OBG Management

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●

ILLUSTRATION BY KIMBERLY MARTENS FOR OBG MANAGEMENT

CASE Part 1: CPR initiated during induction of labor

A 32-year-old gravida 4 para 3-0-0-3 is undergoing induction of labor with intravenous (IV) oxytocin at 39 weeks of gestation. She has no significant medical or obstetric history. Fifteen minutes after reaching complete cervical dilation, she says “I don’t feel right,” then suddenly loses consciousness. The nurse finds no detectable pulse, calls a “code blue,” and initiates cardiopulmonary resuscitation (CPR). The obstetrician is notified, appears promptly, assesses the situation, and delivers a 3.6-kg baby via vacuum extraction. Apgar score is 2/10 at 1 minute and 6/10 at 5 minutes. After delivery of the placenta, there is uterine atony and brisk hemorrhage with 2 L of blood loss.

Management of AFE: A rare complication

This case demonstrates a classic presentation of amniotic fluid embolism (AFE) syndrome—a patient in labor or within 30 minutes after delivery has sudden onset of cardiorespiratory collapse followed by disseminated intravascular coagulation (DIC). AFE is rare, affecting only about 2 to 6 per 100,000 births, but classic cases have a reported maternal mortality rate that exceeds 50%.¹ It is thought to reflect a complex, systemic proinflammatory response to maternal intravasation of pregnancy material, such as trophoblast, thromboplastins, fetal cells, or amniotic fluid. Because the syndrome is not necessarily directly caused by emboli or by amniotic fluid per se,² it has been proposed that AFE be called “anaphylactoid syndrome of pregnancy,” but this terminology has not yet been widely adopted.³

Guidelines from the Society for Maternal-Fetal Medicine (SMFM) recommend several time-critical steps for the initial stabilization and management of patients with AFE.⁴ However, because AFE is rare, most obstetric providers may not encounter a case for many years or even decades after they have received training, so it is unrealistic to expect that they will remember these guidelines when they are needed. For this reason, when AFE occurs, it is important to have a readily accessible cognitive aid, such as a checklist that summarizes the key management steps. The SMFM provides a checklist for initial management of AFE that can be used at your institution; it is presented in the FIGURE and provides the outline for this discussion.⁵

Provide CPR immediately

Most AFE cases are accompanied by cardiorespiratory arrest. If the patient has no pulse, call a “code” to mobilize additional help and immediately start CPR. Use a backboard to make cardiac compressions most effective and manually displace the uterus or tilt the patient to avoid supine hypotension. Designate a timekeeper to call out 1-minute intervals and record critical data, such as medication administration and laboratory orders/results.

Expedite delivery

Immediate delivery is needed if maternal cardiac activity is not restored within 4 minutes of starting CPR, with a target to have delivery completed within 5 minutes. Operative vaginal delivery may be an option if delivery is imminent, as in the case presented, but cesarean delivery (CD) will be needed in most cases. This was previously called “perimortem cesarean” delivery, but the term “resuscitative hysterotomy” has been proposed because the primary goal is to improve the effectiveness of CPR⁶ and prevent both maternal and perinatal death. CPR is less effective in pregnant women because the pregnant uterus takes a substantial fraction of the maternal cardiac output, as well as compresses the vena cava. Some experts suggest that, rather than waiting 4 minutes, CD should be started as soon as an obstetrician or other surgeon is present, unless there is an immediate response to electrical cardioversion.^6,7

In most cases, immediate CD should be performed wherever the patient is located rather than using precious minutes to move the patient to an operating room. Antiseptic preparation is expedited by simply pouring povidone-iodine or chlorhexidine over the lower abdomen if readily available; if not available, skip this step. Enter the abdomen and uterus as rapidly as possible using only a scalpel to make generous midline incisions.

If CPR is not required, proceed with cesarean or operative vaginal delivery as soon as the mother has been stabilized. These procedures should be performed using standard safety precautions outlined in the SMFM patient safety checklists for cesarean or operative vaginal delivery.^8,9

Continue to: Anticipate hemorrhage...

Be prepared for uterine atony, coagulopathy, and catastrophic hemorrhage. Initiate IV oxytocin prophylaxis as soon as the infant is delivered. Have a low threshold for giving other uterotonic agents such as methylergonovine, carboprost, or misoprostol. If hemorrhage or DIC occurs, give tranexamic acid. Have the anesthesiologist or trauma team (if available) insert an intraosseous line for fluid resuscitation if peripheral IV access is inadequate.

Massive transfusion is often needed to treat DIC, which occurs in most AFE cases. Anticipate—do not wait—for DIC to occur. We propose activating your hospital’s massive transfusion protocol (MTP) as soon as you diagnose AFE so that blood products will be available as soon as possible. A typical MTP provides several units of red blood cells, a pheresis pack of platelets, and fresh/frozen plasma (FFP). If clinically indicated, administer cryoprecipitate instead of FFP to minimize volume overload, which may occur with FFP.

CASE Part 2: MTP initiated to treat DIC

The MTP is initiated. Laboratory results immediately pre-transfusion include hemoglobin 11.3 g/dL, platelet count 46,000 per mm³, fibrinogen 87 mg/dL, and an elevated prothrombin time international normalized ratio.

Expect heart failure

The initial hemodynamic picture in AFE is right heart failure, which should optimally be managed by a specialist from anesthesiology, cardiology, or critical care as soon as they are available. An emergency department physician may manage the hemodynamics until a specialist arrives. Avoidance of fluid overload is one important principle. If fluid challenges are needed for hypovolemic shock, boluses should be restricted to 500 mL rather than the traditional 1000 mL.

Pharmacologic treatment may include vasopressors, inotropic agents, and pulmonary vasodilators. Example medications and dosages recommended by SMFM are summarized in the checklist (FIGURE).⁵

After the initial phase of recovery, the hemodynamic picture often changes from right heart failure to left heart failure. Management of left heart failure is not covered in the SMFM checklist because, by the time it appears, the patient will usually be in the intensive care unit, managed by the critical care team. Management of left heart failure generally includes diuresis as needed for cardiogenic pulmonary edema, optimization of cardiac preload, and inotropic agents or vasopressors if needed to maintain cardiac output or perfusion pressure.⁴

Debrief, learning opportunities

Complex emergencies such as AFE are rarely handled 100% perfectly, even those with a good outcome, so they present opportunities for team learning and improvement. The team should conduct a 10- to 15-minute debrief soon after the patient is stabilized. Make an explicit statement that the main goal of the debrief is to gather suggestions as to how systems and processes could be improved for next time, not to find fault or lay blame on individuals. Encourage all personnel involved in the initial management to attend and discuss what went well and what did not. Another goal is to provide support for individuals who may feel traumatized by the dramatic, frightening events surrounding an AFE and by the poor patient outcome or guarded prognosis that frequently follows. Another goal is to discuss the plan for providing support and disclosure to the patient and family.

The vast majority of AFE cases meet criteria to be designated as “sentinel events,” because of patient transfer to the intensive care unit, multi-unit blood transfusion, other severe maternal morbidities, or maternal death. Therefore, most AFE cases will trigger a root cause analysis (RCA) or other formal sentinel event analysis conducted by the hospital’s Safety or Quality Department. As with the immediate post-event debrief, the first goal of the RCA is to identify systems issues that may have resulted in suboptimal care and that can be modified to improve future care. Specific issues regarding the checklist should also be addressed:

• Was the checklist used?
• Was the checklist available?
• Are there items on the checklist that need to be modified, added, or deleted?

The RCA concludes with the development of a performance improvement plan.

Ultimately, we encourage all AFE cases be reported to the registry maintained by the Amniotic Fluid Embolism Foundation at https://www.afesupport.org/, regardless of whether the outcome was favorable for the mother and newborn. The registry includes over 130 AFE cases since 2013 from around the world. Researchers periodically report on the registry findings.¹⁰ If providers report cases with both good and bad outcomes, the registry may provide future insights regarding which adjunctive or empiric treatments may or may not be promising.

Continue to: Empiric treatments...

From time-to-time, new regimens for empiric treatment of AFE are reported. It is important to recognize that these reports are generally uncontrolled case reports of favorable outcomes and that, without a control group, it is impossible to determine to what extent the treatment contributed to the outcome or was merely incidental. Given the rarity of AFE, it seems unlikely that there will ever be a randomized clinical trial or even a controlled prospective study comparing treatment regimens.

