for 7 days. For women having sex with men, we also recommend consistent use of condoms, at least until the patient’s infection is better controlled.²⁸

CASE Resolved

The patient’s clinical findings are indicative of BV. This condition is associated with an increased risk of preterm delivery and intrapartum and postpartum infection. To reduce the risk of these systemic complications, she was treated with oral metronidazole 500 mg twice daily for 7 days. Within 1 week of completing treatment, she noted complete resolution of the malodorous discharge. ●

Although recent events have spurred much discourse regarding systemic racism, the issue of racism is old, very old. Unfortunately, our gynecologic surgery history is rooted in racism, with numerous documented procedures performed on enslaved women without their consent. Over the years, racism has continued to permeate gynecologic surgery in so far as access to quality care, patient outcomes, and inclusion in research. While racial disparities with regard to stage at diagnosis and survival of gynecologic malignancy has been documented, this discussion is outside the scope of this article.

Racial disparities in gyn surgery: The evidence

More data exist with regard to hysterectomy and racism than with any other gynecologic surgery. Most notably, a minimally invasive approach to hysterectomy is less likely to occur for minority women, even in universally insured patient populations and when controlling for factors predisposing patients to an abdominal approach.

Minority women undergo MIS for hysterectomy less often

Ranjit and colleagues assessed hysterectomy data between 2006 and 2010 from National TRICARE Prime and Prime Plus data to evaluate if racial differences existed in a universally insured population of US Armed Services members and their dependents. African American patients were significantly less likely than White patients to undergo a total vaginal hysterectomy (relative risk ratio [RRR], 0.63; 95% confidence interval [CI], 0.58–0.69) or total laparoscopic hysterectomy (RRR, 0.65; 95% CI, 0.60–0.71) compared with abdominal hysterectomy. Asian patients were also less likely to receive the vaginal (RRR, 0.71; 95% CI, 0.60–0.84) or laparoscopic (RRR, 0.69; 95% CI, 0.58–0.83) approach to hysterectomy than White patients.¹ These findings remained when controlled for surgery indication, suggesting that racial inequity was not attributed solely to preoperative patient factors. However, the authors could not control for specific patient factors such as body mass index and uterine weight.

Katon and colleagues reviewed data on patients who underwent hysterectomy for uterine fibroids at a Veterans Affairs hospital and found 99 excess abdominal hysterectomies were performed among Black women compared with White women. Despite controlling for predisposing factors related to abdominal surgery, facility, and geography (teaching hospital, higher volume hysterectomy), Black women were still less likely to undergo minimally invasive hysterectomy.² The difference in approach between both groups remained largely unexplained.²

Pollack and colleagues reviewed hysterectomy data from Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project State Inpatient Database and State Ambulatory Surgery Databases between 2010 and 2014 from Colorado, Florida, Maryland, New Jersey, and New York. They found that African American and Hispanic women were less likely to undergo vaginal (adjusted standardized prevalence ratio [aPR], 0.93; 95% CI, 0.90–0.96 and aPR, 0.95; 95% CI, 0.93−0.97, respectively) and laparoscopic hysterectomy (aPR, 0.90; 95% CI, 0.87−0.94 and aPR, 0.95; 95% CI, 0.92−0.98, respectively) than White women. Asian/Pacific Islander women were less likely to undergo vaginal hysterectomy (aPR, 0.88; 95% CI, 0.81−0.96). They also found that hospitals providing care to more racial/ethnic minority women performed more abdominal and fewer vaginal procedures compared with other hospitals.³

Sanei-Moghaddam and colleagues reviewed data from University of Pittsburgh Medical Center–affiliated hospitals and found that European-American women had 0.47 times lower odds of undergoing abdominal hysterectomy compared with ethnic/race minority group women. Also, traditional Medicaid and Medicare enrollees had 2- to 4-times higher odds of having an abdominal hysterectomy compared with patients with commercial insurance.⁴ Evidently, insurance and payer status and hospital, along with race, were associated with abdominal hysterectomy.

Postop complications higher among Black women. One study of the National Surgical Quality Improvement Program 2015 hysterectomy database found that Black women were more likely to undergo open hysterectomy than White women despite controlling for patient factors associated with open hysterectomy, including uterine weight (adjusted odds ratio [aOR], 2.02; 95% CI, 1.85–2.20).⁵ Black women also were more likely to develop both minor and major postoperative complications despite controlling for route of hysterectomy (major complications aOR, 1.56; 95% CI, 1.25–1.95 and minor complications aOR, 1.27; 95% CI, 1.11–1.47). Their study was limited by inability to control for surgeon volume and experience and hospital-specific factors.⁵

Hospital size and surgeon volume found to play a role in disparities. In an effort to address hospital and surgeon factors and racial disparities in minimally invasive hysterectomy, Mehta and colleagues evaluated an all payer system in Maryland. Black (reference White; aOR, 0.70; 95% CI, 0.63–0.78) and Hispanic patients (aOR, 0.62; 95% CI, 0.48–0.80) were less likely to undergo minimally invasive hysterectomy. Patients who had surgery at small- and medium-sized hospitals or by medium-volume surgeons (medium vs high volume: OR, 0.78; 95% CI, 0.71–0.87) were also more likely to undergo open hysterectomy.⁶ The study authors suggest increased utilization of higher volume surgeons for referrals or to assist lower-volume surgeons as potential solutions to address racial disparities.⁶

Continue to: Surgical outcome disparities extend beyond hysterectomy route...

While the bulk of data with regard to gynecologic surgery and racism addresses minimally invasive approach to treatment of fibroids and hysterectomy, limited data regarding ectopic pregnancy and adnexal surgery reveal similar findings. Hsu and colleagues reported that Black (adjusted risk ratio [aRR], 0.76; 95% CI, 0.69–0.85) and Hispanic (aRR, 0.80; 95% CI, 0.66–0.96) women treated surgically for ectopic pregnancy were less likely to undergo tubal-sparing procedures than White women.⁷ Their study did not control for human chorionic gonadotropin levels, ectopic size, or comorbidities as measured by the Elixhauser Comorbidity Index.

The data regarding gynecologic surgery and racial inequity are sparse but manifest differences that are unexplained entirely by patient payer status and individual patient factors. Studies do confirm hospital and surgeon characteristics play a part in provision of minimally invasive hysterectomy.

Forming a conceptual re-framework to achieve health equity

The centuries-long impact of racism on our field, and more specifically on gynecologic surgery, will take time and a conscious effort to overcome. In 2001, the Institute of Medicine outlined 6 domains for improvement, amongst them equitable care—“ensuring quality of care does not vary because of characteristics.”⁸ As highlighted above, some aspects of gynecologic surgery have proven to be inequitable, specifically in the provision of minimally invasive hysterectomy and treatment of ectopic pregnancy in Black women. The lack of studies on racism and gynecologic surgery as it pertains to other benign gynecologic conditions highlights the need for more research and measures that target each level of racism and, ultimately, achieve health equity.

Priority #1: Support and funding. In 2016, the Institute for Healthcare Improvement (IHI) published a white paper describing a framework to bring about health equity. First and foremost, institutions and individuals must prioritize health equity by obtaining leadership support and adequate funding.⁹ In August 2020, several leading obstetrics and gynecology organizations published a joint statement highlighting their initial plan of action to address racism and provide equitable care.¹⁰ As leading professional organizations prioritize equity, we can hope institutions and departments continue to do so as well.

Priority #2: Measuring the extent of the problem. Once adequate support and funding is established, the IHI recommends⁹:

• establishing structures and processes with an overseeing committee and dedicated budget
• deploying strategies with comprehensive data collection and pertinent metrics.

Continue to: Applying the levels of racism to a new framework...

Given the numerous untouched areas of research and components contributing to racial disparities in gynecologic surgery, determining a starting point can prove overwhelming. We suggest employing a conceptual framework that considers the different levels of racism (TABLE 1).

Three different levels of racism have been described previously:

• systemic/institutionalized,
• personally mediated
• internalized.^11,12

Systemic racism refers to differential access to services and goods in society and power within society, for example housing, education, medical care, and voting and representation.¹² Systemic racism is arguably the overarching form of racism. The studies by Mehta and colleagues and Pollack et al specifically highlight a lack of adequate access to minimally invasive hysterectomy and a subsequent increase in complication rates in minority race groups.^3,13 Access to care is only one example of systemic racism that requires action at multiple levels by professional organizations, hospitals, community organizations, and individual departments with multiple targeted solutions (TABLE 2).

Mediated racism. The second form of racism is personally mediated racism, in other words discrimination and prejudice formed by preconceived notions of a person based on their race.¹² In the joint statement published by the leading obstetrics and gynecology organizations in August 2020, a recognition of race as a social construct without the biological weight we have long afforded it was made explicit. This realization can be applied in the day-to-day categorization of patients and, most notably, the formation of a diagnosis and treatment plan.

A concrete example of potentially biased treatment is illustrated when limiting management options to the “unreliable” patient. Exposure to stereotypes and misinformation can develop into implicit bias and subsequently make the most intelligent, compassionate provider show behavior with microaggressions. This subtle behavior can play a major role in patient-provider communication and in turn affect care satisfaction, provider trust, and shared decision making.¹⁴ The Implicit bias Association Test or MPathic-VR virtual human simulations can be used to identify provider-specific implicit bias.^14,15

Internalized racism. Lastly, internalized racism refers to the individual’s acceptance of negative messages regarding their own abilities and worth,¹² which is seen commonly in imposter syndrome. Imposter syndrome, which is a failure to internalize one’s own successes and persistent fear of being discovered as a fraud, a condition which has been more commonly seen in ethnic minority groups.¹⁶ A patient’s internalized racism can manifest as self-devaluation and helplessness which may make a patient less likely to question their treatment.^12,17 Moreover, some evidence exists indicating that patients with diabetes identified physician discrimination and internalized racism as factors impeding shared decision making.¹⁸

The next steps first require recognition

Racial inequity has long infiltrated our medical field and the discussion surrounding the effects of racism on our patients and providers, and research, is long overdue. Although research continues to emerge regarding race inequity and gynecologic surgery, much remains to be done. In recognizing the levels of racism and the roles they play in our provision of good, equitable, patient-centered care, we—as individuals, departments, and organizations—can combat racism and strive for health equity. ●

Although recent events have spurred much discourse regarding systemic racism, the issue of racism is old, very old. Unfortunately, our gynecologic surgery history is rooted in racism, with numerous documented procedures performed on enslaved women without their consent. Over the years, racism has continued to permeate gynecologic surgery in so far as access to quality care, patient outcomes, and inclusion in research. While racial disparities with regard to stage at diagnosis and survival of gynecologic malignancy has been documented, this discussion is outside the scope of this article.

Racial disparities in gyn surgery: The evidence

More data exist with regard to hysterectomy and racism than with any other gynecologic surgery. Most notably, a minimally invasive approach to hysterectomy is less likely to occur for minority women, even in universally insured patient populations and when controlling for factors predisposing patients to an abdominal approach.

Minority women undergo MIS for hysterectomy less often

Ranjit and colleagues assessed hysterectomy data between 2006 and 2010 from National TRICARE Prime and Prime Plus data to evaluate if racial differences existed in a universally insured population of US Armed Services members and their dependents. African American patients were significantly less likely than White patients to undergo a total vaginal hysterectomy (relative risk ratio [RRR], 0.63; 95% confidence interval [CI], 0.58–0.69) or total laparoscopic hysterectomy (RRR, 0.65; 95% CI, 0.60–0.71) compared with abdominal hysterectomy. Asian patients were also less likely to receive the vaginal (RRR, 0.71; 95% CI, 0.60–0.84) or laparoscopic (RRR, 0.69; 95% CI, 0.58–0.83) approach to hysterectomy than White patients.¹ These findings remained when controlled for surgery indication, suggesting that racial inequity was not attributed solely to preoperative patient factors. However, the authors could not control for specific patient factors such as body mass index and uterine weight.

Katon and colleagues reviewed data on patients who underwent hysterectomy for uterine fibroids at a Veterans Affairs hospital and found 99 excess abdominal hysterectomies were performed among Black women compared with White women. Despite controlling for predisposing factors related to abdominal surgery, facility, and geography (teaching hospital, higher volume hysterectomy), Black women were still less likely to undergo minimally invasive hysterectomy.² The difference in approach between both groups remained largely unexplained.²

Pollack and colleagues reviewed hysterectomy data from Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project State Inpatient Database and State Ambulatory Surgery Databases between 2010 and 2014 from Colorado, Florida, Maryland, New Jersey, and New York. They found that African American and Hispanic women were less likely to undergo vaginal (adjusted standardized prevalence ratio [aPR], 0.93; 95% CI, 0.90–0.96 and aPR, 0.95; 95% CI, 0.93−0.97, respectively) and laparoscopic hysterectomy (aPR, 0.90; 95% CI, 0.87−0.94 and aPR, 0.95; 95% CI, 0.92−0.98, respectively) than White women. Asian/Pacific Islander women were less likely to undergo vaginal hysterectomy (aPR, 0.88; 95% CI, 0.81−0.96). They also found that hospitals providing care to more racial/ethnic minority women performed more abdominal and fewer vaginal procedures compared with other hospitals.³

Sanei-Moghaddam and colleagues reviewed data from University of Pittsburgh Medical Center–affiliated hospitals and found that European-American women had 0.47 times lower odds of undergoing abdominal hysterectomy compared with ethnic/race minority group women. Also, traditional Medicaid and Medicare enrollees had 2- to 4-times higher odds of having an abdominal hysterectomy compared with patients with commercial insurance.⁴ Evidently, insurance and payer status and hospital, along with race, were associated with abdominal hysterectomy.

