OBG Management

How do you feel about expectantly managing a well-dated pregnancy past 41 weeks’ gestation?

ROBERT L. BARBIERI, MD

(EDITORIAL; FEBRUARY 2019) 

Is it reasonable to choose the age of 40 for proposing an anticipation of labor induction?

In physiologic ongoing pregnancies (whether they are spontaneous or autologous in vitro fertilization [IVF] or heterologous IVF), the evidence for anticipating labor induction based upon the only factor of age (after 40 years) is missing. Nonetheless, the number of women becoming pregnant at an older age is expected to increase, and from my perspective, to induce all physiologic pregnancies at term by 41 weeks and 5 days’ gestation does not appear to be best practice. I favor the idea of all women aged 40 and older to start labor induction earlier (for instance, to offer labor induction, with proper informed consent, by 41+ 0 and not 41+ 5 through 42+ 0 weeks of pregnancy).

Luca Bernardini, MD

La Spezia, Italy 

Dr. Barbieri responds

At Brigham and Women’s Hospital in Boston, Massachusetts, our approach is to offer women ≥40 years of age induction of labor (IOL) at 39 weeks’ gestation, unless there is an obstetric contraindication to IOL. We believe that IOL at 39 weeks’ gestation is associated with a reduced risk of both cesarean delivery and a new diagnosis of hypertension.¹

Reference

1. Grobman WA, Rice MM, Reddy, UM, et al. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

What is the optimal hormonal treatment for women with polycystic ovary syndrome?

ROBERT L. BARBIERI, MD

(EDITORIAL; JANUARY 2020)

OCs and spironolactone study

I often recommend oral contraceptives (OCs) containing drospirenone for patients with polycyctic ovary syndrome (PCOS)-associated mild acne and hirsutism—since OCs are already approved by the US Food and Drug Administration for acne, with similar effects as spironolactone. My patients seem to do well on an OC, and require only one medication. Of course, I would add spironolactone to the treatment regimen and switch OCs if she was not responding well.

Michael T. Cane, MD

Arlington, Texas

Dr. Barbieri responds

The Endocrine Society agrees with Dr. Cane’s approach, recommending the initiation of monotherapy with an estrogen-progestin followed by the addition of spironolactone if 6 months of monotherapy produces insufficient improvement in dermatologic symptoms of PCOS, including hirsutism and acne. Most contraceptives contain 3 mg or 4 mg of drospirenone, which is thought to have antiandrogenic effects similar to spironolactone 25 mg. I believe that spironolactone 100 mg provides more complete and rapid resolution of the dermatologic symptoms caused by PCOS. Hence, I initiate both an estrogen-progestin contraceptive with spironolactone.

How do you feel about expectantly managing a well-dated pregnancy past 41 weeks’ gestation?

ROBERT L. BARBIERI, MD

(EDITORIAL; FEBRUARY 2019) 

Is it reasonable to choose the age of 40 for proposing an anticipation of labor induction?

In physiologic ongoing pregnancies (whether they are spontaneous or autologous in vitro fertilization [IVF] or heterologous IVF), the evidence for anticipating labor induction based upon the only factor of age (after 40 years) is missing. Nonetheless, the number of women becoming pregnant at an older age is expected to increase, and from my perspective, to induce all physiologic pregnancies at term by 41 weeks and 5 days’ gestation does not appear to be best practice. I favor the idea of all women aged 40 and older to start labor induction earlier (for instance, to offer labor induction, with proper informed consent, by 41+ 0 and not 41+ 5 through 42+ 0 weeks of pregnancy).

Luca Bernardini, MD

La Spezia, Italy 

Dr. Barbieri responds

At Brigham and Women’s Hospital in Boston, Massachusetts, our approach is to offer women ≥40 years of age induction of labor (IOL) at 39 weeks’ gestation, unless there is an obstetric contraindication to IOL. We believe that IOL at 39 weeks’ gestation is associated with a reduced risk of both cesarean delivery and a new diagnosis of hypertension.¹

Reference

1. Grobman WA, Rice MM, Reddy, UM, et al. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

What is the optimal hormonal treatment for women with polycystic ovary syndrome?

ROBERT L. BARBIERI, MD

(EDITORIAL; JANUARY 2020)

OCs and spironolactone study

I often recommend oral contraceptives (OCs) containing drospirenone for patients with polycyctic ovary syndrome (PCOS)-associated mild acne and hirsutism—since OCs are already approved by the US Food and Drug Administration for acne, with similar effects as spironolactone. My patients seem to do well on an OC, and require only one medication. Of course, I would add spironolactone to the treatment regimen and switch OCs if she was not responding well.

Michael T. Cane, MD

Arlington, Texas

Dr. Barbieri responds

The Endocrine Society agrees with Dr. Cane’s approach, recommending the initiation of monotherapy with an estrogen-progestin followed by the addition of spironolactone if 6 months of monotherapy produces insufficient improvement in dermatologic symptoms of PCOS, including hirsutism and acne. Most contraceptives contain 3 mg or 4 mg of drospirenone, which is thought to have antiandrogenic effects similar to spironolactone 25 mg. I believe that spironolactone 100 mg provides more complete and rapid resolution of the dermatologic symptoms caused by PCOS. Hence, I initiate both an estrogen-progestin contraceptive with spironolactone.

How do you feel about expectantly managing a well-dated pregnancy past 41 weeks’ gestation?

ROBERT L. BARBIERI, MD

(EDITORIAL; FEBRUARY 2019) 

Is it reasonable to choose the age of 40 for proposing an anticipation of labor induction?