The “A-OK” regimen is an empiric treatment that has garnered some interest after an initial case report.¹¹ It consists of an anticholinergic agent (atropine 0.2 mg IV), a selective 5-HT3 receptor antagonist (ondansetron 8 mg IV), and a nonsteroidal anti-inflammatory drug (ketorolac 15 mg IV). We have some reservations about this regimen, however, because atropine is relatively contraindicated if the patient has tachycardia (which is common in patients with hemorrhage) and ketorolac may suppress platelet function, which might be harmful for patients with DIC or thrombocytopenia.

Another empiric treatment is the “50-50-500” regimen, which includes an H1 antihistamine (diphenhydramine 50 mg IV), an H2 antihistamine (famotidine 50 mg IV), and a corticosteroid (hydrocortisone 500 mg IV). This regimen aims to suppress histamine-mediated and cell-mediated inflammatory responses, based on the notion that proinflammatory responses likely mediate much of the underlying pathophysiology of the AFE syndrome.

We would emphasize that these empiric regimens are not clinically validated, US Food and Drug Administration approved for treatment of AFE, or considered standard of care. Future reports of these and other regimens will be needed to evaluate their efficacy, limitations, and risks. Again, we encourage providers to report all AFE cases to the AFE Foundation registry, regardless of whether the treatments are successful.

CASE Conclusion

The hemorrhage stops after administration of oxytocin, carboprost, 6 units of cryoprecipitate, and a 6-unit platelet pheresis pack. The patient is transferred to the intensive care unit where she eventually requires a total of 10 units of red cells, 8 more units of cryoprecipitate, and another platelet pheresis pack. She is discharged to home in stable condition on postpartum day 4.

Be prepared, have the checklist ready

Because AFE is rare, most members of the health care team will have no prior experience managing a real case. It may have been years or decades since they had any education on AFE or they last read a review article such as this one. It is even possible the anesthesiologist, cardiologist, or critical care specialist has never heard of AFE. Thus if they rely on memory alone, there is substantial risk of forgetting items, getting dosages wrong, or other errors. With this in mind, what is the best way to prepare the team to expeditiously employ the management steps outlined here?

Use of a checklist that summarizes these key steps for early management, such as the SMFM checklist in the FIGURE, will help ensure that all relevant steps are performed in every AFE case. It is designed to be printed on a single sheet of letter-sized paper, and we propose that every labor and delivery (L&D) unit keep laminated copies of this checklist in several places where they will be immediately available should an AFE occur. Copies can be kept on the anesthesia carts in the L&D operating rooms, in an emergency procedures binder on the unit, and on the “crash carts” and hemorrhage supply carts in the L&D unit. Effective implementation of an AFE checklist requires all personnel know where to readily find it and have some familiarity with its contents.

An interdisciplinary team comprising representatives from nursing, obstetrics, and anesthesia should meet to discuss whether the checklist needs to be modified to fit the local hospital formulary or other unique local circumstances. The team should develop an implementation plan that includes where to keep checklist copies, a process to periodically ensure that the copies are still present and readable, a roll-out plan to inform all personnel about the checklist process, and most importantly a training plan that includes incorporating AFE cases into the schedule of multidisciplinary simulations and drills for obstetric emergencies. Other implementation strategies are outlined in the SMFM document.⁵

Ultimately an organized, systematic approach is recommended for management of AFE. There is no single best treatment of AFE; it is supportive and directed toward the underlying pathophysiology, which may vary from patient to patient. Therefore, although a checklist, in conjunction with regular education and simulation activities, may help optimize care and improve outcomes, there is still a high risk of maternal morbidity and mortality from AFE. ●

“[Operative vaginal delivery] was used in only 3% of all US births in 2013, a shift from approximately 30% in 1987,” reported Hayley M. Miller, MD, and Danielle M. Panelli, MD, in the June issue of OBG Management. In their article, “How are maternal and neonatal outcomes impacted by the contemporary practice of operative vaginal delivery [OVD],” the authors mentioned that level of experience by the operator can bias reported complication rates of OVD. Although they examined evidence that found the absolute risk of neonatal trauma to be low following OVD, perineal lacerations “appeared to remain a major driver of maternal morbidity….” Given the current infrequency of OVD, they urged that training be prioritized so OVD can be offered as a safe alternative to cesarean delivery. OBG Management followed up with a poll for readers to ask, “Are you comfortable performing OVD as an alternative to cesarean?”

“[Operative vaginal delivery] was used in only 3% of all US births in 2013, a shift from approximately 30% in 1987,” reported Hayley M. Miller, MD, and Danielle M. Panelli, MD, in the June issue of OBG Management. In their article, “How are maternal and neonatal outcomes impacted by the contemporary practice of operative vaginal delivery [OVD],” the authors mentioned that level of experience by the operator can bias reported complication rates of OVD. Although they examined evidence that found the absolute risk of neonatal trauma to be low following OVD, perineal lacerations “appeared to remain a major driver of maternal morbidity….” Given the current infrequency of OVD, they urged that training be prioritized so OVD can be offered as a safe alternative to cesarean delivery. OBG Management followed up with a poll for readers to ask, “Are you comfortable performing OVD as an alternative to cesarean?”

“[Operative vaginal delivery] was used in only 3% of all US births in 2013, a shift from approximately 30% in 1987,” reported Hayley M. Miller, MD, and Danielle M. Panelli, MD, in the June issue of OBG Management. In their article, “How are maternal and neonatal outcomes impacted by the contemporary practice of operative vaginal delivery [OVD],” the authors mentioned that level of experience by the operator can bias reported complication rates of OVD. Although they examined evidence that found the absolute risk of neonatal trauma to be low following OVD, perineal lacerations “appeared to remain a major driver of maternal morbidity….” Given the current infrequency of OVD, they urged that training be prioritized so OVD can be offered as a safe alternative to cesarean delivery. OBG Management followed up with a poll for readers to ask, “Are you comfortable performing OVD as an alternative to cesarean?”

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[polldaddy:11135441]

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Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

Last year, our Update focused on the expansion of sequencing in prenatal diagnosis. This year, we are taking a step sideways to remember the many diagnoses we may miss if we rely on exome sequencing alone. A recent case report in Prenatal Diagnosis describes a pregnancy affected by fetal akinesia sequence and polyhydramnios in which sequencing did not reveal a diagnosis. Expansion of the differential to include congenital myotonic dystrophy and subsequent triplet repeat testing led the clinicians to the diagnosis and identification of a triplet repeat expansion in the DMPK gene. This case serves as our first example of how complementary testing and technologies should continue to help us make critical diagnoses. 

What is the yield of exome sequencing vs panels in nonimmune hydrops?

Rogers R, Moyer K, Moise KJ Jr. Congenital myotonic dystrophy: an overlooked diagnosis not amenable to detection by sequencing. Prenat Diagn. 2022;42:233-235. doi:10.1002/pd.6105.

Norton ME, Ziffle JV, Lianoglou BR, et al. Exome sequencing vs targeted gene panels for the evaluation of nonimmune hydrops fetalis. Am J Obstet Gynecol. 2021;28:S0002-9378(21)00828-0. doi:10.1016/j.ajog.2021.07.014.
 

We have had several illuminating discussions with our colleagues about the merits of exome sequencing (ES) versus panels and other modalities for fetal diagnosis. Many obstetricians practicing at the leading edge may feel like ES should be utilized uniformly for fetal anomalies with nondiagnostic karyotype or microarray. However, for well-defined phenotypes with clear and narrow lists of implicated genes (eg, skeletal dysplasias) or patients without insurance coverage, panel sequencing still has utility in prenatal diagnosis. The question of which phenotypes most benefit from ES versus panel sequencing is an area of interesting, ongoing research for several investigators.

Secondary analysis of nonimmune hydrops cohort

Norton and colleagues tackled one such cohort in a study presented in the American Journal of Obstetrics and Gynecology. They compared the proportion of diagnoses that would have been identified in commercial lab panels with their research of phenotype-driven ES in a cohort of 127 fetuses with features of nonimmune hydrops fetalis (NIHF). NIHF can be caused by a variety of single-gene disorders in addition to chromosomal disorders and copy number variants on chromosomal microarray. Patients were eligible for inclusion in the cohort if they had a nondiagnostic karyotype or microarray and any of the following features: nuchal translucency of 3.5 mm or greater, cystic hygroma, pleural effusion, pericardial effusion, ascites, or skin edema. Standard sequencing methods and variant analysis were performed. They assumed 100% analytical sensitivity and specificity of the panels for variant detection and collected cost information on the targeted gene panels.