Postop complications higher among Black women. One study of the National Surgical Quality Improvement Program 2015 hysterectomy database found that Black women were more likely to undergo open hysterectomy than White women despite controlling for patient factors associated with open hysterectomy, including uterine weight (adjusted odds ratio [aOR], 2.02; 95% CI, 1.85–2.20).⁵ Black women also were more likely to develop both minor and major postoperative complications despite controlling for route of hysterectomy (major complications aOR, 1.56; 95% CI, 1.25–1.95 and minor complications aOR, 1.27; 95% CI, 1.11–1.47). Their study was limited by inability to control for surgeon volume and experience and hospital-specific factors.⁵

Hospital size and surgeon volume found to play a role in disparities. In an effort to address hospital and surgeon factors and racial disparities in minimally invasive hysterectomy, Mehta and colleagues evaluated an all payer system in Maryland. Black (reference White; aOR, 0.70; 95% CI, 0.63–0.78) and Hispanic patients (aOR, 0.62; 95% CI, 0.48–0.80) were less likely to undergo minimally invasive hysterectomy. Patients who had surgery at small- and medium-sized hospitals or by medium-volume surgeons (medium vs high volume: OR, 0.78; 95% CI, 0.71–0.87) were also more likely to undergo open hysterectomy.⁶ The study authors suggest increased utilization of higher volume surgeons for referrals or to assist lower-volume surgeons as potential solutions to address racial disparities.⁶

Continue to: Surgical outcome disparities extend beyond hysterectomy route...

While the bulk of data with regard to gynecologic surgery and racism addresses minimally invasive approach to treatment of fibroids and hysterectomy, limited data regarding ectopic pregnancy and adnexal surgery reveal similar findings. Hsu and colleagues reported that Black (adjusted risk ratio [aRR], 0.76; 95% CI, 0.69–0.85) and Hispanic (aRR, 0.80; 95% CI, 0.66–0.96) women treated surgically for ectopic pregnancy were less likely to undergo tubal-sparing procedures than White women.⁷ Their study did not control for human chorionic gonadotropin levels, ectopic size, or comorbidities as measured by the Elixhauser Comorbidity Index.

The data regarding gynecologic surgery and racial inequity are sparse but manifest differences that are unexplained entirely by patient payer status and individual patient factors. Studies do confirm hospital and surgeon characteristics play a part in provision of minimally invasive hysterectomy.

Forming a conceptual re-framework to achieve health equity

The centuries-long impact of racism on our field, and more specifically on gynecologic surgery, will take time and a conscious effort to overcome. In 2001, the Institute of Medicine outlined 6 domains for improvement, amongst them equitable care—“ensuring quality of care does not vary because of characteristics.”⁸ As highlighted above, some aspects of gynecologic surgery have proven to be inequitable, specifically in the provision of minimally invasive hysterectomy and treatment of ectopic pregnancy in Black women. The lack of studies on racism and gynecologic surgery as it pertains to other benign gynecologic conditions highlights the need for more research and measures that target each level of racism and, ultimately, achieve health equity.

Priority #1: Support and funding. In 2016, the Institute for Healthcare Improvement (IHI) published a white paper describing a framework to bring about health equity. First and foremost, institutions and individuals must prioritize health equity by obtaining leadership support and adequate funding.⁹ In August 2020, several leading obstetrics and gynecology organizations published a joint statement highlighting their initial plan of action to address racism and provide equitable care.¹⁰ As leading professional organizations prioritize equity, we can hope institutions and departments continue to do so as well.

Priority #2: Measuring the extent of the problem. Once adequate support and funding is established, the IHI recommends⁹:

• establishing structures and processes with an overseeing committee and dedicated budget
• deploying strategies with comprehensive data collection and pertinent metrics.

Continue to: Applying the levels of racism to a new framework...

Given the numerous untouched areas of research and components contributing to racial disparities in gynecologic surgery, determining a starting point can prove overwhelming. We suggest employing a conceptual framework that considers the different levels of racism (TABLE 1).

Three different levels of racism have been described previously:

• systemic/institutionalized,
• personally mediated
• internalized.^11,12

Systemic racism refers to differential access to services and goods in society and power within society, for example housing, education, medical care, and voting and representation.¹² Systemic racism is arguably the overarching form of racism. The studies by Mehta and colleagues and Pollack et al specifically highlight a lack of adequate access to minimally invasive hysterectomy and a subsequent increase in complication rates in minority race groups.^3,13 Access to care is only one example of systemic racism that requires action at multiple levels by professional organizations, hospitals, community organizations, and individual departments with multiple targeted solutions (TABLE 2).

Mediated racism. The second form of racism is personally mediated racism, in other words discrimination and prejudice formed by preconceived notions of a person based on their race.¹² In the joint statement published by the leading obstetrics and gynecology organizations in August 2020, a recognition of race as a social construct without the biological weight we have long afforded it was made explicit. This realization can be applied in the day-to-day categorization of patients and, most notably, the formation of a diagnosis and treatment plan.

A concrete example of potentially biased treatment is illustrated when limiting management options to the “unreliable” patient. Exposure to stereotypes and misinformation can develop into implicit bias and subsequently make the most intelligent, compassionate provider show behavior with microaggressions. This subtle behavior can play a major role in patient-provider communication and in turn affect care satisfaction, provider trust, and shared decision making.¹⁴ The Implicit bias Association Test or MPathic-VR virtual human simulations can be used to identify provider-specific implicit bias.^14,15

Internalized racism. Lastly, internalized racism refers to the individual’s acceptance of negative messages regarding their own abilities and worth,¹² which is seen commonly in imposter syndrome. Imposter syndrome, which is a failure to internalize one’s own successes and persistent fear of being discovered as a fraud, a condition which has been more commonly seen in ethnic minority groups.¹⁶ A patient’s internalized racism can manifest as self-devaluation and helplessness which may make a patient less likely to question their treatment.^12,17 Moreover, some evidence exists indicating that patients with diabetes identified physician discrimination and internalized racism as factors impeding shared decision making.¹⁸

The next steps first require recognition

Racial inequity has long infiltrated our medical field and the discussion surrounding the effects of racism on our patients and providers, and research, is long overdue. Although research continues to emerge regarding race inequity and gynecologic surgery, much remains to be done. In recognizing the levels of racism and the roles they play in our provision of good, equitable, patient-centered care, we—as individuals, departments, and organizations—can combat racism and strive for health equity. ●

Although recent events have spurred much discourse regarding systemic racism, the issue of racism is old, very old. Unfortunately, our gynecologic surgery history is rooted in racism, with numerous documented procedures performed on enslaved women without their consent. Over the years, racism has continued to permeate gynecologic surgery in so far as access to quality care, patient outcomes, and inclusion in research. While racial disparities with regard to stage at diagnosis and survival of gynecologic malignancy has been documented, this discussion is outside the scope of this article.

Racial disparities in gyn surgery: The evidence

More data exist with regard to hysterectomy and racism than with any other gynecologic surgery. Most notably, a minimally invasive approach to hysterectomy is less likely to occur for minority women, even in universally insured patient populations and when controlling for factors predisposing patients to an abdominal approach.

Minority women undergo MIS for hysterectomy less often

Ranjit and colleagues assessed hysterectomy data between 2006 and 2010 from National TRICARE Prime and Prime Plus data to evaluate if racial differences existed in a universally insured population of US Armed Services members and their dependents. African American patients were significantly less likely than White patients to undergo a total vaginal hysterectomy (relative risk ratio [RRR], 0.63; 95% confidence interval [CI], 0.58–0.69) or total laparoscopic hysterectomy (RRR, 0.65; 95% CI, 0.60–0.71) compared with abdominal hysterectomy. Asian patients were also less likely to receive the vaginal (RRR, 0.71; 95% CI, 0.60–0.84) or laparoscopic (RRR, 0.69; 95% CI, 0.58–0.83) approach to hysterectomy than White patients.¹ These findings remained when controlled for surgery indication, suggesting that racial inequity was not attributed solely to preoperative patient factors. However, the authors could not control for specific patient factors such as body mass index and uterine weight.

Katon and colleagues reviewed data on patients who underwent hysterectomy for uterine fibroids at a Veterans Affairs hospital and found 99 excess abdominal hysterectomies were performed among Black women compared with White women. Despite controlling for predisposing factors related to abdominal surgery, facility, and geography (teaching hospital, higher volume hysterectomy), Black women were still less likely to undergo minimally invasive hysterectomy.² The difference in approach between both groups remained largely unexplained.²

Pollack and colleagues reviewed hysterectomy data from Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project State Inpatient Database and State Ambulatory Surgery Databases between 2010 and 2014 from Colorado, Florida, Maryland, New Jersey, and New York. They found that African American and Hispanic women were less likely to undergo vaginal (adjusted standardized prevalence ratio [aPR], 0.93; 95% CI, 0.90–0.96 and aPR, 0.95; 95% CI, 0.93−0.97, respectively) and laparoscopic hysterectomy (aPR, 0.90; 95% CI, 0.87−0.94 and aPR, 0.95; 95% CI, 0.92−0.98, respectively) than White women. Asian/Pacific Islander women were less likely to undergo vaginal hysterectomy (aPR, 0.88; 95% CI, 0.81−0.96). They also found that hospitals providing care to more racial/ethnic minority women performed more abdominal and fewer vaginal procedures compared with other hospitals.³

Sanei-Moghaddam and colleagues reviewed data from University of Pittsburgh Medical Center–affiliated hospitals and found that European-American women had 0.47 times lower odds of undergoing abdominal hysterectomy compared with ethnic/race minority group women. Also, traditional Medicaid and Medicare enrollees had 2- to 4-times higher odds of having an abdominal hysterectomy compared with patients with commercial insurance.⁴ Evidently, insurance and payer status and hospital, along with race, were associated with abdominal hysterectomy.

Postop complications higher among Black women. One study of the National Surgical Quality Improvement Program 2015 hysterectomy database found that Black women were more likely to undergo open hysterectomy than White women despite controlling for patient factors associated with open hysterectomy, including uterine weight (adjusted odds ratio [aOR], 2.02; 95% CI, 1.85–2.20).⁵ Black women also were more likely to develop both minor and major postoperative complications despite controlling for route of hysterectomy (major complications aOR, 1.56; 95% CI, 1.25–1.95 and minor complications aOR, 1.27; 95% CI, 1.11–1.47). Their study was limited by inability to control for surgeon volume and experience and hospital-specific factors.⁵

Hospital size and surgeon volume found to play a role in disparities. In an effort to address hospital and surgeon factors and racial disparities in minimally invasive hysterectomy, Mehta and colleagues evaluated an all payer system in Maryland. Black (reference White; aOR, 0.70; 95% CI, 0.63–0.78) and Hispanic patients (aOR, 0.62; 95% CI, 0.48–0.80) were less likely to undergo minimally invasive hysterectomy. Patients who had surgery at small- and medium-sized hospitals or by medium-volume surgeons (medium vs high volume: OR, 0.78; 95% CI, 0.71–0.87) were also more likely to undergo open hysterectomy.⁶ The study authors suggest increased utilization of higher volume surgeons for referrals or to assist lower-volume surgeons as potential solutions to address racial disparities.⁶

Continue to: Surgical outcome disparities extend beyond hysterectomy route...

While the bulk of data with regard to gynecologic surgery and racism addresses minimally invasive approach to treatment of fibroids and hysterectomy, limited data regarding ectopic pregnancy and adnexal surgery reveal similar findings. Hsu and colleagues reported that Black (adjusted risk ratio [aRR], 0.76; 95% CI, 0.69–0.85) and Hispanic (aRR, 0.80; 95% CI, 0.66–0.96) women treated surgically for ectopic pregnancy were less likely to undergo tubal-sparing procedures than White women.⁷ Their study did not control for human chorionic gonadotropin levels, ectopic size, or comorbidities as measured by the Elixhauser Comorbidity Index.

The data regarding gynecologic surgery and racial inequity are sparse but manifest differences that are unexplained entirely by patient payer status and individual patient factors. Studies do confirm hospital and surgeon characteristics play a part in provision of minimally invasive hysterectomy.

Forming a conceptual re-framework to achieve health equity

The centuries-long impact of racism on our field, and more specifically on gynecologic surgery, will take time and a conscious effort to overcome. In 2001, the Institute of Medicine outlined 6 domains for improvement, amongst them equitable care—“ensuring quality of care does not vary because of characteristics.”⁸ As highlighted above, some aspects of gynecologic surgery have proven to be inequitable, specifically in the provision of minimally invasive hysterectomy and treatment of ectopic pregnancy in Black women. The lack of studies on racism and gynecologic surgery as it pertains to other benign gynecologic conditions highlights the need for more research and measures that target each level of racism and, ultimately, achieve health equity.

Priority #1: Support and funding. In 2016, the Institute for Healthcare Improvement (IHI) published a white paper describing a framework to bring about health equity. First and foremost, institutions and individuals must prioritize health equity by obtaining leadership support and adequate funding.⁹ In August 2020, several leading obstetrics and gynecology organizations published a joint statement highlighting their initial plan of action to address racism and provide equitable care.¹⁰ As leading professional organizations prioritize equity, we can hope institutions and departments continue to do so as well.

Priority #2: Measuring the extent of the problem. Once adequate support and funding is established, the IHI recommends⁹:

• establishing structures and processes with an overseeing committee and dedicated budget
• deploying strategies with comprehensive data collection and pertinent metrics.

Continue to: Applying the levels of racism to a new framework...

Given the numerous untouched areas of research and components contributing to racial disparities in gynecologic surgery, determining a starting point can prove overwhelming. We suggest employing a conceptual framework that considers the different levels of racism (TABLE 1).