In physiologic ongoing pregnancies (whether they are spontaneous or autologous in vitro fertilization [IVF] or heterologous IVF), the evidence for anticipating labor induction based upon the only factor of age (after 40 years) is missing. Nonetheless, the number of women becoming pregnant at an older age is expected to increase, and from my perspective, to induce all physiologic pregnancies at term by 41 weeks and 5 days’ gestation does not appear to be best practice. I favor the idea of all women aged 40 and older to start labor induction earlier (for instance, to offer labor induction, with proper informed consent, by 41+ 0 and not 41+ 5 through 42+ 0 weeks of pregnancy).

Luca Bernardini, MD

La Spezia, Italy 

Dr. Barbieri responds

At Brigham and Women’s Hospital in Boston, Massachusetts, our approach is to offer women ≥40 years of age induction of labor (IOL) at 39 weeks’ gestation, unless there is an obstetric contraindication to IOL. We believe that IOL at 39 weeks’ gestation is associated with a reduced risk of both cesarean delivery and a new diagnosis of hypertension.¹

Reference

1. Grobman WA, Rice MM, Reddy, UM, et al. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379:513-523.

What is the optimal hormonal treatment for women with polycystic ovary syndrome?

ROBERT L. BARBIERI, MD

(EDITORIAL; JANUARY 2020)

OCs and spironolactone study

I often recommend oral contraceptives (OCs) containing drospirenone for patients with polycyctic ovary syndrome (PCOS)-associated mild acne and hirsutism—since OCs are already approved by the US Food and Drug Administration for acne, with similar effects as spironolactone. My patients seem to do well on an OC, and require only one medication. Of course, I would add spironolactone to the treatment regimen and switch OCs if she was not responding well.

Michael T. Cane, MD

Arlington, Texas

Dr. Barbieri responds

The Endocrine Society agrees with Dr. Cane’s approach, recommending the initiation of monotherapy with an estrogen-progestin followed by the addition of spironolactone if 6 months of monotherapy produces insufficient improvement in dermatologic symptoms of PCOS, including hirsutism and acne. Most contraceptives contain 3 mg or 4 mg of drospirenone, which is thought to have antiandrogenic effects similar to spironolactone 25 mg. I believe that spironolactone 100 mg provides more complete and rapid resolution of the dermatologic symptoms caused by PCOS. Hence, I initiate both an estrogen-progestin contraceptive with spironolactone.

CASE Woman with bleeding in early pregnancy

A 31-year-old woman (G1P0) presents to the local emergency department (ED) due to bleeding in pregnancy. She reports a prior open appendectomy for ruptured appendix; she denies a history of sexually transmitted infections, smoking, and contraception use. She reports having regular menstrual cycles and trying to conceive with her husband for 18 months without success until now.

The patient reports that the previous week she took a home pregnancy test that was positive; she endorses having dark brown spotting for the past 2 days but denies pain. Based on the date of her last menstrual period, gestational age is estimated to be 5 weeks and 1 day. Her human chorionic gonadotropin (hCG) level is 1,670 mIU/mL. Transvaginal ultrasonography demonstrates a normal uterus with an endometrial thickness of 10 mm, no evidence of an intrauterine pregnancy (IUP), normal adnexa bilaterally, and scant free fluid in the pelvis.

Identifying and evaluating pregnancy of unknown location

A pregnancy of unknown location (PUL) is defined by a positive serum hCG level in the absence of a visualized IUP or ectopic pregnancy (EP) by pelvic ultrasonography.

Because of variations in screening tools and clinical practices between institutions and care settings (for example, EDs versus specialized outpatient offices), the incidence of PUL is difficult to capture. In specialized early pregnancy clinics, the rate is 8% to 10%, whereas in the ED setting, the PUL rate has been reported to be as high as 42%.^1-6 While approximately 98% to 99% of all pregnancies are intrauterine, only 30% of PULs will continue to develop as viable ongoing intrauterine gestations.^7-9 The remainder are revealed as failing IUPs or EPs. To counsel patients, set expectations, and triage to appropriate management, it is critical to diagnose pregnancy location as efficiently as possible.

Ectopic pregnancy

Ectopic pregnancies represent only 1% to 2% of conceptions (both spontaneous and through assisted reproduction) and occur most commonly in the fallopian tube, although EPs also can implant in the cornua of the uterus, the cervix, cesarean scar, and more rarely on the ovary or abdominal viscera.^10,11 Least common, heterotopic pregnancies—in which an IUP coexists with an EP—occur in 1 in 4,000 to 30,000 pregnancies, more commonly in women who used assisted reproduction.¹¹

Major risk factors for EP include a history of tubal surgery, sexually transmitted infections (particularly Chlamydia trachomatis), pelvic inflammatory disease, conception with an intrauterine device in situ, and a history of prior EP or tubal surgery, particularly prior tubal ligation; minor risk factors include a history of infertility (excluding known tubal factor infertility) or smoking (in a dose-dependent manner).^11,12 The concern for an EP is heightened in patients with these risk factors.

Because of the possibility of rupture and life-threatening hemorrhage, EP carries a risk of significant morbidity and mortality.¹³ Ruptured EPs account for approximately 2.7% of all maternal deaths each year.¹⁴ When diagnosed sufficiently early in a stable patient, most EPs can be managed medically with methotrexate, a folic acid antagonist.¹⁵ Ectopic pregnancies also may be managed surgically, and emergency surgery is indicated in women with evidence of EP rupture and intraperitoneal bleeding.

Continue to: Intrauterine pregnancy...