Study outcomes

In the ES analysis of cases, 37 of 127 cases (29%) had a pathogenic or likely pathogenic variant in 1 of 29 genes, and another 12 of 127 cases (9%) had variants of uncertain significance that were strongly suspected to be the etiology during clinical analysis. The types of disorders that were identified are listed in the TABLE. In addition to a feature of NIHF, 50% of the cases had a structural anomaly.

There were 10 identified clinical panels from 7 clinical laboratories. These panels ranged in size from 11 to 128 genes. The highest simulated yield of any commercial panel was only 62% of the pathogenic variants identified by ES. The other commercial laboratory panels detection yield ranged from 11% to 62% of pathogenic variants detected by ES. For overall yield, the largest panel would have a diagnostic yield of 18% of diagnoses relative to the 29% diagnostic yield from ES.

The largest panel included 128 genes prior to the publication of the original cohort and was updated after publication to include 148 genes. The larger updated panel would have identified all of the patients in the ES cohort. However, many of the other panels listed would have identified a smaller fraction of the variants identified by ES (range, 11%-62%). At the time of publication, the cost of the panels ranged from $640 to $3,500, and the cost of prenatal ES ranged from $2,458 to $7,500.

Continue to: Strengths and limitations...

Strengths and limitations

Twenty-three percent of the patients who were sequenced had an increased fetal nuchal translucency or cystic hygroma, and another 17% had a single fetal effusion. This inclusivity makes this study more applicable to broader fetal anomaly populations. However, it is worth noting that only 61% of patients had NIHF by the definition of 2 or more fluid collections or skin thickening.

The authors assumed 100% sensitivity and specificity for the panel tests relative to diagnostic ES results, but this may not reflect real-life analysis. There is inherent subjectivity and subsequent differences in variant calling (deciding which genetic changes are pathogenic) between institutions and companies despite efforts to standardize this process. Due to the simulated nature of this study, these differences are not captured. Additionally, although the authors note that the research ES had at least 30 times the coverage (an adequate number of sequence reads for accurate testing) than did the commercial lab panels, some gene panels have additional sequencing of intronic regions, copy number analysis, and up to 10 times more coverage than ES, which could lead to more diagnoses.

Frequency of Beckwith-Widemann syndrome in prenatally diagnosed omphaloceles

Abbasi N, Moore A, Chiu P, et al. Prenatally diagnosed omphaloceles: report of 92 cases and association with Beckwith-Wiedemann syndrome. Prenat Diagn. 2021;41:798-816. doi:10.1002/pd.5930.

An omphalocele is diagnosed prenatally on ultrasound when an anterior midline mass, often containing abdominal contents, is seen herniating into the base of the umbilical cord. Omphaloceles are often associated with additional structural abnormalities and underlying genetic syndromes, thus a thorough fetal assessment is required for accurate prenatal counseling and neonatal care.

Identification of Beckwith-Widemann syndrome (BWS) in the setting of a prenatally diagnosed omphalocele is difficult because of its wide range of clinical features and its unique genetic basis. Unlike many genetic disorders that are caused by specific genetic variants, or spelling changes in the genes, BWS results from a change in the expression of one or more of the genes in a specific region of chromosome 11. A high index of clinical suspicion as well as an understanding of the various genetic and epigenetics alterations that cause BWS is required for prenatal diagnosis.

Retrospective cohort at a single center

The authors in this study reviewed all pregnancies in which an omphalocele was diagnosed prenatally at a single center between 2010 and 2015. They describe a standard prenatal evaluation following identification of an omphalocele including echocardiogram, detailed anatomic survey, and availability of an amniocentesis to facilitate aneuploidy screening and testing for BWS. This review also includes an overview of perinatal and long-term outcomes for cases of BWS diagnosed at their center between 2000 and 2015.

Study outcomes

Results of prenatal genetic testing in this cohort were divided between cases of an isolated omphalocele (without other structural changes) and cases of nonisolated omphaloceles. In the group of pregnancies with an isolated omphalocele, 2 of 27 pregnancies (7.4%) were found to have an abnormal karyotype, and 6 of 16 of the remaining pregnancies (37.5%) were diagnosed with BWS. Among the group of pregnancies with a nonisolated omphalocele, 23 of 59 pregnancies (39%) were found to have an abnormal karyotype, and 1 of 20 pregnancies (5%) were diagnosed with BWS.

Prenatal sonographic features associated with cases of BWS included polyhydramnios in 12 of 19 cases (63%) and macrosomia in 8 of 19 cases (42%). Macroglossia is another characteristic feature of the disorder, which was identified in 4 of 19 cases (21%) prenatally and in an additional 10 of 19 cases (52.6%) postnatally. Interestingly, only 1 of the cases of BWS was caused by a microdeletion at 11p15.4—a change that was identified on microarray. The additional 6 cases of BWS were caused by imprinting changes in the region, which are only detectable with a specific methylation-analysis technique.

Among the 19 cases of BWS identified over a 15-year period, there was 1 intrauterine demise. Preterm birth occurred in 10 of 19 cases (52.6%), including 8 of 19 cases (42.1%) of spontaneous preterm labor. Respiratory distress (27.8%), hypoglycemia (61%), and gastrointestinal reflux (59%) were common neonatal complications. Embryonal tumors were diagnosed in 2 of 16 patients (12.5%). Although neurodevelopmental outcomes were incomplete, their data suggested normal development in 75% of children. There were 2 neonatal deaths in this cohort and 1 childhood death at age 2 years.

Study strengths and limitations

As with many studies investigating a rare disorder, this study is limited by its retrospective nature and small sample size. Nevertheless, it adds an important cohort of patients with a prenatally diagnosed omphalocele to the literature and illuminates the utility of a standardized approach to testing for BWS in this population.

Continue to: Genetic diagnoses that could have been identified by expanded carrier screening...

Stevens BK, Nunley PB, Wagner C, et al. Utility of expanded carrier screening in pregnancies with ultrasound abnormalities. Prenat Diagn. 2022;42:60-78. doi:10.1002/pd.6069.

This series is a thorough retrospective review of patients evaluated in a pediatric genetics clinic from 2014 through 2017. Patients were included if they were evaluated in the first 6 months of life and had a structural abnormality that might be detected on prenatal ultrasonography. The genetic testing results were analyzed and categorized according to types of genetic disorders, with the goal of identifying how many patients might have been identified by expanded carrier screening (ECS) panels.

Study outcomes

A total of 931 charts were reviewed, and 85% (791 of 931) of patients evaluated in the first 6 months of life were determined to have a structural anomaly that might be detected on prenatal ultrasonography. Of those patients, 691 went on to have genetic testing and 32.1% (222 of 691) of them had a diagnostic (pathogenic) genetic testing result related to the phenotype. The types of diagnostic testing results are shown in the FIGURE. Notably, 42 single-gene disorders were detected.

FIGURE Diagnostic test result in pediatric patients evaluated under age 6 months

Of those 222 patients with diagnostic results, there were 8 patients with autosomal recessive and X-linked conditions that could be detected using a 500-gene ECS panel. Five patients could be detected with a 271-gene panel. After nondiagnostic microarray, 11.3% of patients had a condition that could be detected by using a 500-gene ECS panel. The identified conditions included cystic fibrosis, CYP21‐related congenital adrenal hyperplasia, autosomal recessive polycystic kidney disease, Antley‐Bixler syndrome, and Morquio syndrome type A.

Furthermore, the authors conducted a literature review of 271 conditions and found that 32% (88 of 271) of conditions may be associated with ultrasound findings.

Study strengths and limitations

When applying these data to prenatal populations, the authors acknowledge several notable limitations. There is a selection bias toward less-severe phenotypes for many patients choosing to continue rather than to interrupt a pregnancy. Additionally, only 23% of the patients in the study had a microarray and ES, which may lead to an underrepresentation of single-gene disorders and an underestimation of the utility of ECS. Finally, a retrospective classification of structural abnormalities that may be detectable by ultrasonography may not always reflect what is actually reported in prenatal imaging.