Three different levels of racism have been described previously:

• systemic/institutionalized,
• personally mediated
• internalized.^11,12

Systemic racism refers to differential access to services and goods in society and power within society, for example housing, education, medical care, and voting and representation.¹² Systemic racism is arguably the overarching form of racism. The studies by Mehta and colleagues and Pollack et al specifically highlight a lack of adequate access to minimally invasive hysterectomy and a subsequent increase in complication rates in minority race groups.^3,13 Access to care is only one example of systemic racism that requires action at multiple levels by professional organizations, hospitals, community organizations, and individual departments with multiple targeted solutions (TABLE 2).

Mediated racism. The second form of racism is personally mediated racism, in other words discrimination and prejudice formed by preconceived notions of a person based on their race.¹² In the joint statement published by the leading obstetrics and gynecology organizations in August 2020, a recognition of race as a social construct without the biological weight we have long afforded it was made explicit. This realization can be applied in the day-to-day categorization of patients and, most notably, the formation of a diagnosis and treatment plan.

A concrete example of potentially biased treatment is illustrated when limiting management options to the “unreliable” patient. Exposure to stereotypes and misinformation can develop into implicit bias and subsequently make the most intelligent, compassionate provider show behavior with microaggressions. This subtle behavior can play a major role in patient-provider communication and in turn affect care satisfaction, provider trust, and shared decision making.¹⁴ The Implicit bias Association Test or MPathic-VR virtual human simulations can be used to identify provider-specific implicit bias.^14,15

Internalized racism. Lastly, internalized racism refers to the individual’s acceptance of negative messages regarding their own abilities and worth,¹² which is seen commonly in imposter syndrome. Imposter syndrome, which is a failure to internalize one’s own successes and persistent fear of being discovered as a fraud, a condition which has been more commonly seen in ethnic minority groups.¹⁶ A patient’s internalized racism can manifest as self-devaluation and helplessness which may make a patient less likely to question their treatment.^12,17 Moreover, some evidence exists indicating that patients with diabetes identified physician discrimination and internalized racism as factors impeding shared decision making.¹⁸

The next steps first require recognition

Racial inequity has long infiltrated our medical field and the discussion surrounding the effects of racism on our patients and providers, and research, is long overdue. Although research continues to emerge regarding race inequity and gynecologic surgery, much remains to be done. In recognizing the levels of racism and the roles they play in our provision of good, equitable, patient-centered care, we—as individuals, departments, and organizations—can combat racism and strive for health equity. ●

Practicing evidence-based medicine, as obstetricians know, is not always possible when one does not have evidence due to lack of data or long-term experience in pregnancy. During the COVID-19 pandemic, the evidence changed so rapidly that we were compelled to alter our strategy frequently as we learned more about the impact of this disease on our vulnerable patient population. The COVID-19 pandemic taught us that, in unprecedented times, centering the safety of the patient, her child, and the health care team requires quick thinking, flexibility, and above all effective communication between team members.

Here, I share our institutional experience in providing practical obstetric care through various stages of the still-evolving COVID-19 pandemic. We based our strategy on guidance from the Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG),^1,2 and the Society for Maternal-Fetal Medicine (SMFM).^3-5 We were reminded yet again that the only constant is change and that timely but thoughtful adjustments were needed to keep up with the coronavirus.

Changes to prenatal care

Like many others, our institution has provided continued in-person outpatient prenatal care to both our low- and high-risk patients throughout each stage of the pandemic. While continuing to provide the necessary obstetric care, we made alterations to limit exposure and practice social distancing when possible.

Limiting patient support persons. One significant change was to restrict or limit support persons in the outpatient clinics based on guidelines reflecting community infection rates. Recognizing that this was not optimal for our patients’ emotional well-being, we needed to become more flexible in using technology to include family or support persons in prenatal visits and ultrasonography exams.

Altering test frequency. Using the guidance from SMFM,¹ we changed the frequency of our antenatal testing and ultrasonography exams in the following ways: We increased the duration between indicated growth ultrasonography to every 4 weeks and decreased fetal antenatal testing to weekly, with twice-weekly testing continued for the highest-risk patients. Early first-trimester ultrasonography exams were limited and, when possible, delayed until after 10 to 12 weeks’ gestation or combined with other indications (nuchal translucency). Prenatal visits for low-risk patients were spaced out using existing models if the patient was amenable, especially in early pregnancy.

Adjusting staff assignments and using telehealth. In the early part of the pandemic, we divided into 2 groups to limit the number of clinicians at any one site: a dedicated group of outpatient clinicians who saw patients in the clinic only and a dedicated group of inpatient clinicians who staffed labor and delivery and the inpatient antepartum service. Additionally, our consultative maternal-fetal medicine service transitioned to a telehealth platform and performed the majority of consults remotely. Ultrasonography exams at various sites were read remotely and pertinent findings were communicated directly to patients via phone or the telehealth platform. Amniocentesis continued to be offered.

Responding to lower COVID-19 case numbers. When the number of COVID-19 cases decreased in the summer and fall of 2020, we returned to our prepandemic in-person practices, but we continued to offer telehealth visits as an option for patients who desired it. Patients were limited to one support person.

Shifting gears again. During the second surge of COVID-19 in our region, we used our experiences from the first to transition our practices to reduce in-person contact. Appointment frequency was decreased if appropriate, and we developed a tiered system of antenatal testing frequency based on risk factors. Visitors were again restricted, with exceptions made for extenuating circumstances. Consults were transitioned to telemedicine as appropriate and ultrasonography exams were read remotely when possible to limit exposures. Given the varied experiences with telemedicine and patient preferences, patients who desired in-person consult were (and are still) offered this option.

Some patients who were interested in telehealth but unable to access the technology were offered appointments via telehealth with the use of our clinic devices. Telemedicine increased our flexibility in offering consults as one provider could see patients at different office sites in one session. We continued our routine inpatient and outpatient coverage during this time as this kept our coverage options more flexible and expanded our obstetric backup plan in response to increased rates of community infection that affected both clinicians and patients.

Coordinating care for infected patients. One vital part of our prenatal care during the COVID-19 pandemic was to coordinate with our colleagues in medical specialties to provide outpatient care for patients with confirmed or suspected COVID-19 during their period of isolation or quarantine. Patients could be seen as outpatients in a dedicated space that used appropriate personal protective equipment (PPE) for not only prenatal care but also any needed in-person evaluation for COVID-19. Our obstetric clinicians and sonographers performed exams, antenatal testing (in the form of biophysical profiles), and indicated ultrasonography exams (such as umbilical artery Doppler studies and fetal growth assessments). This required a concerted effort and excellent communication between teams to provide the necessary care in the safest manner possible.

Continue to: Universal testing on labor and delivery...

Not surprisingly, obstetric delivery volumes in our institution were not affected in the same way as elective surgery volumes. Our inpatient team continued to bring babies into the world at the same if not a higher rate than in prepandemic times. We continued elective inductions when space allowed. Our first COVID-19–positive patient was already at 40 weeks’ gestation when the result of her test, done due to exposure, was received. Creative effort among multiple specialties quickly developed her delivery plan, and she and her infant did well.

As data started coming out of the New York City obstetric experience, concern for preservation of the PPE supply and the potential for asymptomatic/presymptomatic patients led us, in consultation with our infectious disease colleagues, to institute universal testing for all antepartum and laboring patients. At first, all patients were tested on admission with our rapid in-house test. Eventually, we moved toward preoperative testing 3 to 5 days prior to scheduled cesarean deliveries in alignment with the surgical services when elective cases were reinstituted. Finally, we instituted preprocedure testing for all scheduled labor and delivery procedures, including inductions, cerclages, and fetal blood transfusions, while we still used rapid testing for patients who presented urgently or in labor.

We needed to address several considerations almost immediately after instituting universal testing, including:

• what to do in case of patient refusal to be tested
• which precautions to institute while awaiting test results
• potential postponement of elective delivery if a patient tested positive, and
• where best to deliver patients.

What we did at the beginning of the pandemic was not necessarily the same as we do in our current practice, and we expect that our procedures may need to change in the future. Derived from what we learned from others’ experience, we tailored our protocols to our own physical space, staffing capabilities, and testing limitations. We adjusted them often, with input from multiple services, based on updated policy, recommendation for isolation and quarantine durations, rates of community infection, and changes in the unit spaces. As with many things, one protocol did not fit every patient, necessitating case-by-case flexibility.

Delivery considerations

To answer some of the above questions, all patients who declined testing, were awaiting test results while in labor, or were in triage were placed in droplet and contact isolation on our unit, a practice we continue currently. Given the concern of potential aerosolization during the second stage of labor or during intubation, for any patients in those categories who required delivery, we limited the number of staff in their rooms as possible. Additional pediatric staff waited in close proximity of the room and were ready to come in if needed depending on fetal complications and gestational age. For delivery, all team members used full special pathogens precautions (N95 masks, face shields, gowns, and gloves).

Patients who were asymptomatic and tested negative for COVID-19 had and continue to have routine care from a PPE (standard gowns, gloves, face mask, and eye protection) and health care team perspective. We have allowed visitation of one support person per hospital stay for these patients throughout the pandemic.

For the majority of our experience during the pandemic, adult patients who tested positive for COVID-19 were cohorted within dedicated negative pressure units of varying levels of care. As these units included the same intensive care unit (ICU) we utilized in non-COVID times for critical obstetric patients, we had already operationalized their use and they were wired for our electronic fetal monitoring system. These rooms are adjacent to the main operating room (OR) complex, which allows for transition to a dedicated COVID-19 OR for cesarean delivery. We worked with the primary COVID-19 team, ICU team, anesthesia, and neonatal ICU team to develop a written protocol that detailed the care for our COVID-19–positive laboring and postpartum patients in this critical care COVID-19 unit.

For a time, admitted COVID-19–positive patients were not permitted to have support persons. The health care team therefore stepped in to be the patients’ support during the delivery of their child. Care of these patients required a great deal of coordination and communication between teams as well as the addition of a dedicated obstetric physician—separate from the regular labor and delivery team—assigned to care for these patients.

For pregnant patients in the emergency room or in the intermediate or floor COVID-19 units, portable fetal monitors and ultrasonography equipment were used for obstetric consults, fetal testing, and obstetrical ultrasonography as appropriate based on gestational age and medical conditions. Again, communication between teams was essential to provide seamless and timely patient care. Patients usually were admitted to the COVID-19 teams with maternal-fetal medicine or obstetric consult teams following daily; they were admitted and transferred to the ICU COVID-19 unit if delivery was necessary. To limit exposures whenever possible, coordinated care (such as exams and telephone evaluation) was performed outside of the room with the nursing and primary teams.

Continue to: Staying flexible to the changing COVID-19 environment...

Postponed in-person visits. Whenever possible, deliveries that were not medically indicated and in-person outpatient care visits were postponed until isolation/quarantine precautions could be lifted to avoid the need for special pathogens precautions, separation of mother and infant, and visitor restrictions. We did not postpone any medically indicated deliveries or appropriate care due to COVID-19 alone. As the CDC guidelines changed regarding the timing of infectivity, we had to continually re-evaluate when a patient could return to regular outpatient care instead of the COVID-19 clinic and/or be delivered.

Mother-infant separation. As outlined in an article we wrote with our pediatric colleagues, originally all infants were immediately separated from their COVID-19–positive mothers, and delayed cord clamping was not performed.⁶ We adjusted our protocols as experience and data grew regarding the risk of transmission to the newborn from asymptomatic mothers and as updated recommendations were made by ACOG and the CDC. Currently, if desired, asymptomatic mothers are not separated from their well term infants. We practice our standard delayed cord clamping technique for all patients. Masking, hand hygiene, and physical distancing are used to reduce the risk of infection transmission. Breastfeeding is encouraged if the patient desires it, either directly using precautions or supported via pumping.

Reduced workplace exposure. Along with many others, we are even more cognizant of reducing the risk of workplace exposure; thus, we conduct our daily multidisciplinary huddle and physician transition of care sign-outs. We use multiple rooms for our larger group with secure video chats, and we limit huddles to a single representative from each specialty.

Medication protocols. Early in the pandemic in our area, we limited antenatal corticosteroids for fetal lung maturity to patients who were at less than 34 weeks’ gestation, per ACOG recommendations, carefully considering necessity in the critically ill. Now, we continue to administer antenatal steroids according to our usual protocols up to 36 6/7 weeks, per ACOG and SMFM recommendations, regardless of illness severity.⁷ Nonsteroidal anti-inflammatory drug use, once limited in COVID-19–positive patients, are now used again. Additionally, we had a comprehensive venous thromboembolism (VTE) prophylaxis protocol for our obstetric patients, and we have added special consideration for prophylaxis for patients with moderate to severe illness or other VTE risk factors. While we do not perform routine circumcisions on infants of COVID-19–positive mothers, we have a process in place to provide that service after discharge when isolation precautions are lifted.

Labor accommodations. As COVID-19 cases increased in our hospital during recent months, we made one more significant change in our care protocols. To open up space in the ICU, we moved our care for asymptomatic COVID-19–positive laboring patients to our new labor and delivery unit with implemented special pathogens precautions. This is not revolutionary; many other hospitals did not have the same capability we did with our existing collaboration with the ICU for critical obstetric care. However, this change again required communication and collaboration among multiple care teams, agreement on the qualifications for delivery on labor and delivery versus in the ICU, and physical alteration of our unit to accommodate additional isolation precautions.

Visitor policy. Another change is that we have opened up the visitor policy to welcome an asymptomatic support person for the COVID-19–positive labor patient, giving special attention to adherence to isolation precautions. Our staff members have embraced this change as they have everything else, with cautious optimism and focus on keeping both the patients and the health care team safe. Our moderate to severely ill patients continue to be cared for in the COVID-19 unit in close collaboration with our infectious disease and ICU colleagues.