Intrauterine pregnancy

While excluding EP is critical, it is equally important to diagnose an IUP as expeditiously as possible to avoid inadvertent, destructive intervention. Diagnosis and management of a PUL can involve endometrial aspiration, which would interrupt an IUP and should be avoided until the possibility of a viable IUP has been eliminated in desired pregnancies. The inadvertent administration of methotrexate, a known teratogen, to a patient with an undiagnosed viable IUP can result in miscarriage, elective termination, or a live-born infant with significant malformations, all of which expose the administering physician to malpractice litigation.^16,17

In desired pregnancies, it is essential to differentiate between a viable IUP, a nonviable IUP, and an EP to guide appropriate management and ensure patient safety, whereas exclusion of EP is the priority in undesired pregnancies.

Tools for diagnosing pregnancy location

For diagnosing pregnancy location, serial hCG measurement, transvaginal pelvic ultrasonography, and outpatient endometrial aspiration are all relevant clinical tools. Pregnancy location can be diagnosed with either direct visualization of an IUP or EP by ultrasonography or with confirmed pathology (chorionic villi or trophoblast cells) from endometrial aspiration (FIGURE). A decline in hCG to an undetectable level following endometrial aspiration also is considered sufficient to diagnose a failed IUP, even in the absence of a confirmatory ultrasonography.

Trending hCG values

In stable patients with PUL, serum hCG levels are commonly measured at 2-day intervals, ideally for a minimum of 3 values. Conventional wisdom dictates that in viable IUPs, the hCG level should roughly double every 2 days. However, more recent data suggest that the threshold for minimum expected hCG rise for an ongoing IUP should be far lower when the pregnancy is desired.¹⁸ A less conservative cutoff can be considered when a pregnancy is not desired.

In a multisite cohort study of 1,005 women with PUL, a minimum hCG rise of 35% in 2 days captured the majority of IUPs, with a negative predictive value of 97.2% for IUP.¹⁹ Of note, although the cutoff of 35% was selected to reduce the risk of misdiagnosing an IUP as an EP, 7.7% of IUPs (and 16.8% of EPs) were still misclassified, showing that hCG trends must be interpreted in the context of other clinical data, including ultrasonography findings and patient symptoms and history.

A follow-up study demonstrated that hCG rises are lower (but still within this normal range) when the initial hCG value is higher, particularly greater than 3,000 mIU/mL.²⁰

Studies show that the rate of spontaneous hCG decline in failing IUPs ranges from 12% to 47% in 2 days, falling more rapidly from higher starting hCG values.^19,21 In a retrospective review of 443 women with spontaneously resolving PUL (presumed to be failing IUPs), the minimum 2-day decline in hCG was 35%.²² Any spontaneous hCG decline less than 35% in 2 days in a PUL should raise physician concern for EP.

Conversely, EPs do not demonstrate predictable hCG trends and can mimic the hCG trends of viable or failing IUPs. Although typically half of EPs present with an increasing hCG value and half present with a decreasing hCG value, the majority (71%) demonstrate a slower rate of change than either a viable IUP or a miscarriage.¹¹ This slower change (plateau) should heighten the clinician’s suspicion for an EP.

Continue to: Progesterone levels...

Progesterone levels

A progesterone level often is used to attempt to determine pregnancy viability in women who are not receiving progesterone supplementation, although it ultimately has limited utility. While far less sensitive than an hCG value trend, a serum progesterone level of less than 5 to 10 ng/mL is a rough marker of nonviable pregnancy.²³

In a large meta-analysis of women with pain and bleeding, 96.8% of pregnancies with a single progesterone level of less than 10 ng/mL were nonviable.²³ When an inconclusive ultrasonography was documented in addition to symptoms of pain and bleeding, 99.2% of pregnancies with a progesterone level of less than 3.2 to 6 ng/mL were nonviable.

Progesterone’s usefulness in assessing for a PUL is limited: While progesterone levels may indicate nonviability, they provide no indication of pregnancy location (intrauterine or ectopic).

Alternative serologic markers

Various other reproductive and pregnancy-related hormones have been investigated for use in the diagnosis of pregnancy location in PULs, including activin A, inhibin A, pregnancy-associated plasma protein A (PAPP-A), placental-like growth factor, vascular endothelial growth factor, follistatin, and various microRNAs.^24,25 While research into these biomarkers is ongoing, none have been studied in prospective trials, and they are not for use in current clinical care.

Pelvic ultrasonography

Pelvic ultrasonography is a crucial part of PUL assessment. Transvaginal ultrasonography should be interpreted in the context of the estimated gestational age of the pregnancy and serial hCG values, if available; the patient’s symptoms; and the sensitivity of the ultrasonography equipment, which also may be affected by variables that can reduce visualization, such as uterine fibroids and obesity.

The “discriminatory zone” refers to the hCG value above which an IUP should be visualized by ultrasonography. Generally, with an hCG value of 1,500 to 2,000 mIU/mL or greater, an IUP is expected to be seen with transvaginal sonography.^3,26 Many exceptions to the discriminatory zone have been reported, however, including multiple pregnancies, which will have a higher hCG value at an earlier gestational age. Even in singleton pregnancies, viable IUPs have been documented as developing from PULs with an elevated initial hCG value as high as 4,300 mIU/mL.²⁷ The discriminatory zone may vary among clinical hCG assays, and it also is affected by the quality and modernity of the ultrasonography equipment as well as by the ultrasonography operator’s experience and skill.^28,29

The estimated gestational age, based on either the last menstrual period or assisted reproduction procedure, provides a helpful data point to guide expectations for ultrasonography findings.³⁰ Using transvaginal ultrasonography in a normally progressing IUP, a gestational sac—typically measuring 2 to 3 mm—should be visualized at 5 weeks.^15,30 At approximately 5.5 weeks, a yolk sac measuring 3 to 5 mm should appear. At 6 weeks, an embryo with cardiac activity should be visualized.