However, the work that the authors put forth to evaluate and categorize 931 participants by the results of genetic testing and structural anomalies is appreciated, and the level of detail is impressive for this retrospective chart review. Additionally, the tables itemizing the authors’ review of 271 ECS disorders that may have ultrasonography findings categorized by disorder and system are helpful and quick diagnostic references for clinicians providing prenatal care. ●

Obstetrics and gynecology (ObGyn) is a surgical specialty, yet the training of ObGyn residents differs significantly from that of residents in other surgical specialties. In addition to attaining competency in both the distinct but related fields of obstetrics and gynecology, ObGyn residents have their training condensed into 4 years rather than the 5 years’ training of many other surgical specialties. This limits the time dedicated to gynecologic surgery, currently 18 to 20 months in most programs, and has been exacerbated by tighter duty-hour restrictions.¹

Additionally, with increasing demand for minimally invasive procedures, residents are expected to attain competency in a growing breadth of gynecologic procedures in a patient population with increasing morbidity, and they may have less autonomy to do so in an increasingly litigious environment.² Furthermore, annual hysterectomy cases are declining, from about 680,000 in 2002 to 430,000 in 2010,³ and these declining rates are seen in the low case numbers of recent graduates.⁴

Training time, procedure complexity

With less time to master a growing body of increasingly complex procedures, is the profession adequately training gynecologic surgeons? Many gynecologic surgeons are concerned that the answer is no and that significant shifts in resident training are needed to generate safe and competent gynecologic surgeons. These training deficits represent a deficiency in the quality of care for women specifically, and thus the inattention to training gynecologic surgeons should be considered a health care disparity.

The concern over insufficient attention to gynecologic surgical training is not new, nor are proposed solutions, with many physicians citing the above concerns.^5-9 In 2018, the Accreditation Council for Graduate Medical Education (ACGME) case minimums for hysterectomy increased to 85 from 70 hysterectomies, with a shift toward minimally invasive hysterectomy.¹⁰ Otherwise, minimal national changes have been made in this century to training gynecologic surgeons.

Tracking as an option

Many critics of current ObGyn training argue that obstetrics and gynecology, while related, have significantly different pathologies, surgical approaches, and skill sets and thus warrant the option to track toward obstetrics or gynecology after attaining limited core skill set in residency. In 2010, the Carnegie Foundation for the Advancement of Teaching called for the need for increased individualization opportunities in graduate medical education, citing that minimal changes have been made to medical education since the Flexner Report a century prior.¹¹

Notably, tracking has been implemented with success at Cleveland Clinic, where residents are given 5 to 10 weeks of time allotted to their specific fields of interest, while still meeting minimum ACGME requirements and, in some cases, exceeding hysterectomy minimums by as much as 500%.¹² Tracking is viewed positively by a majority of program directors.¹³ See the box below for Dr. Ferrando’s experience on tracking at the Cleveland Clinic.

Simulation training

Other educators advocate for maximizing preparedness for the operating room by using high-fidelity simulation.^14,15 Simulation allows for the acquisition of basic technical skills needed for surgery as well as for repetition not easily achieved in the current surgical environment. Additionally, it provides lower-level learners the opportunity to acquire basic skills in a safe setting, thereby enhancing the ability to participate meaningfully on arrival in the operating room.¹⁶

In 2018, the American Board of Obstetrics and Gynecology added the Fundamentals of Laparoscopic Surgery certification as a new requirement for board certification.¹⁷ Laparoscopic and robotic surgery simulators allow trainees to develop coordination and specific skills, like knot tying and suturing. Additionally, models are available with varying levels of fidelity for vaginal and abdominal hysterectomy.^18-20 See the box below for Dr. Miyazaki’s experience in developing the Miya Model trainer for vaginal surgery simulation.

Structured feedback

Finally, if a resident has limited exposure to a specific procedure, maximizing the preparation and feedback for each procedure is paramount. However, surgeons receive minimal formal training in teaching trainees, which leads to inconsistent and underutilized feedback.²¹ Specific structured feedback models have been implemented with success in the general surgery literature, including the SHARP (Set learning objectives, How did it go, Address concerns, Review learning points, Plan ahead) and BID (Briefing, Intraoperative, Debriefing) models.^22,23

Reimbursement reform

While surgical reimbursement is not directly tied to resident education, decreased reimbursement to women’s health pathology and procedures has the downstream effect of decreasing the funds available for ObGyn departments to invest in research and education. Additionally, “suboptimal mastery or maintenance of appropriate surgical skills results in procedural inefficiencies that compound surgical cost.”⁵ Providers and payors alike should therefore be motivated to improve funding in order to improve adequate training of gynecologic surgeons. Payment reform is necessary to equally value women’s health procedures but also can ensure that gynecologic surgeons have the funds needed to train a competent next generation of ObGyn physicians. ●

Obstetrics and gynecology (ObGyn) is a surgical specialty, yet the training of ObGyn residents differs significantly from that of residents in other surgical specialties. In addition to attaining competency in both the distinct but related fields of obstetrics and gynecology, ObGyn residents have their training condensed into 4 years rather than the 5 years’ training of many other surgical specialties. This limits the time dedicated to gynecologic surgery, currently 18 to 20 months in most programs, and has been exacerbated by tighter duty-hour restrictions.¹

Additionally, with increasing demand for minimally invasive procedures, residents are expected to attain competency in a growing breadth of gynecologic procedures in a patient population with increasing morbidity, and they may have less autonomy to do so in an increasingly litigious environment.² Furthermore, annual hysterectomy cases are declining, from about 680,000 in 2002 to 430,000 in 2010,³ and these declining rates are seen in the low case numbers of recent graduates.⁴

Training time, procedure complexity

With less time to master a growing body of increasingly complex procedures, is the profession adequately training gynecologic surgeons? Many gynecologic surgeons are concerned that the answer is no and that significant shifts in resident training are needed to generate safe and competent gynecologic surgeons. These training deficits represent a deficiency in the quality of care for women specifically, and thus the inattention to training gynecologic surgeons should be considered a health care disparity.

The concern over insufficient attention to gynecologic surgical training is not new, nor are proposed solutions, with many physicians citing the above concerns.^5-9 In 2018, the Accreditation Council for Graduate Medical Education (ACGME) case minimums for hysterectomy increased to 85 from 70 hysterectomies, with a shift toward minimally invasive hysterectomy.¹⁰ Otherwise, minimal national changes have been made in this century to training gynecologic surgeons.

Tracking as an option

Many critics of current ObGyn training argue that obstetrics and gynecology, while related, have significantly different pathologies, surgical approaches, and skill sets and thus warrant the option to track toward obstetrics or gynecology after attaining limited core skill set in residency. In 2010, the Carnegie Foundation for the Advancement of Teaching called for the need for increased individualization opportunities in graduate medical education, citing that minimal changes have been made to medical education since the Flexner Report a century prior.¹¹

Notably, tracking has been implemented with success at Cleveland Clinic, where residents are given 5 to 10 weeks of time allotted to their specific fields of interest, while still meeting minimum ACGME requirements and, in some cases, exceeding hysterectomy minimums by as much as 500%.¹² Tracking is viewed positively by a majority of program directors.¹³ See the box below for Dr. Ferrando’s experience on tracking at the Cleveland Clinic.

Simulation training

Other educators advocate for maximizing preparedness for the operating room by using high-fidelity simulation.^14,15 Simulation allows for the acquisition of basic technical skills needed for surgery as well as for repetition not easily achieved in the current surgical environment. Additionally, it provides lower-level learners the opportunity to acquire basic skills in a safe setting, thereby enhancing the ability to participate meaningfully on arrival in the operating room.¹⁶

In 2018, the American Board of Obstetrics and Gynecology added the Fundamentals of Laparoscopic Surgery certification as a new requirement for board certification.¹⁷ Laparoscopic and robotic surgery simulators allow trainees to develop coordination and specific skills, like knot tying and suturing. Additionally, models are available with varying levels of fidelity for vaginal and abdominal hysterectomy.^18-20 See the box below for Dr. Miyazaki’s experience in developing the Miya Model trainer for vaginal surgery simulation.