It’s all about teamwork

I hope I have given a clear example of our approach to providing obstetric care in the ever-changing landscape of the COVID-19 pandemic. We embraced this period of necessary change as practically and safely as possible for both our patients and our health care workers. We learned multiple times along the way that what seemed to be a good idea was not feasible, or not the ideal option, or that COVID-19 had changed the rules of the game again. Our team met daily if not more frequently, as we found we had to constantly adapt and change to each new challenge or new clinical scenario. When we struggled, it generally related to a gap in communication.

I am privileged to work with a dedicated, selfless, multidisciplinary team that rose to the occasion. They had the focused goal to provide the highest quality and safety in obstetric care while offering compassion and empathy for the experience of having a baby during a pandemic. ●

The author would like to acknowledge Danielle Prentice, DO, and Jaimie Maines, MD, for their manuscript review.

Practicing evidence-based medicine, as obstetricians know, is not always possible when one does not have evidence due to lack of data or long-term experience in pregnancy. During the COVID-19 pandemic, the evidence changed so rapidly that we were compelled to alter our strategy frequently as we learned more about the impact of this disease on our vulnerable patient population. The COVID-19 pandemic taught us that, in unprecedented times, centering the safety of the patient, her child, and the health care team requires quick thinking, flexibility, and above all effective communication between team members.

Here, I share our institutional experience in providing practical obstetric care through various stages of the still-evolving COVID-19 pandemic. We based our strategy on guidance from the Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG),^1,2 and the Society for Maternal-Fetal Medicine (SMFM).^3-5 We were reminded yet again that the only constant is change and that timely but thoughtful adjustments were needed to keep up with the coronavirus.

Changes to prenatal care

Like many others, our institution has provided continued in-person outpatient prenatal care to both our low- and high-risk patients throughout each stage of the pandemic. While continuing to provide the necessary obstetric care, we made alterations to limit exposure and practice social distancing when possible.

Limiting patient support persons. One significant change was to restrict or limit support persons in the outpatient clinics based on guidelines reflecting community infection rates. Recognizing that this was not optimal for our patients’ emotional well-being, we needed to become more flexible in using technology to include family or support persons in prenatal visits and ultrasonography exams.

Altering test frequency. Using the guidance from SMFM,¹ we changed the frequency of our antenatal testing and ultrasonography exams in the following ways: We increased the duration between indicated growth ultrasonography to every 4 weeks and decreased fetal antenatal testing to weekly, with twice-weekly testing continued for the highest-risk patients. Early first-trimester ultrasonography exams were limited and, when possible, delayed until after 10 to 12 weeks’ gestation or combined with other indications (nuchal translucency). Prenatal visits for low-risk patients were spaced out using existing models if the patient was amenable, especially in early pregnancy.

Adjusting staff assignments and using telehealth. In the early part of the pandemic, we divided into 2 groups to limit the number of clinicians at any one site: a dedicated group of outpatient clinicians who saw patients in the clinic only and a dedicated group of inpatient clinicians who staffed labor and delivery and the inpatient antepartum service. Additionally, our consultative maternal-fetal medicine service transitioned to a telehealth platform and performed the majority of consults remotely. Ultrasonography exams at various sites were read remotely and pertinent findings were communicated directly to patients via phone or the telehealth platform. Amniocentesis continued to be offered.

Responding to lower COVID-19 case numbers. When the number of COVID-19 cases decreased in the summer and fall of 2020, we returned to our prepandemic in-person practices, but we continued to offer telehealth visits as an option for patients who desired it. Patients were limited to one support person.

Shifting gears again. During the second surge of COVID-19 in our region, we used our experiences from the first to transition our practices to reduce in-person contact. Appointment frequency was decreased if appropriate, and we developed a tiered system of antenatal testing frequency based on risk factors. Visitors were again restricted, with exceptions made for extenuating circumstances. Consults were transitioned to telemedicine as appropriate and ultrasonography exams were read remotely when possible to limit exposures. Given the varied experiences with telemedicine and patient preferences, patients who desired in-person consult were (and are still) offered this option.

Some patients who were interested in telehealth but unable to access the technology were offered appointments via telehealth with the use of our clinic devices. Telemedicine increased our flexibility in offering consults as one provider could see patients at different office sites in one session. We continued our routine inpatient and outpatient coverage during this time as this kept our coverage options more flexible and expanded our obstetric backup plan in response to increased rates of community infection that affected both clinicians and patients.

Coordinating care for infected patients. One vital part of our prenatal care during the COVID-19 pandemic was to coordinate with our colleagues in medical specialties to provide outpatient care for patients with confirmed or suspected COVID-19 during their period of isolation or quarantine. Patients could be seen as outpatients in a dedicated space that used appropriate personal protective equipment (PPE) for not only prenatal care but also any needed in-person evaluation for COVID-19. Our obstetric clinicians and sonographers performed exams, antenatal testing (in the form of biophysical profiles), and indicated ultrasonography exams (such as umbilical artery Doppler studies and fetal growth assessments). This required a concerted effort and excellent communication between teams to provide the necessary care in the safest manner possible.

Continue to: Universal testing on labor and delivery...

Not surprisingly, obstetric delivery volumes in our institution were not affected in the same way as elective surgery volumes. Our inpatient team continued to bring babies into the world at the same if not a higher rate than in prepandemic times. We continued elective inductions when space allowed. Our first COVID-19–positive patient was already at 40 weeks’ gestation when the result of her test, done due to exposure, was received. Creative effort among multiple specialties quickly developed her delivery plan, and she and her infant did well.

As data started coming out of the New York City obstetric experience, concern for preservation of the PPE supply and the potential for asymptomatic/presymptomatic patients led us, in consultation with our infectious disease colleagues, to institute universal testing for all antepartum and laboring patients. At first, all patients were tested on admission with our rapid in-house test. Eventually, we moved toward preoperative testing 3 to 5 days prior to scheduled cesarean deliveries in alignment with the surgical services when elective cases were reinstituted. Finally, we instituted preprocedure testing for all scheduled labor and delivery procedures, including inductions, cerclages, and fetal blood transfusions, while we still used rapid testing for patients who presented urgently or in labor.

We needed to address several considerations almost immediately after instituting universal testing, including:

• what to do in case of patient refusal to be tested
• which precautions to institute while awaiting test results
• potential postponement of elective delivery if a patient tested positive, and
• where best to deliver patients.

What we did at the beginning of the pandemic was not necessarily the same as we do in our current practice, and we expect that our procedures may need to change in the future. Derived from what we learned from others’ experience, we tailored our protocols to our own physical space, staffing capabilities, and testing limitations. We adjusted them often, with input from multiple services, based on updated policy, recommendation for isolation and quarantine durations, rates of community infection, and changes in the unit spaces. As with many things, one protocol did not fit every patient, necessitating case-by-case flexibility.

Delivery considerations

To answer some of the above questions, all patients who declined testing, were awaiting test results while in labor, or were in triage were placed in droplet and contact isolation on our unit, a practice we continue currently. Given the concern of potential aerosolization during the second stage of labor or during intubation, for any patients in those categories who required delivery, we limited the number of staff in their rooms as possible. Additional pediatric staff waited in close proximity of the room and were ready to come in if needed depending on fetal complications and gestational age. For delivery, all team members used full special pathogens precautions (N95 masks, face shields, gowns, and gloves).

Patients who were asymptomatic and tested negative for COVID-19 had and continue to have routine care from a PPE (standard gowns, gloves, face mask, and eye protection) and health care team perspective. We have allowed visitation of one support person per hospital stay for these patients throughout the pandemic.

For the majority of our experience during the pandemic, adult patients who tested positive for COVID-19 were cohorted within dedicated negative pressure units of varying levels of care. As these units included the same intensive care unit (ICU) we utilized in non-COVID times for critical obstetric patients, we had already operationalized their use and they were wired for our electronic fetal monitoring system. These rooms are adjacent to the main operating room (OR) complex, which allows for transition to a dedicated COVID-19 OR for cesarean delivery. We worked with the primary COVID-19 team, ICU team, anesthesia, and neonatal ICU team to develop a written protocol that detailed the care for our COVID-19–positive laboring and postpartum patients in this critical care COVID-19 unit.

For a time, admitted COVID-19–positive patients were not permitted to have support persons. The health care team therefore stepped in to be the patients’ support during the delivery of their child. Care of these patients required a great deal of coordination and communication between teams as well as the addition of a dedicated obstetric physician—separate from the regular labor and delivery team—assigned to care for these patients.

For pregnant patients in the emergency room or in the intermediate or floor COVID-19 units, portable fetal monitors and ultrasonography equipment were used for obstetric consults, fetal testing, and obstetrical ultrasonography as appropriate based on gestational age and medical conditions. Again, communication between teams was essential to provide seamless and timely patient care. Patients usually were admitted to the COVID-19 teams with maternal-fetal medicine or obstetric consult teams following daily; they were admitted and transferred to the ICU COVID-19 unit if delivery was necessary. To limit exposures whenever possible, coordinated care (such as exams and telephone evaluation) was performed outside of the room with the nursing and primary teams.

Continue to: Staying flexible to the changing COVID-19 environment...

Postponed in-person visits. Whenever possible, deliveries that were not medically indicated and in-person outpatient care visits were postponed until isolation/quarantine precautions could be lifted to avoid the need for special pathogens precautions, separation of mother and infant, and visitor restrictions. We did not postpone any medically indicated deliveries or appropriate care due to COVID-19 alone. As the CDC guidelines changed regarding the timing of infectivity, we had to continually re-evaluate when a patient could return to regular outpatient care instead of the COVID-19 clinic and/or be delivered.

Mother-infant separation. As outlined in an article we wrote with our pediatric colleagues, originally all infants were immediately separated from their COVID-19–positive mothers, and delayed cord clamping was not performed.⁶ We adjusted our protocols as experience and data grew regarding the risk of transmission to the newborn from asymptomatic mothers and as updated recommendations were made by ACOG and the CDC. Currently, if desired, asymptomatic mothers are not separated from their well term infants. We practice our standard delayed cord clamping technique for all patients. Masking, hand hygiene, and physical distancing are used to reduce the risk of infection transmission. Breastfeeding is encouraged if the patient desires it, either directly using precautions or supported via pumping.

Reduced workplace exposure. Along with many others, we are even more cognizant of reducing the risk of workplace exposure; thus, we conduct our daily multidisciplinary huddle and physician transition of care sign-outs. We use multiple rooms for our larger group with secure video chats, and we limit huddles to a single representative from each specialty.

Medication protocols. Early in the pandemic in our area, we limited antenatal corticosteroids for fetal lung maturity to patients who were at less than 34 weeks’ gestation, per ACOG recommendations, carefully considering necessity in the critically ill. Now, we continue to administer antenatal steroids according to our usual protocols up to 36 6/7 weeks, per ACOG and SMFM recommendations, regardless of illness severity.⁷ Nonsteroidal anti-inflammatory drug use, once limited in COVID-19–positive patients, are now used again. Additionally, we had a comprehensive venous thromboembolism (VTE) prophylaxis protocol for our obstetric patients, and we have added special consideration for prophylaxis for patients with moderate to severe illness or other VTE risk factors. While we do not perform routine circumcisions on infants of COVID-19–positive mothers, we have a process in place to provide that service after discharge when isolation precautions are lifted.

Labor accommodations. As COVID-19 cases increased in our hospital during recent months, we made one more significant change in our care protocols. To open up space in the ICU, we moved our care for asymptomatic COVID-19–positive laboring patients to our new labor and delivery unit with implemented special pathogens precautions. This is not revolutionary; many other hospitals did not have the same capability we did with our existing collaboration with the ICU for critical obstetric care. However, this change again required communication and collaboration among multiple care teams, agreement on the qualifications for delivery on labor and delivery versus in the ICU, and physical alteration of our unit to accommodate additional isolation precautions.

Visitor policy. Another change is that we have opened up the visitor policy to welcome an asymptomatic support person for the COVID-19–positive labor patient, giving special attention to adherence to isolation precautions. Our staff members have embraced this change as they have everything else, with cautious optimism and focus on keeping both the patients and the health care team safe. Our moderate to severely ill patients continue to be cared for in the COVID-19 unit in close collaboration with our infectious disease and ICU colleagues.

It’s all about teamwork

I hope I have given a clear example of our approach to providing obstetric care in the ever-changing landscape of the COVID-19 pandemic. We embraced this period of necessary change as practically and safely as possible for both our patients and our health care workers. We learned multiple times along the way that what seemed to be a good idea was not feasible, or not the ideal option, or that COVID-19 had changed the rules of the game again. Our team met daily if not more frequently, as we found we had to constantly adapt and change to each new challenge or new clinical scenario. When we struggled, it generally related to a gap in communication.

I am privileged to work with a dedicated, selfless, multidisciplinary team that rose to the occasion. They had the focused goal to provide the highest quality and safety in obstetric care while offering compassion and empathy for the experience of having a baby during a pandemic. ●

The author would like to acknowledge Danielle Prentice, DO, and Jaimie Maines, MD, for their manuscript review.

Practicing evidence-based medicine, as obstetricians know, is not always possible when one does not have evidence due to lack of data or long-term experience in pregnancy. During the COVID-19 pandemic, the evidence changed so rapidly that we were compelled to alter our strategy frequently as we learned more about the impact of this disease on our vulnerable patient population. The COVID-19 pandemic taught us that, in unprecedented times, centering the safety of the patient, her child, and the health care team requires quick thinking, flexibility, and above all effective communication between team members.

Here, I share our institutional experience in providing practical obstetric care through various stages of the still-evolving COVID-19 pandemic. We based our strategy on guidance from the Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG),^1,2 and the Society for Maternal-Fetal Medicine (SMFM).^3-5 We were reminded yet again that the only constant is change and that timely but thoughtful adjustments were needed to keep up with the coronavirus.