In a pregnancy reliably dated beyond 5 weeks, the lack of an intrauterine gestational sac is suspicious for, but not diagnostic of, an EP. Conversely, the visualization of a gestational sac alone (without a yolk sac) is insufficient to definitively exclude an EP, since a small fluid collection in the endometrium (a “pseudosac”) can convincingly mimic the appearance of a gestational sac, and a follow-up ultrasonography should be performed in such cases.

Among patients without ultrasonographic evidence of an IUP, endometrial thickness has been posited as a way to differentiate between IUP and EP.^31,32 Evidence suggests that an endometrial stripe of at least 8 to 10 mm may be somewhat predictive of an IUP, while endometrial thickness below 8 mm is more concerning for EP. This clinical variable, however, has been shown repeatedly to lack sufficient sensitivity and specificity for IUP and should be considered only within the entire clinical context.

Continue to: Endometrial aspiration...

Endometrial aspiration

A persistently abnormal hCG trend and an ultrasonography without evidence of an IUP—particularly with an hCG value above the discriminatory zone and/or with reliable pregnancy dating beyond 5 to 6 weeks—is highly concerning for either a failing IUP or an EP. Once a viable desired IUP is excluded beyond reasonable doubt through these measures, endometrial aspiration to determine pregnancy location is a reasonable next step in PUL management.

Endometrial aspiration can identify a failing IUP by detection of trophoblasts or chorionic villi on pathology and/or by a decline of at least 15% in hCG, measured on the day of endometrial aspiration and again the following day. Endometrial aspiration is effective even in clinical care settings that do not have rapid pathologic analysis available, as hCG measurement before and within 24 hours after the procedure still can be performed.

Vacuum aspiration (electric or manual) in an operating room or office setting is an effective tool for diagnosing pregnancy location.^33,34 The use of an endometrial Pipelle for endometrial sampling (typically used for an office endometrial biopsy to diagnose hyperplasia or malignancy) is insufficient for determining pregnancy location.³⁵ For all patients managed with this protocol, the hCG value ideally should be followed until it is undetectable, regardless of whether an EP or failing IUP was diagnosed. In rare cases, an EP may be diagnosed by a late plateau in hCG values, following an initial decline consistent with a failing IUP.

Utility for diagnosis. Retrospective studies in patients with PUL following in vitro fertilization have established the utility of outpatient endometrial aspiration with a Karman cannula, followed by a repeat hCG measurement on the day after the procedure.^34,36 These data demonstrate that between 42% and 69% of women were ultimately diagnosed with a failed IUP following endometrial aspiration, thereby sparing them unnecessary exposure to methotrexate.

A decline in hCG levels of at least 15% within 24 hours after the procedure indicates that a failed IUP is the most likely diagnosis and further intervention is not indicated (although falling hCG values should be monitored for confirmation); confirmatory pathology with chorionic villi or trophoblasts was present in less than half of these women and is not necessary to diagnose a failed IUP.³⁶ Women diagnosed with a failed IUP after endometrial aspiration also benefitted from a shorter time to resolution of the nonviable pregnancy by approximately 2 weeks.³⁶

Despite the efficacy of endometrial aspiration for the diagnosis of pregnancy location, recent data show that physicians have highly variable approaches to PUL with an hCG plateaued above the discriminatory zone: One-third would first perform endometrial aspiration, while one-third would give methotrexate without further diagnostics.³⁷ Academic physicians were 4 times more likely to recommend endometrial aspiration.³⁷

Presumed EP. Following endometrial aspiration, if pathology does not confirm an intrauterine gestation and the hCG fails to decline by at least 15%, the diagnosis of a presumed EP is made.

For stable patients with neither evidence of intra-abdominal bleeding nor contraindications to methotrexate (such as blood dyscrasias, hepatic or renal insufficiency, active pulmonary or peptic ulcer disease, breastfeeding, or a known intolerance to the medication), methotrexate is recommended for medical management.²⁶ Following screening blood work that includes a complete blood count and liver function and renal function tests, the typical methotrexate dose is 50 mg/m² of body surface area. The single-dose regimen entails checking hCG on the day of methotrexate administration and again on days 4 and 7 thereafter. A minimum decline in hCG of 15% between days 4 and 7 indicates successful treatment; if the hCG decline is below 15%, the patient should receive an additional dose of methotrexate.

There are several published alternative regimens for methotrexate administration, including 2-dose and multidose regimens; the 2-dose protocol (2 doses within 7 days) may be more effective in women with higher hCG (> 3,000 mIU/mL) or known adnexal mass.^26,38

Continue to: Contraindications to methotrexate...

Contraindications to methotrexate. In addition to strict medical contraindications to methotrexate, relative contraindications that indicate a higher risk of methotrexate failure include the presence of fetal cardiac activity, EP mass greater than 4 cm, and serum hCG above 5,000 mIU/mL.²⁶ Because of the potential risk of tubal rupture during medical management, relative contraindications also include patient inability to follow up as an outpatient and patient refusal of blood transfusion.²⁶ Patients with contraindications to methotrexate, hemodynamic instability, ultrasonographic or clinical evidence of EP rupture, or those electing for surgical management may be managed with laparoscopy.¹¹ Discussion of surgical management of EP is beyond the scope of this article.