Structured feedback

Finally, if a resident has limited exposure to a specific procedure, maximizing the preparation and feedback for each procedure is paramount. However, surgeons receive minimal formal training in teaching trainees, which leads to inconsistent and underutilized feedback.²¹ Specific structured feedback models have been implemented with success in the general surgery literature, including the SHARP (Set learning objectives, How did it go, Address concerns, Review learning points, Plan ahead) and BID (Briefing, Intraoperative, Debriefing) models.^22,23

Reimbursement reform

While surgical reimbursement is not directly tied to resident education, decreased reimbursement to women’s health pathology and procedures has the downstream effect of decreasing the funds available for ObGyn departments to invest in research and education. Additionally, “suboptimal mastery or maintenance of appropriate surgical skills results in procedural inefficiencies that compound surgical cost.”⁵ Providers and payors alike should therefore be motivated to improve funding in order to improve adequate training of gynecologic surgeons. Payment reform is necessary to equally value women’s health procedures but also can ensure that gynecologic surgeons have the funds needed to train a competent next generation of ObGyn physicians. ●

Obstetrics and gynecology (ObGyn) is a surgical specialty, yet the training of ObGyn residents differs significantly from that of residents in other surgical specialties. In addition to attaining competency in both the distinct but related fields of obstetrics and gynecology, ObGyn residents have their training condensed into 4 years rather than the 5 years’ training of many other surgical specialties. This limits the time dedicated to gynecologic surgery, currently 18 to 20 months in most programs, and has been exacerbated by tighter duty-hour restrictions.¹

Additionally, with increasing demand for minimally invasive procedures, residents are expected to attain competency in a growing breadth of gynecologic procedures in a patient population with increasing morbidity, and they may have less autonomy to do so in an increasingly litigious environment.² Furthermore, annual hysterectomy cases are declining, from about 680,000 in 2002 to 430,000 in 2010,³ and these declining rates are seen in the low case numbers of recent graduates.⁴

Training time, procedure complexity

With less time to master a growing body of increasingly complex procedures, is the profession adequately training gynecologic surgeons? Many gynecologic surgeons are concerned that the answer is no and that significant shifts in resident training are needed to generate safe and competent gynecologic surgeons. These training deficits represent a deficiency in the quality of care for women specifically, and thus the inattention to training gynecologic surgeons should be considered a health care disparity.

The concern over insufficient attention to gynecologic surgical training is not new, nor are proposed solutions, with many physicians citing the above concerns.^5-9 In 2018, the Accreditation Council for Graduate Medical Education (ACGME) case minimums for hysterectomy increased to 85 from 70 hysterectomies, with a shift toward minimally invasive hysterectomy.¹⁰ Otherwise, minimal national changes have been made in this century to training gynecologic surgeons.

Tracking as an option

Many critics of current ObGyn training argue that obstetrics and gynecology, while related, have significantly different pathologies, surgical approaches, and skill sets and thus warrant the option to track toward obstetrics or gynecology after attaining limited core skill set in residency. In 2010, the Carnegie Foundation for the Advancement of Teaching called for the need for increased individualization opportunities in graduate medical education, citing that minimal changes have been made to medical education since the Flexner Report a century prior.¹¹

Notably, tracking has been implemented with success at Cleveland Clinic, where residents are given 5 to 10 weeks of time allotted to their specific fields of interest, while still meeting minimum ACGME requirements and, in some cases, exceeding hysterectomy minimums by as much as 500%.¹² Tracking is viewed positively by a majority of program directors.¹³ See the box below for Dr. Ferrando’s experience on tracking at the Cleveland Clinic.

Simulation training

Other educators advocate for maximizing preparedness for the operating room by using high-fidelity simulation.^14,15 Simulation allows for the acquisition of basic technical skills needed for surgery as well as for repetition not easily achieved in the current surgical environment. Additionally, it provides lower-level learners the opportunity to acquire basic skills in a safe setting, thereby enhancing the ability to participate meaningfully on arrival in the operating room.¹⁶

In 2018, the American Board of Obstetrics and Gynecology added the Fundamentals of Laparoscopic Surgery certification as a new requirement for board certification.¹⁷ Laparoscopic and robotic surgery simulators allow trainees to develop coordination and specific skills, like knot tying and suturing. Additionally, models are available with varying levels of fidelity for vaginal and abdominal hysterectomy.^18-20 See the box below for Dr. Miyazaki’s experience in developing the Miya Model trainer for vaginal surgery simulation.

Structured feedback

Finally, if a resident has limited exposure to a specific procedure, maximizing the preparation and feedback for each procedure is paramount. However, surgeons receive minimal formal training in teaching trainees, which leads to inconsistent and underutilized feedback.²¹ Specific structured feedback models have been implemented with success in the general surgery literature, including the SHARP (Set learning objectives, How did it go, Address concerns, Review learning points, Plan ahead) and BID (Briefing, Intraoperative, Debriefing) models.^22,23

Reimbursement reform

While surgical reimbursement is not directly tied to resident education, decreased reimbursement to women’s health pathology and procedures has the downstream effect of decreasing the funds available for ObGyn departments to invest in research and education. Additionally, “suboptimal mastery or maintenance of appropriate surgical skills results in procedural inefficiencies that compound surgical cost.”⁵ Providers and payors alike should therefore be motivated to improve funding in order to improve adequate training of gynecologic surgeons. Payment reform is necessary to equally value women’s health procedures but also can ensure that gynecologic surgeons have the funds needed to train a competent next generation of ObGyn physicians. ●

Although rare in the United States and more common in low-resource countries, fistulas due to obstructed labor do occur. In developed countries, other obstetric causes for fistula are usually surgery, trauma, or infection related. An abnormal communication between organs—be it the urethra, bladder, ureter, uterus, cervix, or rectum—can develop¹ and lead to vesicovaginal fistula (VVF), urethrovaginal fistula (FIGURE 1), vesicocervical fistula, vesicouterine fistula, ureterovaginal fistula (FIGURE 2), and rectovaginal fistula (RVF). Other nonobstetric causes include gynecologic surgery, radiation, malignancy, and congenital malformations.

During labor, hypoxia, subsequent ischemia, and pressure necrosis contribute to fistula formation. Injury sustained during a cesarean delivery (CD) or cesarean hysterectomy can lead to fistula formation; at times, however, complications are unavoidable given the nature of the pathologic condition that the patient presents with.

VVF and RVF have a devastating impact on a woman’s quality of life as they lead to significant morbidity and short- and long-term psychological distress. The fistula may not be recognized at the time of injury. The presenting signs and symptoms may be intermittent and confusing. Immediate surgical intervention may not be possible due to ongoing inflammation or infection. Recovery often is prolonged. As there is significant concomitant postpartum anxiety and depression, patients with fistula often require psychosocial support and counseling. After repair, there is still a risk for recurrence and voiding dysfunction.

Fistula signs and symptoms and evaluation

In cases of VVF, patients present with continuing large or small volume urinary incontinence. Depending on the time to diagnosis, patients may have calculi formation, prolapse, scarring, external perineal dermatitis, perineal nerve injury, and even motor weakness. Cyclic hematuria may be seen in vesicouterine fistulas.²

Multiple classification systems for diagnosis and staging of VVF have been suggested.^3,4 A classification system for RVF was published by Tsang and colleagues.⁵ All these classification systems have attempted to characterize fistulas in terms of level of surgical complexity for repair, providing a guideline for preoperative assessment. These classification systems do not translate into prediction regarding outcomes.

Evaluation of pelvic fistula from the urinary tract starts with a thorough history that includes onset, duration, and description of leakage (continuous, intermittent, or positional) and whether there is concomitant stress and urge incontinence. A detailed obstetric history, including circumstances around the mode of delivery, underlying risk factors, and psychosocial history, should be obtained.

The pelvic examination with a plastic speculum and adequate lighting should assess the external perineum for dermatitis; bulbocavernosus and anal reflexes; and the vagina for length, caliber, level of scarring, and any prolapse. For VVFs, the location, size, and number of the fistula tracts can be visualized and confirmed with a retrograde fill of the bladder via a Foley catheter with saline or water mixed with methylene blue or any other blue dye (FIGURE 3). If a ureterovaginal fistula is suspected, the patient can simultaneously be given oral phenazopyridine and a tampon inserted within the vagina; the patient can then ambulate, and re-examination of the end of the tampon can reveal orange staining. The bladder meanwhile is retrograde filled with blue dye, with no blue staining of the tampon.

Continue to: Surgical repair...

Surgical repair

VVF repair. Factors that influence successful repair of VVF include the size and number of fistula, location, degree of scarring, bladder capacity, and urethral length.