Changes to prenatal care

Like many others, our institution has provided continued in-person outpatient prenatal care to both our low- and high-risk patients throughout each stage of the pandemic. While continuing to provide the necessary obstetric care, we made alterations to limit exposure and practice social distancing when possible.

Limiting patient support persons. One significant change was to restrict or limit support persons in the outpatient clinics based on guidelines reflecting community infection rates. Recognizing that this was not optimal for our patients’ emotional well-being, we needed to become more flexible in using technology to include family or support persons in prenatal visits and ultrasonography exams.

Altering test frequency. Using the guidance from SMFM,¹ we changed the frequency of our antenatal testing and ultrasonography exams in the following ways: We increased the duration between indicated growth ultrasonography to every 4 weeks and decreased fetal antenatal testing to weekly, with twice-weekly testing continued for the highest-risk patients. Early first-trimester ultrasonography exams were limited and, when possible, delayed until after 10 to 12 weeks’ gestation or combined with other indications (nuchal translucency). Prenatal visits for low-risk patients were spaced out using existing models if the patient was amenable, especially in early pregnancy.

Adjusting staff assignments and using telehealth. In the early part of the pandemic, we divided into 2 groups to limit the number of clinicians at any one site: a dedicated group of outpatient clinicians who saw patients in the clinic only and a dedicated group of inpatient clinicians who staffed labor and delivery and the inpatient antepartum service. Additionally, our consultative maternal-fetal medicine service transitioned to a telehealth platform and performed the majority of consults remotely. Ultrasonography exams at various sites were read remotely and pertinent findings were communicated directly to patients via phone or the telehealth platform. Amniocentesis continued to be offered.

Responding to lower COVID-19 case numbers. When the number of COVID-19 cases decreased in the summer and fall of 2020, we returned to our prepandemic in-person practices, but we continued to offer telehealth visits as an option for patients who desired it. Patients were limited to one support person.

Shifting gears again. During the second surge of COVID-19 in our region, we used our experiences from the first to transition our practices to reduce in-person contact. Appointment frequency was decreased if appropriate, and we developed a tiered system of antenatal testing frequency based on risk factors. Visitors were again restricted, with exceptions made for extenuating circumstances. Consults were transitioned to telemedicine as appropriate and ultrasonography exams were read remotely when possible to limit exposures. Given the varied experiences with telemedicine and patient preferences, patients who desired in-person consult were (and are still) offered this option.

Some patients who were interested in telehealth but unable to access the technology were offered appointments via telehealth with the use of our clinic devices. Telemedicine increased our flexibility in offering consults as one provider could see patients at different office sites in one session. We continued our routine inpatient and outpatient coverage during this time as this kept our coverage options more flexible and expanded our obstetric backup plan in response to increased rates of community infection that affected both clinicians and patients.

Coordinating care for infected patients. One vital part of our prenatal care during the COVID-19 pandemic was to coordinate with our colleagues in medical specialties to provide outpatient care for patients with confirmed or suspected COVID-19 during their period of isolation or quarantine. Patients could be seen as outpatients in a dedicated space that used appropriate personal protective equipment (PPE) for not only prenatal care but also any needed in-person evaluation for COVID-19. Our obstetric clinicians and sonographers performed exams, antenatal testing (in the form of biophysical profiles), and indicated ultrasonography exams (such as umbilical artery Doppler studies and fetal growth assessments). This required a concerted effort and excellent communication between teams to provide the necessary care in the safest manner possible.

Continue to: Universal testing on labor and delivery...

Not surprisingly, obstetric delivery volumes in our institution were not affected in the same way as elective surgery volumes. Our inpatient team continued to bring babies into the world at the same if not a higher rate than in prepandemic times. We continued elective inductions when space allowed. Our first COVID-19–positive patient was already at 40 weeks’ gestation when the result of her test, done due to exposure, was received. Creative effort among multiple specialties quickly developed her delivery plan, and she and her infant did well.

As data started coming out of the New York City obstetric experience, concern for preservation of the PPE supply and the potential for asymptomatic/presymptomatic patients led us, in consultation with our infectious disease colleagues, to institute universal testing for all antepartum and laboring patients. At first, all patients were tested on admission with our rapid in-house test. Eventually, we moved toward preoperative testing 3 to 5 days prior to scheduled cesarean deliveries in alignment with the surgical services when elective cases were reinstituted. Finally, we instituted preprocedure testing for all scheduled labor and delivery procedures, including inductions, cerclages, and fetal blood transfusions, while we still used rapid testing for patients who presented urgently or in labor.

We needed to address several considerations almost immediately after instituting universal testing, including:

• what to do in case of patient refusal to be tested
• which precautions to institute while awaiting test results
• potential postponement of elective delivery if a patient tested positive, and
• where best to deliver patients.

What we did at the beginning of the pandemic was not necessarily the same as we do in our current practice, and we expect that our procedures may need to change in the future. Derived from what we learned from others’ experience, we tailored our protocols to our own physical space, staffing capabilities, and testing limitations. We adjusted them often, with input from multiple services, based on updated policy, recommendation for isolation and quarantine durations, rates of community infection, and changes in the unit spaces. As with many things, one protocol did not fit every patient, necessitating case-by-case flexibility.

Delivery considerations

To answer some of the above questions, all patients who declined testing, were awaiting test results while in labor, or were in triage were placed in droplet and contact isolation on our unit, a practice we continue currently. Given the concern of potential aerosolization during the second stage of labor or during intubation, for any patients in those categories who required delivery, we limited the number of staff in their rooms as possible. Additional pediatric staff waited in close proximity of the room and were ready to come in if needed depending on fetal complications and gestational age. For delivery, all team members used full special pathogens precautions (N95 masks, face shields, gowns, and gloves).

Patients who were asymptomatic and tested negative for COVID-19 had and continue to have routine care from a PPE (standard gowns, gloves, face mask, and eye protection) and health care team perspective. We have allowed visitation of one support person per hospital stay for these patients throughout the pandemic.

For the majority of our experience during the pandemic, adult patients who tested positive for COVID-19 were cohorted within dedicated negative pressure units of varying levels of care. As these units included the same intensive care unit (ICU) we utilized in non-COVID times for critical obstetric patients, we had already operationalized their use and they were wired for our electronic fetal monitoring system. These rooms are adjacent to the main operating room (OR) complex, which allows for transition to a dedicated COVID-19 OR for cesarean delivery. We worked with the primary COVID-19 team, ICU team, anesthesia, and neonatal ICU team to develop a written protocol that detailed the care for our COVID-19–positive laboring and postpartum patients in this critical care COVID-19 unit.

For a time, admitted COVID-19–positive patients were not permitted to have support persons. The health care team therefore stepped in to be the patients’ support during the delivery of their child. Care of these patients required a great deal of coordination and communication between teams as well as the addition of a dedicated obstetric physician—separate from the regular labor and delivery team—assigned to care for these patients.

For pregnant patients in the emergency room or in the intermediate or floor COVID-19 units, portable fetal monitors and ultrasonography equipment were used for obstetric consults, fetal testing, and obstetrical ultrasonography as appropriate based on gestational age and medical conditions. Again, communication between teams was essential to provide seamless and timely patient care. Patients usually were admitted to the COVID-19 teams with maternal-fetal medicine or obstetric consult teams following daily; they were admitted and transferred to the ICU COVID-19 unit if delivery was necessary. To limit exposures whenever possible, coordinated care (such as exams and telephone evaluation) was performed outside of the room with the nursing and primary teams.

Continue to: Staying flexible to the changing COVID-19 environment...

Postponed in-person visits. Whenever possible, deliveries that were not medically indicated and in-person outpatient care visits were postponed until isolation/quarantine precautions could be lifted to avoid the need for special pathogens precautions, separation of mother and infant, and visitor restrictions. We did not postpone any medically indicated deliveries or appropriate care due to COVID-19 alone. As the CDC guidelines changed regarding the timing of infectivity, we had to continually re-evaluate when a patient could return to regular outpatient care instead of the COVID-19 clinic and/or be delivered.

Mother-infant separation. As outlined in an article we wrote with our pediatric colleagues, originally all infants were immediately separated from their COVID-19–positive mothers, and delayed cord clamping was not performed.⁶ We adjusted our protocols as experience and data grew regarding the risk of transmission to the newborn from asymptomatic mothers and as updated recommendations were made by ACOG and the CDC. Currently, if desired, asymptomatic mothers are not separated from their well term infants. We practice our standard delayed cord clamping technique for all patients. Masking, hand hygiene, and physical distancing are used to reduce the risk of infection transmission. Breastfeeding is encouraged if the patient desires it, either directly using precautions or supported via pumping.

Reduced workplace exposure. Along with many others, we are even more cognizant of reducing the risk of workplace exposure; thus, we conduct our daily multidisciplinary huddle and physician transition of care sign-outs. We use multiple rooms for our larger group with secure video chats, and we limit huddles to a single representative from each specialty.

Medication protocols. Early in the pandemic in our area, we limited antenatal corticosteroids for fetal lung maturity to patients who were at less than 34 weeks’ gestation, per ACOG recommendations, carefully considering necessity in the critically ill. Now, we continue to administer antenatal steroids according to our usual protocols up to 36 6/7 weeks, per ACOG and SMFM recommendations, regardless of illness severity.⁷ Nonsteroidal anti-inflammatory drug use, once limited in COVID-19–positive patients, are now used again. Additionally, we had a comprehensive venous thromboembolism (VTE) prophylaxis protocol for our obstetric patients, and we have added special consideration for prophylaxis for patients with moderate to severe illness or other VTE risk factors. While we do not perform routine circumcisions on infants of COVID-19–positive mothers, we have a process in place to provide that service after discharge when isolation precautions are lifted.

Labor accommodations. As COVID-19 cases increased in our hospital during recent months, we made one more significant change in our care protocols. To open up space in the ICU, we moved our care for asymptomatic COVID-19–positive laboring patients to our new labor and delivery unit with implemented special pathogens precautions. This is not revolutionary; many other hospitals did not have the same capability we did with our existing collaboration with the ICU for critical obstetric care. However, this change again required communication and collaboration among multiple care teams, agreement on the qualifications for delivery on labor and delivery versus in the ICU, and physical alteration of our unit to accommodate additional isolation precautions.

Visitor policy. Another change is that we have opened up the visitor policy to welcome an asymptomatic support person for the COVID-19–positive labor patient, giving special attention to adherence to isolation precautions. Our staff members have embraced this change as they have everything else, with cautious optimism and focus on keeping both the patients and the health care team safe. Our moderate to severely ill patients continue to be cared for in the COVID-19 unit in close collaboration with our infectious disease and ICU colleagues.

It’s all about teamwork

I hope I have given a clear example of our approach to providing obstetric care in the ever-changing landscape of the COVID-19 pandemic. We embraced this period of necessary change as practically and safely as possible for both our patients and our health care workers. We learned multiple times along the way that what seemed to be a good idea was not feasible, or not the ideal option, or that COVID-19 had changed the rules of the game again. Our team met daily if not more frequently, as we found we had to constantly adapt and change to each new challenge or new clinical scenario. When we struggled, it generally related to a gap in communication.

I am privileged to work with a dedicated, selfless, multidisciplinary team that rose to the occasion. They had the focused goal to provide the highest quality and safety in obstetric care while offering compassion and empathy for the experience of having a baby during a pandemic. ●

The author would like to acknowledge Danielle Prentice, DO, and Jaimie Maines, MD, for their manuscript review.

Updated option for breast biopsy

Hologic announces updates to its Brevera^® Breast Biopsy System with CorLumina^® Imaging Technology. The Brevera system is designed for use with the manufacturer’s Affirm^® Prone biopsy guidance system. 

For more information, visit https://www.hologic.com.

“Mini-sponge” device shows potential to treat PPH

During a pilot study, reports Obstetrx, 9 patients, treated at the University Teaching Hospital in Lusaka, Zambia, did not respond to conventional PPH management options after vaginal birth but did respond, with bleeding resolved in 60 seconds and no adverse events, to the XSTAT device. The device was left in place for a mean time of 1 hour, and none of the patients required further surgical procedures or blood transfusions. The initial placement time of XSTAT (mean time to placement, 62 seconds) was faster than times reported for balloon uterine tamponade devices. The pilot study results were published in Obstetrics & Gynecology.

XSTAT is US Food and Drug Administration–approved to treat high-flow arterial bleeding in prehospital trauma settings, and Obstetrx is planning to submit for 510k clearance in 2022, after the conclusion of a follow-up PPH trial in 2021.

For more information, visit: https://www.obstetrx.com/.

Continue to: AI and ovulation prediction...

A woman’s fertility window is typically the 5 days leading up to ovulation, with peak fertility in the 2 to 3 days before ovulation. There are other options for measuring that fertile window, including luteinizing hormone (LH) tests; however, Prima-Temp reports that Priya predicts the fertile window an average of 2.6 days before tests for LH. Utilizing continuous core body temperature measurement, Priya detects subtle changes in temperature patterns that occur prior to ovulation. The app portion of the technology stores and analyzes the temperature measurements, for a high-tech fertility alert system that also offers clinical diagnostic support. Potential users of the Priya system are able to sign up to receive it through the product’s website.

For more information, visit: https://www.priyafertility.com.

Updated option for breast biopsy

Hologic announces updates to its Brevera^® Breast Biopsy System with CorLumina^® Imaging Technology. The Brevera system is designed for use with the manufacturer’s Affirm^® Prone biopsy guidance system. 

For more information, visit https://www.hologic.com.