Follow the hCG level. In patients with a failing IUP or an EP treated with methotrexate or salpingostomy, the hCG level should always be followed until it is negative, usually by weekly measurements once the diagnosis is made. In some cases, the hCG level may plateau after an initial decline, alerting the clinician to failed treatment for a known EP or the need for recategorization of a failed IUP as an EP.

CASE Concluded

The patient’s second and third hCG measurements at 2-day intervals were 1,903 mIU/mL (14% rise) and 2,264 mIU/mL (16% rise). At that point, a repeat transvaginal ultrasonography showed no IUP, adnexal mass, or free fluid. The patient was counseled for outpatient endometrial aspiration, which was performed using manual vacuum aspiration. The serum hCG level on the morning of the procedure was 2,420 mIU/mL. On postprocedure day 1, the serum hCG level fell to 1,615 mIU/mL, a 33% decline. The patient was counseled that this decline in hCG indicated a failing IUP. The final pathologic analysis was returned 3 days later, showing no evidence of trophoblasts and chorionic villi. Regardless, the diagnosis of failing IUP remained given the rapid hCG decline; the tissue from the disrupted failing IUP was likely very scant or simply not drawn into the cannula. Serum hCG levels repeated at weekly intervals revealed ongoing decline, and after 4 weeks, the serum hCG was negative.

In summary

For women diagnosed with PUL, the primary goal is to distinguish an IUP from an EP to reduce the risk of EP rupture through expeditious diagnosis and treatment. In women for whom the pregnancy is desired, distinguishing a viable IUP from a nonviable IUP or an EP is the more specific goal to avoid intervention on a viable IUP (with methotrexate or endometrial aspiration). In women with abnormal hCG trends and indeterminate ultrasonography results (particularly with a serum hCG above the discriminatory zone), outpatient endometrial aspiration is a highly effective way to determine pregnancy location, which dictates further treatment. ●

CASE Woman with bleeding in early pregnancy

A 31-year-old woman (G1P0) presents to the local emergency department (ED) due to bleeding in pregnancy. She reports a prior open appendectomy for ruptured appendix; she denies a history of sexually transmitted infections, smoking, and contraception use. She reports having regular menstrual cycles and trying to conceive with her husband for 18 months without success until now.

The patient reports that the previous week she took a home pregnancy test that was positive; she endorses having dark brown spotting for the past 2 days but denies pain. Based on the date of her last menstrual period, gestational age is estimated to be 5 weeks and 1 day. Her human chorionic gonadotropin (hCG) level is 1,670 mIU/mL. Transvaginal ultrasonography demonstrates a normal uterus with an endometrial thickness of 10 mm, no evidence of an intrauterine pregnancy (IUP), normal adnexa bilaterally, and scant free fluid in the pelvis.

Identifying and evaluating pregnancy of unknown location

A pregnancy of unknown location (PUL) is defined by a positive serum hCG level in the absence of a visualized IUP or ectopic pregnancy (EP) by pelvic ultrasonography.

Because of variations in screening tools and clinical practices between institutions and care settings (for example, EDs versus specialized outpatient offices), the incidence of PUL is difficult to capture. In specialized early pregnancy clinics, the rate is 8% to 10%, whereas in the ED setting, the PUL rate has been reported to be as high as 42%.^1-6 While approximately 98% to 99% of all pregnancies are intrauterine, only 30% of PULs will continue to develop as viable ongoing intrauterine gestations.^7-9 The remainder are revealed as failing IUPs or EPs. To counsel patients, set expectations, and triage to appropriate management, it is critical to diagnose pregnancy location as efficiently as possible.

Ectopic pregnancy

Ectopic pregnancies represent only 1% to 2% of conceptions (both spontaneous and through assisted reproduction) and occur most commonly in the fallopian tube, although EPs also can implant in the cornua of the uterus, the cervix, cesarean scar, and more rarely on the ovary or abdominal viscera.^10,11 Least common, heterotopic pregnancies—in which an IUP coexists with an EP—occur in 1 in 4,000 to 30,000 pregnancies, more commonly in women who used assisted reproduction.¹¹

Major risk factors for EP include a history of tubal surgery, sexually transmitted infections (particularly Chlamydia trachomatis), pelvic inflammatory disease, conception with an intrauterine device in situ, and a history of prior EP or tubal surgery, particularly prior tubal ligation; minor risk factors include a history of infertility (excluding known tubal factor infertility) or smoking (in a dose-dependent manner).^11,12 The concern for an EP is heightened in patients with these risk factors.

Because of the possibility of rupture and life-threatening hemorrhage, EP carries a risk of significant morbidity and mortality.¹³ Ruptured EPs account for approximately 2.7% of all maternal deaths each year.¹⁴ When diagnosed sufficiently early in a stable patient, most EPs can be managed medically with methotrexate, a folic acid antagonist.¹⁵ Ectopic pregnancies also may be managed surgically, and emergency surgery is indicated in women with evidence of EP rupture and intraperitoneal bleeding.

Continue to: Intrauterine pregnancy...

Intrauterine pregnancy

While excluding EP is critical, it is equally important to diagnose an IUP as expeditiously as possible to avoid inadvertent, destructive intervention. Diagnosis and management of a PUL can involve endometrial aspiration, which would interrupt an IUP and should be avoided until the possibility of a viable IUP has been eliminated in desired pregnancies. The inadvertent administration of methotrexate, a known teratogen, to a patient with an undiagnosed viable IUP can result in miscarriage, elective termination, or a live-born infant with significant malformations, all of which expose the administering physician to malpractice litigation.^16,17

In desired pregnancies, it is essential to differentiate between a viable IUP, a nonviable IUP, and an EP to guide appropriate management and ensure patient safety, whereas exclusion of EP is the priority in undesired pregnancies.