Surgical technique requires wide mobilization and adequate exposure. The fistula tract can be delineated and manipulated with a pediatric Foley catheter, ureteral stent, or even a ureteral guidewire to aid in dissection (FIGURE 4). Intraoperative visualization of the ureters, including stenting, often is needed. The fistulous track is excised depending on the level of scarring. Closure of the bladder uroepithelium for the first layer is with absorbable interrupted 3-0 or 2-0 sutures in a tension-free closure. The bladder is then evaluated with a retrograde fill with saline and methylene blue to ensure a watertight closure for the first layer. If the first layer is not watertight, the second layer closure will not compensate and the fistula will persist. Particular attention is paid to the angles of the fistula at the first layer closure to prevent recurrence of the fistula at the angles. A running second layer with absorbable 2-0 suture is done. At times, a Martius flap or an omental J flap can be used to provide an additional layer for support and to increase vascularity.¹⁰ The patient is sent home with a Foley catheter for drainage for 10 to 14 days.¹¹ Antibiotics are not needed postoperatively for VVF surgery.¹²

CT cystogram or retrograde cystogram is usually done to evaluate closure of the fistula prior to removal of the Foley catheter; retrograde fill with contrast directly into the bladder with 300 mL is sufficient (FIGURE 5). Patients are advised to refrain from sexual activity for a minimum of 6 weeks, but depending on the level of complexity and scarring, this can be up to 12 weeks.

RVF repair. Prior to surgical repair of RVF, the integrity of the external anal sphincter must be determined. If it is not involved, a vertical incision is made in the posterior vaginal wall, the vaginal epithelium is separated from the vaginal muscularis, and the fistula tract is identified. After complete wide mobilization of the tissue surrounding the tract, it is excised. The rectal wall is repaired with 3-0 or 4-0 absorbable interrupted sutures; a second layer and if possible even a third layer and finally the vaginal epithelium are all closed with 2-0 absorbable interrupted sutures.

If the sphincter complex is involved, the dissection involves an inverted U incision separating the vaginal wall from the rectum. The fistula tract is excised, the rectal wall is closed, and the internal anal sphincter is identified and reapproximated with interrupted absorbable 2-0 or 0 sutures. The disrupted external sphincter is then reapproximated with 2-0 or 0 sutures, and finally the transverse perineal and bulbocavernosus muscles are brought together with Lembert 0 sutures prior to closure of the external skin. Perioperative antibiotics have been shown to improve success rates in the correction of RVF.⁵ In patients with sphincter trauma and known RVF, outcomes with a sphincteroplasty are better, compared with endorectal advancement flaps. The patient is discharged with a bowel regimen and dietary precautions that aim for daily soft bowel movements.

After surgical treatment of fistulas, patients benefit from pelvic floor physical therapy that focuses on pelvic floor strengthening. Incorporating the habit of Kegel exercises after every void, timed (scheduled) bladder voiding, and avoidance of straining with urination or defecation should be emphasized.

Continue to: CASE 1 Pregnant woman with rectal bleeding...

CASE 1 Pregnant woman with rectal bleeding

A 37-year-old woman at 36 3/7 weeks’ gestation presented with acute rectal bleeding and pain. This was found to result from a catastrophic rupture of a pelvic arteriovenous malformation that caused an 11 x 7 x 9.5 cm size inferior pelvic hematoma and a full-thickness rectal tear at the dentate line. During examination under anesthesia, the baby was delivered by a stat CD due to breech presentation and a prolonged fetal heart rate deceleration. The patient underwent embolization of the right middle rectal artery and right internal iliac artery by a radiologic intervention. Further bleeding required surgical intervention for evacuation of about 1,000 mL of hematoma, repair of the rectal tear, and laparoscopic diverting loop ileostomy. In total, the patient received 8 U of packed red blood cells, 6 U of fresh frozen plasma, 5 L of crystalloid solution, and 2 g of tranexamic acid. The patient reported increased foul-smelling vaginal discharge, bedside exam suggested possible fistulous tract, and on postoperative day 16, an exam under anesthesia by Urogynecology confirmed a rectovaginal fistula in the right mid vagina. After 2 months of observation to allow resolution of inflammation, successful excision of the fistula tract and repair of RVF using the above-mentioned technique was accomplished.

CASE 2 Patient with VVF after cesarean hysterectomy

A 40-year-old (G6P2222) patient underwent cesarean hysterectomy for placenta percreta and uterine rupture at 24 weeks’ gestation. Intraoperatively, there were right ureteral ligation and posterior bladder wall cystotomies. The right ureter was reimplanted in the right upper posterior wall and the cystostomies were closed. As the patient had continuous urinary leakage postoperatively, a CT urogram was obtained, which showed left ureteral obstruction and VVF. Urinary incontinence persisted despite bilateral robotic ureteral reimplantation with omental flap by the urology team. Percutaneous nephrostomy tubes were placed bilaterally. The patient underwent additional imaging studies, including MRI, with findings of VVF and possible ureterovaginal fistula.

On referral to Urogynecology, the patient underwent cystoscopy with antegrade pyelogram, and the bilateral ureteroneocystostomy orifices had 5 French open-ended ureteral stents placed. A 10 French pediatric Foley catheter was inserted intravaginally into the bladder through the VVF. Via the vaginal approach, cervical remnant and skin bridges overlying the VVF were excised. The scarred fistula tract was excised with a circumferential incision. Horizontal interrupted Lembert sutures with 3-0 absorbable suture were used to reapproximate the first layer, which was confirmed to be watertight on testing with retrograde fill. Second-layer closure was completed with horizontal mattress 2-0 absorbable sutures, followed by a third-layer closure done in similar fashion. Fibrin glue was then placed. The vaginal epithelium was closed with 2-0 absorbable suture. Percutaneous nephrostomy tubes were removed. Postoperatively, the patient had a CT cystogram with no leak and no incontinence, but she developed urgency, which was controlled with timed voids and oxybutynin. 

Although rare in the United States and more common in low-resource countries, fistulas due to obstructed labor do occur. In developed countries, other obstetric causes for fistula are usually surgery, trauma, or infection related. An abnormal communication between organs—be it the urethra, bladder, ureter, uterus, cervix, or rectum—can develop¹ and lead to vesicovaginal fistula (VVF), urethrovaginal fistula (FIGURE 1), vesicocervical fistula, vesicouterine fistula, ureterovaginal fistula (FIGURE 2), and rectovaginal fistula (RVF). Other nonobstetric causes include gynecologic surgery, radiation, malignancy, and congenital malformations.

During labor, hypoxia, subsequent ischemia, and pressure necrosis contribute to fistula formation. Injury sustained during a cesarean delivery (CD) or cesarean hysterectomy can lead to fistula formation; at times, however, complications are unavoidable given the nature of the pathologic condition that the patient presents with.

VVF and RVF have a devastating impact on a woman’s quality of life as they lead to significant morbidity and short- and long-term psychological distress. The fistula may not be recognized at the time of injury. The presenting signs and symptoms may be intermittent and confusing. Immediate surgical intervention may not be possible due to ongoing inflammation or infection. Recovery often is prolonged. As there is significant concomitant postpartum anxiety and depression, patients with fistula often require psychosocial support and counseling. After repair, there is still a risk for recurrence and voiding dysfunction.

Fistula signs and symptoms and evaluation

In cases of VVF, patients present with continuing large or small volume urinary incontinence. Depending on the time to diagnosis, patients may have calculi formation, prolapse, scarring, external perineal dermatitis, perineal nerve injury, and even motor weakness. Cyclic hematuria may be seen in vesicouterine fistulas.²

Multiple classification systems for diagnosis and staging of VVF have been suggested.^3,4 A classification system for RVF was published by Tsang and colleagues.⁵ All these classification systems have attempted to characterize fistulas in terms of level of surgical complexity for repair, providing a guideline for preoperative assessment. These classification systems do not translate into prediction regarding outcomes.

Evaluation of pelvic fistula from the urinary tract starts with a thorough history that includes onset, duration, and description of leakage (continuous, intermittent, or positional) and whether there is concomitant stress and urge incontinence. A detailed obstetric history, including circumstances around the mode of delivery, underlying risk factors, and psychosocial history, should be obtained.