“Mini-sponge” device shows potential to treat PPH

During a pilot study, reports Obstetrx, 9 patients, treated at the University Teaching Hospital in Lusaka, Zambia, did not respond to conventional PPH management options after vaginal birth but did respond, with bleeding resolved in 60 seconds and no adverse events, to the XSTAT device. The device was left in place for a mean time of 1 hour, and none of the patients required further surgical procedures or blood transfusions. The initial placement time of XSTAT (mean time to placement, 62 seconds) was faster than times reported for balloon uterine tamponade devices. The pilot study results were published in Obstetrics & Gynecology.

XSTAT is US Food and Drug Administration–approved to treat high-flow arterial bleeding in prehospital trauma settings, and Obstetrx is planning to submit for 510k clearance in 2022, after the conclusion of a follow-up PPH trial in 2021.

For more information, visit: https://www.obstetrx.com/.

Continue to: AI and ovulation prediction...

A woman’s fertility window is typically the 5 days leading up to ovulation, with peak fertility in the 2 to 3 days before ovulation. There are other options for measuring that fertile window, including luteinizing hormone (LH) tests; however, Prima-Temp reports that Priya predicts the fertile window an average of 2.6 days before tests for LH. Utilizing continuous core body temperature measurement, Priya detects subtle changes in temperature patterns that occur prior to ovulation. The app portion of the technology stores and analyzes the temperature measurements, for a high-tech fertility alert system that also offers clinical diagnostic support. Potential users of the Priya system are able to sign up to receive it through the product’s website.

For more information, visit: https://www.priyafertility.com.

Updated option for breast biopsy

Hologic announces updates to its Brevera^® Breast Biopsy System with CorLumina^® Imaging Technology. The Brevera system is designed for use with the manufacturer’s Affirm^® Prone biopsy guidance system. 

For more information, visit https://www.hologic.com.

“Mini-sponge” device shows potential to treat PPH

During a pilot study, reports Obstetrx, 9 patients, treated at the University Teaching Hospital in Lusaka, Zambia, did not respond to conventional PPH management options after vaginal birth but did respond, with bleeding resolved in 60 seconds and no adverse events, to the XSTAT device. The device was left in place for a mean time of 1 hour, and none of the patients required further surgical procedures or blood transfusions. The initial placement time of XSTAT (mean time to placement, 62 seconds) was faster than times reported for balloon uterine tamponade devices. The pilot study results were published in Obstetrics & Gynecology.

XSTAT is US Food and Drug Administration–approved to treat high-flow arterial bleeding in prehospital trauma settings, and Obstetrx is planning to submit for 510k clearance in 2022, after the conclusion of a follow-up PPH trial in 2021.

For more information, visit: https://www.obstetrx.com/.

Continue to: AI and ovulation prediction...

A woman’s fertility window is typically the 5 days leading up to ovulation, with peak fertility in the 2 to 3 days before ovulation. There are other options for measuring that fertile window, including luteinizing hormone (LH) tests; however, Prima-Temp reports that Priya predicts the fertile window an average of 2.6 days before tests for LH. Utilizing continuous core body temperature measurement, Priya detects subtle changes in temperature patterns that occur prior to ovulation. The app portion of the technology stores and analyzes the temperature measurements, for a high-tech fertility alert system that also offers clinical diagnostic support. Potential users of the Priya system are able to sign up to receive it through the product’s website.

For more information, visit: https://www.priyafertility.com.

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In this Update, we discuss several aspects of infertility and emerging technologic advances in treatment. We review an important infertility fact sheet recently issued by the World Health Organization (WHO) that provides a succinct overview of infertility causes, the rights of infertility patients, treatment challenges, and advocacy efforts. In addition, we discuss what the infertility literature reveals about reducing multiple birth rates and the technologic, financial, and social factors involved. Finally, we look at the molecular progress made in germline-editing technology and the myriad complications involved in its potential future translation to clinical phenotyping.

WHO recognizes the burden of infertility and addresses fertility care needs

World Health Organization (WHO). Infertility fact sheet. September 14, 2020. https://www.who.int/news-room/fact-sheets/detail/infertility. Accessed January 24, 2021.

The WHO published its first comprehensive infertility fact sheet in September 2020. This document is important because it validates infertility as a high-burden disease and disability that diminishes quality of life for up to 186 million individuals globally. The infertility fact sheet is a comprehensive yet focused quick read that addresses the causes of infertility, why infertility is important, challenges, and the WHO response.

Factors in infertility

Infertility is caused by different factors in women and men, yet sometimes it is unexplained, and its relative importance can vary from country to country. For women, tubal disorders (for example, postinfectious), uterine problems (fibroids, congenital), endometriosis, ovarian disorders (polycystic ovary syndrome, ovulation disorders), and endocrine imbalances are the most common factors.

For men, causes of infertility include obstruction of the reproductive tract (as after injuries or infection); hormonal disorders in the hypothalamus, pituitary, and/or testicles (for example, low testosterone); testicular failure to produce sperm (such as after cancer treatment); and abnormal sperm function and quality (low count, motility, or morphology).

Environmental and lifestyle factors— including smoking, obesity, alcohol, or toxins—can affect fertility.

Continue to: Recognizing all individuals’ fertility rights...

The WHO infertility fact sheet makes strong statements, recognizing that individuals and couples have the right to decide the number, timing, and spacing of their children. Addressing infertility is therefore an important part of realizing the right of individuals and couples to found a family. This includes heterosexual couples, same-sex partners, older persons, individuals not in sexual relationships who might require infertility management and fertility care services, and notably marginalized populations.

Addressing infertility also can help mitigate gender inequality, which has significant negative social impacts on the lives of infertile individuals, especially women. Fertility education is important to reduce the fear of infertility and contraception use in those wanting pregnancy in the future.

In most countries the biggest challenges are availability, access, and quality of interventions to address infertility. This includes the United States, where only 1 in 4 individuals receive the fertility care they need. Lack of prioritization, ineffective public health strategies, inadequate funding, and costs are barriers. Health policies need to recognize that infertility is a disease that often can be prevented, thereby reducing future costs. Comprehensive awareness and education programs, laws and policies that regulate and ensure access and the human rights of all involved, are essential.

Advocacy efforts

To address infertility and fertility care, the WHO is committed to:

• collaborate with partners on epidemiologic and etiologic research
• facilitate policy dialogue globally to frame infertility within a legal and policy framework
• support generation of data on the burden of infertility
• develop guidelines
• produce other documents of standards
• collaborate with all stakeholders to strengthen political commitment and health system capacity, and
• provide country-level technical support to develop or strengthen policies and services.

For your practice, this means that infertility is recognized as a disease that should receive its appropriate share of health care resources. Infertility and fertility care are the right of every individual according to their desires to found a family. Besides providing the best care you can to all your patients, including referring them when necessary, all health care clinicians should advocate on behalf of their patients to payors, policy makers, and the public the need to provide equitable laws, resources, and funding for infertility and fertility care.

Continue to: Lessons learned in reducing multiple pregnancy rates in infertility treatment...

Lessons learned in reducing multiple pregnancy rates in infertility treatment

Views and reviews section. Fertil Steril. 2020;114:671- 672; 673-679; 680-689; 690-714; 715-721.

In the October 2020 issue of Fertility and Sterility, the Views and Reviews section included 5 articles on avoiding multiple live birth rates (LBRs) in assisted reproductive technologies (ART).^1-5 International experts provided a comprehensive review of global multiple LBRs and their associated negative impact on maternal and perinatal outcomes, reasons for global variability, strategies to reduce multiples, single embryo transfer, and implications of funding and reporting. These international comparisons and recommendations are helpful and applicable to infertility care in the United States.³

The rise of multiple birth rates

During the first decade of in vitro fertilization (IVF), live birth rates were low, increasing to 14% in 1990. Multiple embryos needed to be transferred so that even these LBRs could be obtained. In the 1990s, however, laboratory technology improved rapidly, with increased implantation rates and subsequent rapid increases in LBR, but also with increased multiple birth rates (MBRs).

In the United States, clinic-specific reporting helped create competition among clinics for the best LBRs, and this led to MBRs of 30% and higher. Numerous studies documented the associated significantly increased morbidity and mortality of both mothers and babies. Similar situations occurred in many other countries while some, especially Nordic nations, Australia, New Zealand, and Japan, had twin rates of less than 10% or even 5% since the early 2000s. So why the difference?

The higher MBR is due largely to the transfer of more than one embryo. The immediate solution is therefore always to perform elective single embryo transfer (eSET). However, numerous factors affect the decision to perform eSET or not, and this ideal is far from being achieved. Older women, those with longer duration of infertility and/or failed treatment, often feel a time pressure and want to transfer more embryos. Of course, biologically this is reasonable because the number and quality of their embryos is lower. While attempts have been made to assess embryo quality with preimplantation genetic testing for aneuploidy, evidence that this increases the LBR is controversial except possibly in women aged 35 to 38 years. This is especially true when the cumulative LBR, that is, the number of live births after transfer of all embryos from an egg retrieval cycle, is the measured outcome.

The major factor that determines the frequency of eSET is financial. Affordability is the out-of-pocket cost (after insurance or other subsidy) as a percentage of disposable income, and it is the most important factor that determines whether eSET is performed. Less affordable treatment creates a financial incentive to transfer more than one embryo to maximize the pregnancy rates in fewer cycles.⁵ Other factors include whether the effectiveness of treatment, that is, LBR, is emphasized over safety, that is, MBR. In the United States, the Society for Assisted Reproductive Technology now reports cumulative LBR, singleton and multiple LBR, and preterm births as outcomes, thereby increasing the emphasis on eSET.

Sociologic, cultural, and religious factors also can affect the frequency of eSET. Even within the United States, great variation exists in values and beliefs regarding infertility treatment. It can be challenging to determine who makes decisions: the patient alone, the physician, the payor, professional guidelines, or laws. In many countries, including the United States, it is an amalgam of these.

Setting new goals

If the goal is to reduce the MBR, what should that rate be? In the past few years, the MBR in the United States has been reduced to approximately 10%. It is reasonable now to set a goal of 5% in the next several years. To do this, we can learn from countries that have been successful. The United States already has very high-quality clinical and laboratory services, knowledgeable physicians, and a reasonable regulatory environment. Improved technology, specifically embryo selection for transfer, and focus on adherence to established embryo transfer guidelines could help.

Many would argue that eSET essentially should be performed always in women younger than age 40 and in all women of any age with a known euploid embryo. The major problem that drives multiples is the lack of affordability, which can be addressed by increased subsidies from payors. Increased subsidies can result from legislative mandates or societal pressures on employers, either of which could be associated with requirements for eSET and/or reduced MBRs.

In your practice, you can now reassure your infertility patients that cumulative LBRs are excellent in the United States and that the risk of multiple pregnancy has been reduced dramatically. This should encourage more patients to accept and take advantage of this successful technology that has resulted in the birth of millions of babies globally. Further reduction of the MBR to 5% should be possible within a few years through education and advocacy by women’s health care clinicians that results in increased subsidies and more affordable IVF.

Continue to: Genetics and ART...

Genetics and ART: Selection versus correction

Adashi EY, Cohen IG. The case for remedial germline editing—the long-term view. JAMA. 2020;323:1762-1763.

Rosenbaum L. The future of gene editing—toward scientific and social consensus. N Engl J Med. 2019;380:971-975.

Cyranoski D. The CRISPR-baby scandal: what’s next for human gene-editing. Nature. 2019;566:440-442.

de Wert G, Pennings G, Clarke A, et al; European Society of Human Genetics and European Society of Human Reproduction and Embryology. Human germline gene editing: recommendations of ESHG and ESHRE. Hum Reprod Open. 2018;hox025.

Following the completion of the Human Genome Project in 2003 and major technologic advancements in the subsequent years, the field of human genetics became the focal point of convergence for several distinct but interrelated disciplines: bioinformatics, computational biology, and sequencing technologies. As the result, individual human genomes can now be sequenced at a single base pair level, and with higher fidelity, at a fraction of the original cost and at a much faster speed.

This molecular progress, however, has not been accompanied by an equivalent clinical progress, because in a significant number of cases a defined and predictable clinical phenotype cannot be attributed to a detected molecular genotype. This has resulted in an overabundance of variants of uncertain significance. Variable expressivity, incomplete penetrance, epigenetics, mosaicism, and the polygenic nature of many human traits further complicate reliable interpretation and prognostication of the colossal amount of molecular genetic data that are being generated by the above-mentioned technologic advances.

Considering these limitations, at this juncture it is crucial to acknowledge that any attempts to prematurely commercialize these preclinical and research studies (such as polygenic risk scores for embryos) are perilous and have the potential to cause significant harm in terms of unnecessary stress and anxiety for intended parents as well as the potential for yet-unmapped societal and legal implications.

However, it is just a matter of time until more accurate clinical phenotyping catches up with molecular genotyping. As we get closer to this next historic milestone, precision medicine in the postnatal life (with regard to both diagnostics and therapeutics) and preimplantation genetic testing (PGT) at the prenatal stage for a much wider spectrum of conditions—including both monogenic and polygenic traits—may indeed become a reality.

The potential of germline editing

Specifically regarding PGT (which requires IVF), it is important to recognize that due to the limited and nonrenewable endowment of human oocytes (ovarian reserve), combined with the detrimental impact of advancing age on the quality of the remaining cohort as manifested by a higher risk of aneuploidy, the current clinical practice of trying to “select” a nonaffected embryo can be very inefficient. As a result, the intended parents pursuing such treatments may need to undergo multiple cycles of ovarian stimulation and oocyte retrieval.