Tools for diagnosing pregnancy location

For diagnosing pregnancy location, serial hCG measurement, transvaginal pelvic ultrasonography, and outpatient endometrial aspiration are all relevant clinical tools. Pregnancy location can be diagnosed with either direct visualization of an IUP or EP by ultrasonography or with confirmed pathology (chorionic villi or trophoblast cells) from endometrial aspiration (FIGURE). A decline in hCG to an undetectable level following endometrial aspiration also is considered sufficient to diagnose a failed IUP, even in the absence of a confirmatory ultrasonography.

Trending hCG values

In stable patients with PUL, serum hCG levels are commonly measured at 2-day intervals, ideally for a minimum of 3 values. Conventional wisdom dictates that in viable IUPs, the hCG level should roughly double every 2 days. However, more recent data suggest that the threshold for minimum expected hCG rise for an ongoing IUP should be far lower when the pregnancy is desired.¹⁸ A less conservative cutoff can be considered when a pregnancy is not desired.

In a multisite cohort study of 1,005 women with PUL, a minimum hCG rise of 35% in 2 days captured the majority of IUPs, with a negative predictive value of 97.2% for IUP.¹⁹ Of note, although the cutoff of 35% was selected to reduce the risk of misdiagnosing an IUP as an EP, 7.7% of IUPs (and 16.8% of EPs) were still misclassified, showing that hCG trends must be interpreted in the context of other clinical data, including ultrasonography findings and patient symptoms and history.

A follow-up study demonstrated that hCG rises are lower (but still within this normal range) when the initial hCG value is higher, particularly greater than 3,000 mIU/mL.²⁰

Studies show that the rate of spontaneous hCG decline in failing IUPs ranges from 12% to 47% in 2 days, falling more rapidly from higher starting hCG values.^19,21 In a retrospective review of 443 women with spontaneously resolving PUL (presumed to be failing IUPs), the minimum 2-day decline in hCG was 35%.²² Any spontaneous hCG decline less than 35% in 2 days in a PUL should raise physician concern for EP.

Conversely, EPs do not demonstrate predictable hCG trends and can mimic the hCG trends of viable or failing IUPs. Although typically half of EPs present with an increasing hCG value and half present with a decreasing hCG value, the majority (71%) demonstrate a slower rate of change than either a viable IUP or a miscarriage.¹¹ This slower change (plateau) should heighten the clinician’s suspicion for an EP.

Continue to: Progesterone levels...

Progesterone levels

A progesterone level often is used to attempt to determine pregnancy viability in women who are not receiving progesterone supplementation, although it ultimately has limited utility. While far less sensitive than an hCG value trend, a serum progesterone level of less than 5 to 10 ng/mL is a rough marker of nonviable pregnancy.²³

In a large meta-analysis of women with pain and bleeding, 96.8% of pregnancies with a single progesterone level of less than 10 ng/mL were nonviable.²³ When an inconclusive ultrasonography was documented in addition to symptoms of pain and bleeding, 99.2% of pregnancies with a progesterone level of less than 3.2 to 6 ng/mL were nonviable.

Progesterone’s usefulness in assessing for a PUL is limited: While progesterone levels may indicate nonviability, they provide no indication of pregnancy location (intrauterine or ectopic).

Alternative serologic markers

Various other reproductive and pregnancy-related hormones have been investigated for use in the diagnosis of pregnancy location in PULs, including activin A, inhibin A, pregnancy-associated plasma protein A (PAPP-A), placental-like growth factor, vascular endothelial growth factor, follistatin, and various microRNAs.^24,25 While research into these biomarkers is ongoing, none have been studied in prospective trials, and they are not for use in current clinical care.

Pelvic ultrasonography

Pelvic ultrasonography is a crucial part of PUL assessment. Transvaginal ultrasonography should be interpreted in the context of the estimated gestational age of the pregnancy and serial hCG values, if available; the patient’s symptoms; and the sensitivity of the ultrasonography equipment, which also may be affected by variables that can reduce visualization, such as uterine fibroids and obesity.

The “discriminatory zone” refers to the hCG value above which an IUP should be visualized by ultrasonography. Generally, with an hCG value of 1,500 to 2,000 mIU/mL or greater, an IUP is expected to be seen with transvaginal sonography.^3,26 Many exceptions to the discriminatory zone have been reported, however, including multiple pregnancies, which will have a higher hCG value at an earlier gestational age. Even in singleton pregnancies, viable IUPs have been documented as developing from PULs with an elevated initial hCG value as high as 4,300 mIU/mL.²⁷ The discriminatory zone may vary among clinical hCG assays, and it also is affected by the quality and modernity of the ultrasonography equipment as well as by the ultrasonography operator’s experience and skill.^28,29

The estimated gestational age, based on either the last menstrual period or assisted reproduction procedure, provides a helpful data point to guide expectations for ultrasonography findings.³⁰ Using transvaginal ultrasonography in a normally progressing IUP, a gestational sac—typically measuring 2 to 3 mm—should be visualized at 5 weeks.^15,30 At approximately 5.5 weeks, a yolk sac measuring 3 to 5 mm should appear. At 6 weeks, an embryo with cardiac activity should be visualized.