The pelvic examination with a plastic speculum and adequate lighting should assess the external perineum for dermatitis; bulbocavernosus and anal reflexes; and the vagina for length, caliber, level of scarring, and any prolapse. For VVFs, the location, size, and number of the fistula tracts can be visualized and confirmed with a retrograde fill of the bladder via a Foley catheter with saline or water mixed with methylene blue or any other blue dye (FIGURE 3). If a ureterovaginal fistula is suspected, the patient can simultaneously be given oral phenazopyridine and a tampon inserted within the vagina; the patient can then ambulate, and re-examination of the end of the tampon can reveal orange staining. The bladder meanwhile is retrograde filled with blue dye, with no blue staining of the tampon.

Continue to: Surgical repair...

Surgical repair

VVF repair. Factors that influence successful repair of VVF include the size and number of fistula, location, degree of scarring, bladder capacity, and urethral length.

Surgical technique requires wide mobilization and adequate exposure. The fistula tract can be delineated and manipulated with a pediatric Foley catheter, ureteral stent, or even a ureteral guidewire to aid in dissection (FIGURE 4). Intraoperative visualization of the ureters, including stenting, often is needed. The fistulous track is excised depending on the level of scarring. Closure of the bladder uroepithelium for the first layer is with absorbable interrupted 3-0 or 2-0 sutures in a tension-free closure. The bladder is then evaluated with a retrograde fill with saline and methylene blue to ensure a watertight closure for the first layer. If the first layer is not watertight, the second layer closure will not compensate and the fistula will persist. Particular attention is paid to the angles of the fistula at the first layer closure to prevent recurrence of the fistula at the angles. A running second layer with absorbable 2-0 suture is done. At times, a Martius flap or an omental J flap can be used to provide an additional layer for support and to increase vascularity.¹⁰ The patient is sent home with a Foley catheter for drainage for 10 to 14 days.¹¹ Antibiotics are not needed postoperatively for VVF surgery.¹²

CT cystogram or retrograde cystogram is usually done to evaluate closure of the fistula prior to removal of the Foley catheter; retrograde fill with contrast directly into the bladder with 300 mL is sufficient (FIGURE 5). Patients are advised to refrain from sexual activity for a minimum of 6 weeks, but depending on the level of complexity and scarring, this can be up to 12 weeks.

RVF repair. Prior to surgical repair of RVF, the integrity of the external anal sphincter must be determined. If it is not involved, a vertical incision is made in the posterior vaginal wall, the vaginal epithelium is separated from the vaginal muscularis, and the fistula tract is identified. After complete wide mobilization of the tissue surrounding the tract, it is excised. The rectal wall is repaired with 3-0 or 4-0 absorbable interrupted sutures; a second layer and if possible even a third layer and finally the vaginal epithelium are all closed with 2-0 absorbable interrupted sutures.

If the sphincter complex is involved, the dissection involves an inverted U incision separating the vaginal wall from the rectum. The fistula tract is excised, the rectal wall is closed, and the internal anal sphincter is identified and reapproximated with interrupted absorbable 2-0 or 0 sutures. The disrupted external sphincter is then reapproximated with 2-0 or 0 sutures, and finally the transverse perineal and bulbocavernosus muscles are brought together with Lembert 0 sutures prior to closure of the external skin. Perioperative antibiotics have been shown to improve success rates in the correction of RVF.⁵ In patients with sphincter trauma and known RVF, outcomes with a sphincteroplasty are better, compared with endorectal advancement flaps. The patient is discharged with a bowel regimen and dietary precautions that aim for daily soft bowel movements.

After surgical treatment of fistulas, patients benefit from pelvic floor physical therapy that focuses on pelvic floor strengthening. Incorporating the habit of Kegel exercises after every void, timed (scheduled) bladder voiding, and avoidance of straining with urination or defecation should be emphasized.

Continue to: CASE 1 Pregnant woman with rectal bleeding...

CASE 1 Pregnant woman with rectal bleeding

A 37-year-old woman at 36 3/7 weeks’ gestation presented with acute rectal bleeding and pain. This was found to result from a catastrophic rupture of a pelvic arteriovenous malformation that caused an 11 x 7 x 9.5 cm size inferior pelvic hematoma and a full-thickness rectal tear at the dentate line. During examination under anesthesia, the baby was delivered by a stat CD due to breech presentation and a prolonged fetal heart rate deceleration. The patient underwent embolization of the right middle rectal artery and right internal iliac artery by a radiologic intervention. Further bleeding required surgical intervention for evacuation of about 1,000 mL of hematoma, repair of the rectal tear, and laparoscopic diverting loop ileostomy. In total, the patient received 8 U of packed red blood cells, 6 U of fresh frozen plasma, 5 L of crystalloid solution, and 2 g of tranexamic acid. The patient reported increased foul-smelling vaginal discharge, bedside exam suggested possible fistulous tract, and on postoperative day 16, an exam under anesthesia by Urogynecology confirmed a rectovaginal fistula in the right mid vagina. After 2 months of observation to allow resolution of inflammation, successful excision of the fistula tract and repair of RVF using the above-mentioned technique was accomplished.

CASE 2 Patient with VVF after cesarean hysterectomy

A 40-year-old (G6P2222) patient underwent cesarean hysterectomy for placenta percreta and uterine rupture at 24 weeks’ gestation. Intraoperatively, there were right ureteral ligation and posterior bladder wall cystotomies. The right ureter was reimplanted in the right upper posterior wall and the cystostomies were closed. As the patient had continuous urinary leakage postoperatively, a CT urogram was obtained, which showed left ureteral obstruction and VVF. Urinary incontinence persisted despite bilateral robotic ureteral reimplantation with omental flap by the urology team. Percutaneous nephrostomy tubes were placed bilaterally. The patient underwent additional imaging studies, including MRI, with findings of VVF and possible ureterovaginal fistula.

On referral to Urogynecology, the patient underwent cystoscopy with antegrade pyelogram, and the bilateral ureteroneocystostomy orifices had 5 French open-ended ureteral stents placed. A 10 French pediatric Foley catheter was inserted intravaginally into the bladder through the VVF. Via the vaginal approach, cervical remnant and skin bridges overlying the VVF were excised. The scarred fistula tract was excised with a circumferential incision. Horizontal interrupted Lembert sutures with 3-0 absorbable suture were used to reapproximate the first layer, which was confirmed to be watertight on testing with retrograde fill. Second-layer closure was completed with horizontal mattress 2-0 absorbable sutures, followed by a third-layer closure done in similar fashion. Fibrin glue was then placed. The vaginal epithelium was closed with 2-0 absorbable suture. Percutaneous nephrostomy tubes were removed. Postoperatively, the patient had a CT cystogram with no leak and no incontinence, but she developed urgency, which was controlled with timed voids and oxybutynin. 

Although rare in the United States and more common in low-resource countries, fistulas due to obstructed labor do occur. In developed countries, other obstetric causes for fistula are usually surgery, trauma, or infection related. An abnormal communication between organs—be it the urethra, bladder, ureter, uterus, cervix, or rectum—can develop¹ and lead to vesicovaginal fistula (VVF), urethrovaginal fistula (FIGURE 1), vesicocervical fistula, vesicouterine fistula, ureterovaginal fistula (FIGURE 2), and rectovaginal fistula (RVF). Other nonobstetric causes include gynecologic surgery, radiation, malignancy, and congenital malformations.

During labor, hypoxia, subsequent ischemia, and pressure necrosis contribute to fistula formation. Injury sustained during a cesarean delivery (CD) or cesarean hysterectomy can lead to fistula formation; at times, however, complications are unavoidable given the nature of the pathologic condition that the patient presents with.

VVF and RVF have a devastating impact on a woman’s quality of life as they lead to significant morbidity and short- and long-term psychological distress. The fistula may not be recognized at the time of injury. The presenting signs and symptoms may be intermittent and confusing. Immediate surgical intervention may not be possible due to ongoing inflammation or infection. Recovery often is prolonged. As there is significant concomitant postpartum anxiety and depression, patients with fistula often require psychosocial support and counseling. After repair, there is still a risk for recurrence and voiding dysfunction.

Fistula signs and symptoms and evaluation

In cases of VVF, patients present with continuing large or small volume urinary incontinence. Depending on the time to diagnosis, patients may have calculi formation, prolapse, scarring, external perineal dermatitis, perineal nerve injury, and even motor weakness. Cyclic hematuria may be seen in vesicouterine fistulas.²

Multiple classification systems for diagnosis and staging of VVF have been suggested.^3,4 A classification system for RVF was published by Tsang and colleagues.⁵ All these classification systems have attempted to characterize fistulas in terms of level of surgical complexity for repair, providing a guideline for preoperative assessment. These classification systems do not translate into prediction regarding outcomes.