A potential solution for genes associated with known diseases is the prospect of remedial germline editing by CRISPR–Cas9 technology or its future descendants. This would take advantage of the existing embryos to try to “correct” the defective gene instead of trying to “select” a normal embryo. These technologies are still in the early stages of development and are remotely distant from clinical applications. On the other hand, although germline gene editing, if actualized, would be a monumental breakthrough in the history of genetics and medicine, we must be cognizant of its serious legal, societal, and ethical ramifications, which are currently unknown. Furthermore, even at the biologic and technical level, the technology still is not advanced enough to reliably rule out off-target modifications, and the unintended clinical consequences of the on-target corrections have not been studied either.

Regulation of genetic modifications

Due to these myriad concerns and the lack of an existing appropriate regulatory framework and oversight for such interventions, current US law (since December 2015, through provisions in annual federal appropriations laws passed by Congress and renewed annually thereafter) bars the US Food and Drug Administration from considering any clinical trial application “in which a human embryo is intentionally created or modified to include a heritable genetic modification.” Notably, this moratorium also prohibits mitochondrial replacement technology (MRT), which is a less controversial and relatively better-studied innovation.

Mitochondrial genetic disorders caused by the mutations in mitochondrial DNA (versus nuclear DNA) are amenable to a specific treatment strategy aimed at substituting the defective maternal mitochondrial genome with the mitochondrial genome of an unaffected donor oocyte. This can be achieved via either pronuclear transfer, which involves isolation and transfer of the male and female pronuclei from an affected embryo to an enucleated normal donor embryo, or maternal spindle transfer, which involves isolation and transfer of the metaphase II spindle complex of an affected oocyte to an enucleated disease-free donor egg. It is noteworthy that in 2015 in the United Kingdom, Parliament expanded the definition of “permitted eggs and embryos” to include those “where unhealthy mitochondrial DNA is replaced by healthy mitochondrial DNA from a donor.” This thereby allows the UK Human Fertilisation and Embryology Authority to formally direct and oversee clinical trials in MRT.

Summing up

Although the future of assisted human reproduction cannot be clearly outlined at this time, it is likely to be radically different from the current state given these emerging applications at the intersection of ART and diagnostic and therapeutic genetics. To ensure that exploring this uncharted territory will ultimately be in the interest of humankind and civilization, proper regulatory oversight—after careful consideration of all ethical, societal, and legal implications—needs to be developed for all preclinical and clinical research in this field. Participatory public engagement must be an integrated part of this process. ●

In this Update, we discuss several aspects of infertility and emerging technologic advances in treatment. We review an important infertility fact sheet recently issued by the World Health Organization (WHO) that provides a succinct overview of infertility causes, the rights of infertility patients, treatment challenges, and advocacy efforts. In addition, we discuss what the infertility literature reveals about reducing multiple birth rates and the technologic, financial, and social factors involved. Finally, we look at the molecular progress made in germline-editing technology and the myriad complications involved in its potential future translation to clinical phenotyping.

WHO recognizes the burden of infertility and addresses fertility care needs

World Health Organization (WHO). Infertility fact sheet. September 14, 2020. https://www.who.int/news-room/fact-sheets/detail/infertility. Accessed January 24, 2021.

The WHO published its first comprehensive infertility fact sheet in September 2020. This document is important because it validates infertility as a high-burden disease and disability that diminishes quality of life for up to 186 million individuals globally. The infertility fact sheet is a comprehensive yet focused quick read that addresses the causes of infertility, why infertility is important, challenges, and the WHO response.

Factors in infertility

Infertility is caused by different factors in women and men, yet sometimes it is unexplained, and its relative importance can vary from country to country. For women, tubal disorders (for example, postinfectious), uterine problems (fibroids, congenital), endometriosis, ovarian disorders (polycystic ovary syndrome, ovulation disorders), and endocrine imbalances are the most common factors.

For men, causes of infertility include obstruction of the reproductive tract (as after injuries or infection); hormonal disorders in the hypothalamus, pituitary, and/or testicles (for example, low testosterone); testicular failure to produce sperm (such as after cancer treatment); and abnormal sperm function and quality (low count, motility, or morphology).

Environmental and lifestyle factors— including smoking, obesity, alcohol, or toxins—can affect fertility.

Continue to: Recognizing all individuals’ fertility rights...

The WHO infertility fact sheet makes strong statements, recognizing that individuals and couples have the right to decide the number, timing, and spacing of their children. Addressing infertility is therefore an important part of realizing the right of individuals and couples to found a family. This includes heterosexual couples, same-sex partners, older persons, individuals not in sexual relationships who might require infertility management and fertility care services, and notably marginalized populations.

Addressing infertility also can help mitigate gender inequality, which has significant negative social impacts on the lives of infertile individuals, especially women. Fertility education is important to reduce the fear of infertility and contraception use in those wanting pregnancy in the future.

In most countries the biggest challenges are availability, access, and quality of interventions to address infertility. This includes the United States, where only 1 in 4 individuals receive the fertility care they need. Lack of prioritization, ineffective public health strategies, inadequate funding, and costs are barriers. Health policies need to recognize that infertility is a disease that often can be prevented, thereby reducing future costs. Comprehensive awareness and education programs, laws and policies that regulate and ensure access and the human rights of all involved, are essential.

Advocacy efforts

To address infertility and fertility care, the WHO is committed to:

• collaborate with partners on epidemiologic and etiologic research
• facilitate policy dialogue globally to frame infertility within a legal and policy framework
• support generation of data on the burden of infertility
• develop guidelines
• produce other documents of standards
• collaborate with all stakeholders to strengthen political commitment and health system capacity, and
• provide country-level technical support to develop or strengthen policies and services.

For your practice, this means that infertility is recognized as a disease that should receive its appropriate share of health care resources. Infertility and fertility care are the right of every individual according to their desires to found a family. Besides providing the best care you can to all your patients, including referring them when necessary, all health care clinicians should advocate on behalf of their patients to payors, policy makers, and the public the need to provide equitable laws, resources, and funding for infertility and fertility care.

Continue to: Lessons learned in reducing multiple pregnancy rates in infertility treatment...

Lessons learned in reducing multiple pregnancy rates in infertility treatment

Views and reviews section. Fertil Steril. 2020;114:671- 672; 673-679; 680-689; 690-714; 715-721.

In the October 2020 issue of Fertility and Sterility, the Views and Reviews section included 5 articles on avoiding multiple live birth rates (LBRs) in assisted reproductive technologies (ART).^1-5 International experts provided a comprehensive review of global multiple LBRs and their associated negative impact on maternal and perinatal outcomes, reasons for global variability, strategies to reduce multiples, single embryo transfer, and implications of funding and reporting. These international comparisons and recommendations are helpful and applicable to infertility care in the United States.³

The rise of multiple birth rates

During the first decade of in vitro fertilization (IVF), live birth rates were low, increasing to 14% in 1990. Multiple embryos needed to be transferred so that even these LBRs could be obtained. In the 1990s, however, laboratory technology improved rapidly, with increased implantation rates and subsequent rapid increases in LBR, but also with increased multiple birth rates (MBRs).

In the United States, clinic-specific reporting helped create competition among clinics for the best LBRs, and this led to MBRs of 30% and higher. Numerous studies documented the associated significantly increased morbidity and mortality of both mothers and babies. Similar situations occurred in many other countries while some, especially Nordic nations, Australia, New Zealand, and Japan, had twin rates of less than 10% or even 5% since the early 2000s. So why the difference?

The higher MBR is due largely to the transfer of more than one embryo. The immediate solution is therefore always to perform elective single embryo transfer (eSET). However, numerous factors affect the decision to perform eSET or not, and this ideal is far from being achieved. Older women, those with longer duration of infertility and/or failed treatment, often feel a time pressure and want to transfer more embryos. Of course, biologically this is reasonable because the number and quality of their embryos is lower. While attempts have been made to assess embryo quality with preimplantation genetic testing for aneuploidy, evidence that this increases the LBR is controversial except possibly in women aged 35 to 38 years. This is especially true when the cumulative LBR, that is, the number of live births after transfer of all embryos from an egg retrieval cycle, is the measured outcome.

The major factor that determines the frequency of eSET is financial. Affordability is the out-of-pocket cost (after insurance or other subsidy) as a percentage of disposable income, and it is the most important factor that determines whether eSET is performed. Less affordable treatment creates a financial incentive to transfer more than one embryo to maximize the pregnancy rates in fewer cycles.⁵ Other factors include whether the effectiveness of treatment, that is, LBR, is emphasized over safety, that is, MBR. In the United States, the Society for Assisted Reproductive Technology now reports cumulative LBR, singleton and multiple LBR, and preterm births as outcomes, thereby increasing the emphasis on eSET.

Sociologic, cultural, and religious factors also can affect the frequency of eSET. Even within the United States, great variation exists in values and beliefs regarding infertility treatment. It can be challenging to determine who makes decisions: the patient alone, the physician, the payor, professional guidelines, or laws. In many countries, including the United States, it is an amalgam of these.

Setting new goals

If the goal is to reduce the MBR, what should that rate be? In the past few years, the MBR in the United States has been reduced to approximately 10%. It is reasonable now to set a goal of 5% in the next several years. To do this, we can learn from countries that have been successful. The United States already has very high-quality clinical and laboratory services, knowledgeable physicians, and a reasonable regulatory environment. Improved technology, specifically embryo selection for transfer, and focus on adherence to established embryo transfer guidelines could help.

Many would argue that eSET essentially should be performed always in women younger than age 40 and in all women of any age with a known euploid embryo. The major problem that drives multiples is the lack of affordability, which can be addressed by increased subsidies from payors. Increased subsidies can result from legislative mandates or societal pressures on employers, either of which could be associated with requirements for eSET and/or reduced MBRs.

In your practice, you can now reassure your infertility patients that cumulative LBRs are excellent in the United States and that the risk of multiple pregnancy has been reduced dramatically. This should encourage more patients to accept and take advantage of this successful technology that has resulted in the birth of millions of babies globally. Further reduction of the MBR to 5% should be possible within a few years through education and advocacy by women’s health care clinicians that results in increased subsidies and more affordable IVF.

Continue to: Genetics and ART...

Genetics and ART: Selection versus correction

Adashi EY, Cohen IG. The case for remedial germline editing—the long-term view. JAMA. 2020;323:1762-1763.

Rosenbaum L. The future of gene editing—toward scientific and social consensus. N Engl J Med. 2019;380:971-975.

Cyranoski D. The CRISPR-baby scandal: what’s next for human gene-editing. Nature. 2019;566:440-442.

de Wert G, Pennings G, Clarke A, et al; European Society of Human Genetics and European Society of Human Reproduction and Embryology. Human germline gene editing: recommendations of ESHG and ESHRE. Hum Reprod Open. 2018;hox025.

Following the completion of the Human Genome Project in 2003 and major technologic advancements in the subsequent years, the field of human genetics became the focal point of convergence for several distinct but interrelated disciplines: bioinformatics, computational biology, and sequencing technologies. As the result, individual human genomes can now be sequenced at a single base pair level, and with higher fidelity, at a fraction of the original cost and at a much faster speed.

This molecular progress, however, has not been accompanied by an equivalent clinical progress, because in a significant number of cases a defined and predictable clinical phenotype cannot be attributed to a detected molecular genotype. This has resulted in an overabundance of variants of uncertain significance. Variable expressivity, incomplete penetrance, epigenetics, mosaicism, and the polygenic nature of many human traits further complicate reliable interpretation and prognostication of the colossal amount of molecular genetic data that are being generated by the above-mentioned technologic advances.

Considering these limitations, at this juncture it is crucial to acknowledge that any attempts to prematurely commercialize these preclinical and research studies (such as polygenic risk scores for embryos) are perilous and have the potential to cause significant harm in terms of unnecessary stress and anxiety for intended parents as well as the potential for yet-unmapped societal and legal implications.

However, it is just a matter of time until more accurate clinical phenotyping catches up with molecular genotyping. As we get closer to this next historic milestone, precision medicine in the postnatal life (with regard to both diagnostics and therapeutics) and preimplantation genetic testing (PGT) at the prenatal stage for a much wider spectrum of conditions—including both monogenic and polygenic traits—may indeed become a reality.

The potential of germline editing

Specifically regarding PGT (which requires IVF), it is important to recognize that due to the limited and nonrenewable endowment of human oocytes (ovarian reserve), combined with the detrimental impact of advancing age on the quality of the remaining cohort as manifested by a higher risk of aneuploidy, the current clinical practice of trying to “select” a nonaffected embryo can be very inefficient. As a result, the intended parents pursuing such treatments may need to undergo multiple cycles of ovarian stimulation and oocyte retrieval.

A potential solution for genes associated with known diseases is the prospect of remedial germline editing by CRISPR–Cas9 technology or its future descendants. This would take advantage of the existing embryos to try to “correct” the defective gene instead of trying to “select” a normal embryo. These technologies are still in the early stages of development and are remotely distant from clinical applications. On the other hand, although germline gene editing, if actualized, would be a monumental breakthrough in the history of genetics and medicine, we must be cognizant of its serious legal, societal, and ethical ramifications, which are currently unknown. Furthermore, even at the biologic and technical level, the technology still is not advanced enough to reliably rule out off-target modifications, and the unintended clinical consequences of the on-target corrections have not been studied either.

Regulation of genetic modifications

Due to these myriad concerns and the lack of an existing appropriate regulatory framework and oversight for such interventions, current US law (since December 2015, through provisions in annual federal appropriations laws passed by Congress and renewed annually thereafter) bars the US Food and Drug Administration from considering any clinical trial application “in which a human embryo is intentionally created or modified to include a heritable genetic modification.” Notably, this moratorium also prohibits mitochondrial replacement technology (MRT), which is a less controversial and relatively better-studied innovation.