In a pregnancy reliably dated beyond 5 weeks, the lack of an intrauterine gestational sac is suspicious for, but not diagnostic of, an EP. Conversely, the visualization of a gestational sac alone (without a yolk sac) is insufficient to definitively exclude an EP, since a small fluid collection in the endometrium (a “pseudosac”) can convincingly mimic the appearance of a gestational sac, and a follow-up ultrasonography should be performed in such cases.

Among patients without ultrasonographic evidence of an IUP, endometrial thickness has been posited as a way to differentiate between IUP and EP.^31,32 Evidence suggests that an endometrial stripe of at least 8 to 10 mm may be somewhat predictive of an IUP, while endometrial thickness below 8 mm is more concerning for EP. This clinical variable, however, has been shown repeatedly to lack sufficient sensitivity and specificity for IUP and should be considered only within the entire clinical context.

Continue to: Endometrial aspiration...

Endometrial aspiration

A persistently abnormal hCG trend and an ultrasonography without evidence of an IUP—particularly with an hCG value above the discriminatory zone and/or with reliable pregnancy dating beyond 5 to 6 weeks—is highly concerning for either a failing IUP or an EP. Once a viable desired IUP is excluded beyond reasonable doubt through these measures, endometrial aspiration to determine pregnancy location is a reasonable next step in PUL management.

Endometrial aspiration can identify a failing IUP by detection of trophoblasts or chorionic villi on pathology and/or by a decline of at least 15% in hCG, measured on the day of endometrial aspiration and again the following day. Endometrial aspiration is effective even in clinical care settings that do not have rapid pathologic analysis available, as hCG measurement before and within 24 hours after the procedure still can be performed.

Vacuum aspiration (electric or manual) in an operating room or office setting is an effective tool for diagnosing pregnancy location.^33,34 The use of an endometrial Pipelle for endometrial sampling (typically used for an office endometrial biopsy to diagnose hyperplasia or malignancy) is insufficient for determining pregnancy location.³⁵ For all patients managed with this protocol, the hCG value ideally should be followed until it is undetectable, regardless of whether an EP or failing IUP was diagnosed. In rare cases, an EP may be diagnosed by a late plateau in hCG values, following an initial decline consistent with a failing IUP.

Utility for diagnosis. Retrospective studies in patients with PUL following in vitro fertilization have established the utility of outpatient endometrial aspiration with a Karman cannula, followed by a repeat hCG measurement on the day after the procedure.^34,36 These data demonstrate that between 42% and 69% of women were ultimately diagnosed with a failed IUP following endometrial aspiration, thereby sparing them unnecessary exposure to methotrexate.

A decline in hCG levels of at least 15% within 24 hours after the procedure indicates that a failed IUP is the most likely diagnosis and further intervention is not indicated (although falling hCG values should be monitored for confirmation); confirmatory pathology with chorionic villi or trophoblasts was present in less than half of these women and is not necessary to diagnose a failed IUP.³⁶ Women diagnosed with a failed IUP after endometrial aspiration also benefitted from a shorter time to resolution of the nonviable pregnancy by approximately 2 weeks.³⁶

Despite the efficacy of endometrial aspiration for the diagnosis of pregnancy location, recent data show that physicians have highly variable approaches to PUL with an hCG plateaued above the discriminatory zone: One-third would first perform endometrial aspiration, while one-third would give methotrexate without further diagnostics.³⁷ Academic physicians were 4 times more likely to recommend endometrial aspiration.³⁷

Presumed EP. Following endometrial aspiration, if pathology does not confirm an intrauterine gestation and the hCG fails to decline by at least 15%, the diagnosis of a presumed EP is made.

For stable patients with neither evidence of intra-abdominal bleeding nor contraindications to methotrexate (such as blood dyscrasias, hepatic or renal insufficiency, active pulmonary or peptic ulcer disease, breastfeeding, or a known intolerance to the medication), methotrexate is recommended for medical management.²⁶ Following screening blood work that includes a complete blood count and liver function and renal function tests, the typical methotrexate dose is 50 mg/m² of body surface area. The single-dose regimen entails checking hCG on the day of methotrexate administration and again on days 4 and 7 thereafter. A minimum decline in hCG of 15% between days 4 and 7 indicates successful treatment; if the hCG decline is below 15%, the patient should receive an additional dose of methotrexate.

There are several published alternative regimens for methotrexate administration, including 2-dose and multidose regimens; the 2-dose protocol (2 doses within 7 days) may be more effective in women with higher hCG (> 3,000 mIU/mL) or known adnexal mass.^26,38

Continue to: Contraindications to methotrexate...

Contraindications to methotrexate. In addition to strict medical contraindications to methotrexate, relative contraindications that indicate a higher risk of methotrexate failure include the presence of fetal cardiac activity, EP mass greater than 4 cm, and serum hCG above 5,000 mIU/mL.²⁶ Because of the potential risk of tubal rupture during medical management, relative contraindications also include patient inability to follow up as an outpatient and patient refusal of blood transfusion.²⁶ Patients with contraindications to methotrexate, hemodynamic instability, ultrasonographic or clinical evidence of EP rupture, or those electing for surgical management may be managed with laparoscopy.¹¹ Discussion of surgical management of EP is beyond the scope of this article.

Follow the hCG level. In patients with a failing IUP or an EP treated with methotrexate or salpingostomy, the hCG level should always be followed until it is negative, usually by weekly measurements once the diagnosis is made. In some cases, the hCG level may plateau after an initial decline, alerting the clinician to failed treatment for a known EP or the need for recategorization of a failed IUP as an EP.