Evaluation of pelvic fistula from the urinary tract starts with a thorough history that includes onset, duration, and description of leakage (continuous, intermittent, or positional) and whether there is concomitant stress and urge incontinence. A detailed obstetric history, including circumstances around the mode of delivery, underlying risk factors, and psychosocial history, should be obtained.

The pelvic examination with a plastic speculum and adequate lighting should assess the external perineum for dermatitis; bulbocavernosus and anal reflexes; and the vagina for length, caliber, level of scarring, and any prolapse. For VVFs, the location, size, and number of the fistula tracts can be visualized and confirmed with a retrograde fill of the bladder via a Foley catheter with saline or water mixed with methylene blue or any other blue dye (FIGURE 3). If a ureterovaginal fistula is suspected, the patient can simultaneously be given oral phenazopyridine and a tampon inserted within the vagina; the patient can then ambulate, and re-examination of the end of the tampon can reveal orange staining. The bladder meanwhile is retrograde filled with blue dye, with no blue staining of the tampon.

Continue to: Surgical repair...

Surgical repair

VVF repair. Factors that influence successful repair of VVF include the size and number of fistula, location, degree of scarring, bladder capacity, and urethral length.

Surgical technique requires wide mobilization and adequate exposure. The fistula tract can be delineated and manipulated with a pediatric Foley catheter, ureteral stent, or even a ureteral guidewire to aid in dissection (FIGURE 4). Intraoperative visualization of the ureters, including stenting, often is needed. The fistulous track is excised depending on the level of scarring. Closure of the bladder uroepithelium for the first layer is with absorbable interrupted 3-0 or 2-0 sutures in a tension-free closure. The bladder is then evaluated with a retrograde fill with saline and methylene blue to ensure a watertight closure for the first layer. If the first layer is not watertight, the second layer closure will not compensate and the fistula will persist. Particular attention is paid to the angles of the fistula at the first layer closure to prevent recurrence of the fistula at the angles. A running second layer with absorbable 2-0 suture is done. At times, a Martius flap or an omental J flap can be used to provide an additional layer for support and to increase vascularity.¹⁰ The patient is sent home with a Foley catheter for drainage for 10 to 14 days.¹¹ Antibiotics are not needed postoperatively for VVF surgery.¹²

CT cystogram or retrograde cystogram is usually done to evaluate closure of the fistula prior to removal of the Foley catheter; retrograde fill with contrast directly into the bladder with 300 mL is sufficient (FIGURE 5). Patients are advised to refrain from sexual activity for a minimum of 6 weeks, but depending on the level of complexity and scarring, this can be up to 12 weeks.

RVF repair. Prior to surgical repair of RVF, the integrity of the external anal sphincter must be determined. If it is not involved, a vertical incision is made in the posterior vaginal wall, the vaginal epithelium is separated from the vaginal muscularis, and the fistula tract is identified. After complete wide mobilization of the tissue surrounding the tract, it is excised. The rectal wall is repaired with 3-0 or 4-0 absorbable interrupted sutures; a second layer and if possible even a third layer and finally the vaginal epithelium are all closed with 2-0 absorbable interrupted sutures.

If the sphincter complex is involved, the dissection involves an inverted U incision separating the vaginal wall from the rectum. The fistula tract is excised, the rectal wall is closed, and the internal anal sphincter is identified and reapproximated with interrupted absorbable 2-0 or 0 sutures. The disrupted external sphincter is then reapproximated with 2-0 or 0 sutures, and finally the transverse perineal and bulbocavernosus muscles are brought together with Lembert 0 sutures prior to closure of the external skin. Perioperative antibiotics have been shown to improve success rates in the correction of RVF.⁵ In patients with sphincter trauma and known RVF, outcomes with a sphincteroplasty are better, compared with endorectal advancement flaps. The patient is discharged with a bowel regimen and dietary precautions that aim for daily soft bowel movements.

After surgical treatment of fistulas, patients benefit from pelvic floor physical therapy that focuses on pelvic floor strengthening. Incorporating the habit of Kegel exercises after every void, timed (scheduled) bladder voiding, and avoidance of straining with urination or defecation should be emphasized.

Continue to: CASE 1 Pregnant woman with rectal bleeding...

CASE 1 Pregnant woman with rectal bleeding

A 37-year-old woman at 36 3/7 weeks’ gestation presented with acute rectal bleeding and pain. This was found to result from a catastrophic rupture of a pelvic arteriovenous malformation that caused an 11 x 7 x 9.5 cm size inferior pelvic hematoma and a full-thickness rectal tear at the dentate line. During examination under anesthesia, the baby was delivered by a stat CD due to breech presentation and a prolonged fetal heart rate deceleration. The patient underwent embolization of the right middle rectal artery and right internal iliac artery by a radiologic intervention. Further bleeding required surgical intervention for evacuation of about 1,000 mL of hematoma, repair of the rectal tear, and laparoscopic diverting loop ileostomy. In total, the patient received 8 U of packed red blood cells, 6 U of fresh frozen plasma, 5 L of crystalloid solution, and 2 g of tranexamic acid. The patient reported increased foul-smelling vaginal discharge, bedside exam suggested possible fistulous tract, and on postoperative day 16, an exam under anesthesia by Urogynecology confirmed a rectovaginal fistula in the right mid vagina. After 2 months of observation to allow resolution of inflammation, successful excision of the fistula tract and repair of RVF using the above-mentioned technique was accomplished.

CASE 2 Patient with VVF after cesarean hysterectomy

A 40-year-old (G6P2222) patient underwent cesarean hysterectomy for placenta percreta and uterine rupture at 24 weeks’ gestation. Intraoperatively, there were right ureteral ligation and posterior bladder wall cystotomies. The right ureter was reimplanted in the right upper posterior wall and the cystostomies were closed. As the patient had continuous urinary leakage postoperatively, a CT urogram was obtained, which showed left ureteral obstruction and VVF. Urinary incontinence persisted despite bilateral robotic ureteral reimplantation with omental flap by the urology team. Percutaneous nephrostomy tubes were placed bilaterally. The patient underwent additional imaging studies, including MRI, with findings of VVF and possible ureterovaginal fistula.

On referral to Urogynecology, the patient underwent cystoscopy with antegrade pyelogram, and the bilateral ureteroneocystostomy orifices had 5 French open-ended ureteral stents placed. A 10 French pediatric Foley catheter was inserted intravaginally into the bladder through the VVF. Via the vaginal approach, cervical remnant and skin bridges overlying the VVF were excised. The scarred fistula tract was excised with a circumferential incision. Horizontal interrupted Lembert sutures with 3-0 absorbable suture were used to reapproximate the first layer, which was confirmed to be watertight on testing with retrograde fill. Second-layer closure was completed with horizontal mattress 2-0 absorbable sutures, followed by a third-layer closure done in similar fashion. Fibrin glue was then placed. The vaginal epithelium was closed with 2-0 absorbable suture. Percutaneous nephrostomy tubes were removed. Postoperatively, the patient had a CT cystogram with no leak and no incontinence, but she developed urgency, which was controlled with timed voids and oxybutynin. 

The operating room (OR) is a key contributor to a hospital’s profitability. It is a complex environment with ever-advancing technology. A successful surgery completed without complications within an optimal time depends not only on the surgeon’s experience, skills, and knowledge but also on numerous other structural, human, and nontechnical factors over which the surgeon has limited control.

As in any setting that deals with human life, in the OR, team dynamics, communication, and environment play a major role. Research has indicated the benefits of dedicated teams, reduced handoffs, and innovative modalities that continuously and systematically monitor potential breakdowns and propose solutions for the detected problems.

Finally, who should perform your loved one’s hysterectomy? This article also attempts to address the impact of surgeons’ and hospitals’ volume on operative outcomes with a diminishing number of hysterectomies but an increasing number of approaches.

Human factors in the OR

Human factors research was born as a product of the industrial revolution and mass production. It aims to optimize human experience and improve system performance by studying how humans interact with system. The aviation industry, for example, minimized errors significantly by using methods developed by human factors scientists. As another industry with no tolerance for mistakes, the health care sector followed suit. Ultimately, the goal of human factors research in health care is to improve patient safety, optimize work and environment, reduce costs, and enhance employees’ physical and mental health, engagement, comfort, and quality of life (FIGURE 1).¹