Mitochondrial genetic disorders caused by the mutations in mitochondrial DNA (versus nuclear DNA) are amenable to a specific treatment strategy aimed at substituting the defective maternal mitochondrial genome with the mitochondrial genome of an unaffected donor oocyte. This can be achieved via either pronuclear transfer, which involves isolation and transfer of the male and female pronuclei from an affected embryo to an enucleated normal donor embryo, or maternal spindle transfer, which involves isolation and transfer of the metaphase II spindle complex of an affected oocyte to an enucleated disease-free donor egg. It is noteworthy that in 2015 in the United Kingdom, Parliament expanded the definition of “permitted eggs and embryos” to include those “where unhealthy mitochondrial DNA is replaced by healthy mitochondrial DNA from a donor.” This thereby allows the UK Human Fertilisation and Embryology Authority to formally direct and oversee clinical trials in MRT.

Summing up

Although the future of assisted human reproduction cannot be clearly outlined at this time, it is likely to be radically different from the current state given these emerging applications at the intersection of ART and diagnostic and therapeutic genetics. To ensure that exploring this uncharted territory will ultimately be in the interest of humankind and civilization, proper regulatory oversight—after careful consideration of all ethical, societal, and legal implications—needs to be developed for all preclinical and clinical research in this field. Participatory public engagement must be an integrated part of this process. ●

In this Update, we discuss several aspects of infertility and emerging technologic advances in treatment. We review an important infertility fact sheet recently issued by the World Health Organization (WHO) that provides a succinct overview of infertility causes, the rights of infertility patients, treatment challenges, and advocacy efforts. In addition, we discuss what the infertility literature reveals about reducing multiple birth rates and the technologic, financial, and social factors involved. Finally, we look at the molecular progress made in germline-editing technology and the myriad complications involved in its potential future translation to clinical phenotyping.

WHO recognizes the burden of infertility and addresses fertility care needs

World Health Organization (WHO). Infertility fact sheet. September 14, 2020. https://www.who.int/news-room/fact-sheets/detail/infertility. Accessed January 24, 2021.

The WHO published its first comprehensive infertility fact sheet in September 2020. This document is important because it validates infertility as a high-burden disease and disability that diminishes quality of life for up to 186 million individuals globally. The infertility fact sheet is a comprehensive yet focused quick read that addresses the causes of infertility, why infertility is important, challenges, and the WHO response.

Factors in infertility

Infertility is caused by different factors in women and men, yet sometimes it is unexplained, and its relative importance can vary from country to country. For women, tubal disorders (for example, postinfectious), uterine problems (fibroids, congenital), endometriosis, ovarian disorders (polycystic ovary syndrome, ovulation disorders), and endocrine imbalances are the most common factors.

For men, causes of infertility include obstruction of the reproductive tract (as after injuries or infection); hormonal disorders in the hypothalamus, pituitary, and/or testicles (for example, low testosterone); testicular failure to produce sperm (such as after cancer treatment); and abnormal sperm function and quality (low count, motility, or morphology).

Environmental and lifestyle factors— including smoking, obesity, alcohol, or toxins—can affect fertility.

Continue to: Recognizing all individuals’ fertility rights...

The WHO infertility fact sheet makes strong statements, recognizing that individuals and couples have the right to decide the number, timing, and spacing of their children. Addressing infertility is therefore an important part of realizing the right of individuals and couples to found a family. This includes heterosexual couples, same-sex partners, older persons, individuals not in sexual relationships who might require infertility management and fertility care services, and notably marginalized populations.

Addressing infertility also can help mitigate gender inequality, which has significant negative social impacts on the lives of infertile individuals, especially women. Fertility education is important to reduce the fear of infertility and contraception use in those wanting pregnancy in the future.

In most countries the biggest challenges are availability, access, and quality of interventions to address infertility. This includes the United States, where only 1 in 4 individuals receive the fertility care they need. Lack of prioritization, ineffective public health strategies, inadequate funding, and costs are barriers. Health policies need to recognize that infertility is a disease that often can be prevented, thereby reducing future costs. Comprehensive awareness and education programs, laws and policies that regulate and ensure access and the human rights of all involved, are essential.

Advocacy efforts

To address infertility and fertility care, the WHO is committed to:

• collaborate with partners on epidemiologic and etiologic research
• facilitate policy dialogue globally to frame infertility within a legal and policy framework
• support generation of data on the burden of infertility
• develop guidelines
• produce other documents of standards
• collaborate with all stakeholders to strengthen political commitment and health system capacity, and
• provide country-level technical support to develop or strengthen policies and services.

For your practice, this means that infertility is recognized as a disease that should receive its appropriate share of health care resources. Infertility and fertility care are the right of every individual according to their desires to found a family. Besides providing the best care you can to all your patients, including referring them when necessary, all health care clinicians should advocate on behalf of their patients to payors, policy makers, and the public the need to provide equitable laws, resources, and funding for infertility and fertility care.

Continue to: Lessons learned in reducing multiple pregnancy rates in infertility treatment...

Lessons learned in reducing multiple pregnancy rates in infertility treatment

Views and reviews section. Fertil Steril. 2020;114:671- 672; 673-679; 680-689; 690-714; 715-721.

In the October 2020 issue of Fertility and Sterility, the Views and Reviews section included 5 articles on avoiding multiple live birth rates (LBRs) in assisted reproductive technologies (ART).^1-5 International experts provided a comprehensive review of global multiple LBRs and their associated negative impact on maternal and perinatal outcomes, reasons for global variability, strategies to reduce multiples, single embryo transfer, and implications of funding and reporting. These international comparisons and recommendations are helpful and applicable to infertility care in the United States.³

The rise of multiple birth rates

During the first decade of in vitro fertilization (IVF), live birth rates were low, increasing to 14% in 1990. Multiple embryos needed to be transferred so that even these LBRs could be obtained. In the 1990s, however, laboratory technology improved rapidly, with increased implantation rates and subsequent rapid increases in LBR, but also with increased multiple birth rates (MBRs).

In the United States, clinic-specific reporting helped create competition among clinics for the best LBRs, and this led to MBRs of 30% and higher. Numerous studies documented the associated significantly increased morbidity and mortality of both mothers and babies. Similar situations occurred in many other countries while some, especially Nordic nations, Australia, New Zealand, and Japan, had twin rates of less than 10% or even 5% since the early 2000s. So why the difference?

The higher MBR is due largely to the transfer of more than one embryo. The immediate solution is therefore always to perform elective single embryo transfer (eSET). However, numerous factors affect the decision to perform eSET or not, and this ideal is far from being achieved. Older women, those with longer duration of infertility and/or failed treatment, often feel a time pressure and want to transfer more embryos. Of course, biologically this is reasonable because the number and quality of their embryos is lower. While attempts have been made to assess embryo quality with preimplantation genetic testing for aneuploidy, evidence that this increases the LBR is controversial except possibly in women aged 35 to 38 years. This is especially true when the cumulative LBR, that is, the number of live births after transfer of all embryos from an egg retrieval cycle, is the measured outcome.

The major factor that determines the frequency of eSET is financial. Affordability is the out-of-pocket cost (after insurance or other subsidy) as a percentage of disposable income, and it is the most important factor that determines whether eSET is performed. Less affordable treatment creates a financial incentive to transfer more than one embryo to maximize the pregnancy rates in fewer cycles.⁵ Other factors include whether the effectiveness of treatment, that is, LBR, is emphasized over safety, that is, MBR. In the United States, the Society for Assisted Reproductive Technology now reports cumulative LBR, singleton and multiple LBR, and preterm births as outcomes, thereby increasing the emphasis on eSET.

Sociologic, cultural, and religious factors also can affect the frequency of eSET. Even within the United States, great variation exists in values and beliefs regarding infertility treatment. It can be challenging to determine who makes decisions: the patient alone, the physician, the payor, professional guidelines, or laws. In many countries, including the United States, it is an amalgam of these.

Setting new goals

If the goal is to reduce the MBR, what should that rate be? In the past few years, the MBR in the United States has been reduced to approximately 10%. It is reasonable now to set a goal of 5% in the next several years. To do this, we can learn from countries that have been successful. The United States already has very high-quality clinical and laboratory services, knowledgeable physicians, and a reasonable regulatory environment. Improved technology, specifically embryo selection for transfer, and focus on adherence to established embryo transfer guidelines could help.

Many would argue that eSET essentially should be performed always in women younger than age 40 and in all women of any age with a known euploid embryo. The major problem that drives multiples is the lack of affordability, which can be addressed by increased subsidies from payors. Increased subsidies can result from legislative mandates or societal pressures on employers, either of which could be associated with requirements for eSET and/or reduced MBRs.

In your practice, you can now reassure your infertility patients that cumulative LBRs are excellent in the United States and that the risk of multiple pregnancy has been reduced dramatically. This should encourage more patients to accept and take advantage of this successful technology that has resulted in the birth of millions of babies globally. Further reduction of the MBR to 5% should be possible within a few years through education and advocacy by women’s health care clinicians that results in increased subsidies and more affordable IVF.

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Genetics and ART: Selection versus correction

Adashi EY, Cohen IG. The case for remedial germline editing—the long-term view. JAMA. 2020;323:1762-1763.

Rosenbaum L. The future of gene editing—toward scientific and social consensus. N Engl J Med. 2019;380:971-975.

Cyranoski D. The CRISPR-baby scandal: what’s next for human gene-editing. Nature. 2019;566:440-442.

de Wert G, Pennings G, Clarke A, et al; European Society of Human Genetics and European Society of Human Reproduction and Embryology. Human germline gene editing: recommendations of ESHG and ESHRE. Hum Reprod Open. 2018;hox025.

Following the completion of the Human Genome Project in 2003 and major technologic advancements in the subsequent years, the field of human genetics became the focal point of convergence for several distinct but interrelated disciplines: bioinformatics, computational biology, and sequencing technologies. As the result, individual human genomes can now be sequenced at a single base pair level, and with higher fidelity, at a fraction of the original cost and at a much faster speed.

This molecular progress, however, has not been accompanied by an equivalent clinical progress, because in a significant number of cases a defined and predictable clinical phenotype cannot be attributed to a detected molecular genotype. This has resulted in an overabundance of variants of uncertain significance. Variable expressivity, incomplete penetrance, epigenetics, mosaicism, and the polygenic nature of many human traits further complicate reliable interpretation and prognostication of the colossal amount of molecular genetic data that are being generated by the above-mentioned technologic advances.

Considering these limitations, at this juncture it is crucial to acknowledge that any attempts to prematurely commercialize these preclinical and research studies (such as polygenic risk scores for embryos) are perilous and have the potential to cause significant harm in terms of unnecessary stress and anxiety for intended parents as well as the potential for yet-unmapped societal and legal implications.

However, it is just a matter of time until more accurate clinical phenotyping catches up with molecular genotyping. As we get closer to this next historic milestone, precision medicine in the postnatal life (with regard to both diagnostics and therapeutics) and preimplantation genetic testing (PGT) at the prenatal stage for a much wider spectrum of conditions—including both monogenic and polygenic traits—may indeed become a reality.

The potential of germline editing

Specifically regarding PGT (which requires IVF), it is important to recognize that due to the limited and nonrenewable endowment of human oocytes (ovarian reserve), combined with the detrimental impact of advancing age on the quality of the remaining cohort as manifested by a higher risk of aneuploidy, the current clinical practice of trying to “select” a nonaffected embryo can be very inefficient. As a result, the intended parents pursuing such treatments may need to undergo multiple cycles of ovarian stimulation and oocyte retrieval.

A potential solution for genes associated with known diseases is the prospect of remedial germline editing by CRISPR–Cas9 technology or its future descendants. This would take advantage of the existing embryos to try to “correct” the defective gene instead of trying to “select” a normal embryo. These technologies are still in the early stages of development and are remotely distant from clinical applications. On the other hand, although germline gene editing, if actualized, would be a monumental breakthrough in the history of genetics and medicine, we must be cognizant of its serious legal, societal, and ethical ramifications, which are currently unknown. Furthermore, even at the biologic and technical level, the technology still is not advanced enough to reliably rule out off-target modifications, and the unintended clinical consequences of the on-target corrections have not been studied either.

Regulation of genetic modifications

Due to these myriad concerns and the lack of an existing appropriate regulatory framework and oversight for such interventions, current US law (since December 2015, through provisions in annual federal appropriations laws passed by Congress and renewed annually thereafter) bars the US Food and Drug Administration from considering any clinical trial application “in which a human embryo is intentionally created or modified to include a heritable genetic modification.” Notably, this moratorium also prohibits mitochondrial replacement technology (MRT), which is a less controversial and relatively better-studied innovation.

Mitochondrial genetic disorders caused by the mutations in mitochondrial DNA (versus nuclear DNA) are amenable to a specific treatment strategy aimed at substituting the defective maternal mitochondrial genome with the mitochondrial genome of an unaffected donor oocyte. This can be achieved via either pronuclear transfer, which involves isolation and transfer of the male and female pronuclei from an affected embryo to an enucleated normal donor embryo, or maternal spindle transfer, which involves isolation and transfer of the metaphase II spindle complex of an affected oocyte to an enucleated disease-free donor egg. It is noteworthy that in 2015 in the United Kingdom, Parliament expanded the definition of “permitted eggs and embryos” to include those “where unhealthy mitochondrial DNA is replaced by healthy mitochondrial DNA from a donor.” This thereby allows the UK Human Fertilisation and Embryology Authority to formally direct and oversee clinical trials in MRT.

Summing up

Although the future of assisted human reproduction cannot be clearly outlined at this time, it is likely to be radically different from the current state given these emerging applications at the intersection of ART and diagnostic and therapeutic genetics. To ensure that exploring this uncharted territory will ultimately be in the interest of humankind and civilization, proper regulatory oversight—after careful consideration of all ethical, societal, and legal implications—needs to be developed for all preclinical and clinical research in this field. Participatory public engagement must be an integrated part of this process. ●