CASE Concluded

The patient’s second and third hCG measurements at 2-day intervals were 1,903 mIU/mL (14% rise) and 2,264 mIU/mL (16% rise). At that point, a repeat transvaginal ultrasonography showed no IUP, adnexal mass, or free fluid. The patient was counseled for outpatient endometrial aspiration, which was performed using manual vacuum aspiration. The serum hCG level on the morning of the procedure was 2,420 mIU/mL. On postprocedure day 1, the serum hCG level fell to 1,615 mIU/mL, a 33% decline. The patient was counseled that this decline in hCG indicated a failing IUP. The final pathologic analysis was returned 3 days later, showing no evidence of trophoblasts and chorionic villi. Regardless, the diagnosis of failing IUP remained given the rapid hCG decline; the tissue from the disrupted failing IUP was likely very scant or simply not drawn into the cannula. Serum hCG levels repeated at weekly intervals revealed ongoing decline, and after 4 weeks, the serum hCG was negative.

In summary

For women diagnosed with PUL, the primary goal is to distinguish an IUP from an EP to reduce the risk of EP rupture through expeditious diagnosis and treatment. In women for whom the pregnancy is desired, distinguishing a viable IUP from a nonviable IUP or an EP is the more specific goal to avoid intervention on a viable IUP (with methotrexate or endometrial aspiration). In women with abnormal hCG trends and indeterminate ultrasonography results (particularly with a serum hCG above the discriminatory zone), outpatient endometrial aspiration is a highly effective way to determine pregnancy location, which dictates further treatment. ●

CASE Woman with bleeding in early pregnancy

A 31-year-old woman (G1P0) presents to the local emergency department (ED) due to bleeding in pregnancy. She reports a prior open appendectomy for ruptured appendix; she denies a history of sexually transmitted infections, smoking, and contraception use. She reports having regular menstrual cycles and trying to conceive with her husband for 18 months without success until now.

The patient reports that the previous week she took a home pregnancy test that was positive; she endorses having dark brown spotting for the past 2 days but denies pain. Based on the date of her last menstrual period, gestational age is estimated to be 5 weeks and 1 day. Her human chorionic gonadotropin (hCG) level is 1,670 mIU/mL. Transvaginal ultrasonography demonstrates a normal uterus with an endometrial thickness of 10 mm, no evidence of an intrauterine pregnancy (IUP), normal adnexa bilaterally, and scant free fluid in the pelvis.

Identifying and evaluating pregnancy of unknown location

A pregnancy of unknown location (PUL) is defined by a positive serum hCG level in the absence of a visualized IUP or ectopic pregnancy (EP) by pelvic ultrasonography.

Because of variations in screening tools and clinical practices between institutions and care settings (for example, EDs versus specialized outpatient offices), the incidence of PUL is difficult to capture. In specialized early pregnancy clinics, the rate is 8% to 10%, whereas in the ED setting, the PUL rate has been reported to be as high as 42%.^1-6 While approximately 98% to 99% of all pregnancies are intrauterine, only 30% of PULs will continue to develop as viable ongoing intrauterine gestations.^7-9 The remainder are revealed as failing IUPs or EPs. To counsel patients, set expectations, and triage to appropriate management, it is critical to diagnose pregnancy location as efficiently as possible.

Ectopic pregnancy

Ectopic pregnancies represent only 1% to 2% of conceptions (both spontaneous and through assisted reproduction) and occur most commonly in the fallopian tube, although EPs also can implant in the cornua of the uterus, the cervix, cesarean scar, and more rarely on the ovary or abdominal viscera.^10,11 Least common, heterotopic pregnancies—in which an IUP coexists with an EP—occur in 1 in 4,000 to 30,000 pregnancies, more commonly in women who used assisted reproduction.¹¹

Major risk factors for EP include a history of tubal surgery, sexually transmitted infections (particularly Chlamydia trachomatis), pelvic inflammatory disease, conception with an intrauterine device in situ, and a history of prior EP or tubal surgery, particularly prior tubal ligation; minor risk factors include a history of infertility (excluding known tubal factor infertility) or smoking (in a dose-dependent manner).^11,12 The concern for an EP is heightened in patients with these risk factors.

Because of the possibility of rupture and life-threatening hemorrhage, EP carries a risk of significant morbidity and mortality.¹³ Ruptured EPs account for approximately 2.7% of all maternal deaths each year.¹⁴ When diagnosed sufficiently early in a stable patient, most EPs can be managed medically with methotrexate, a folic acid antagonist.¹⁵ Ectopic pregnancies also may be managed surgically, and emergency surgery is indicated in women with evidence of EP rupture and intraperitoneal bleeding.

Continue to: Intrauterine pregnancy...

Intrauterine pregnancy

While excluding EP is critical, it is equally important to diagnose an IUP as expeditiously as possible to avoid inadvertent, destructive intervention. Diagnosis and management of a PUL can involve endometrial aspiration, which would interrupt an IUP and should be avoided until the possibility of a viable IUP has been eliminated in desired pregnancies. The inadvertent administration of methotrexate, a known teratogen, to a patient with an undiagnosed viable IUP can result in miscarriage, elective termination, or a live-born infant with significant malformations, all of which expose the administering physician to malpractice litigation.^16,17

In desired pregnancies, it is essential to differentiate between a viable IUP, a nonviable IUP, and an EP to guide appropriate management and ensure patient safety, whereas exclusion of EP is the priority in undesired pregnancies.

Tools for diagnosing pregnancy location

For diagnosing pregnancy location, serial hCG measurement, transvaginal pelvic ultrasonography, and outpatient endometrial aspiration are all relevant clinical tools. Pregnancy location can be diagnosed with either direct visualization of an IUP or EP by ultrasonography or with confirmed pathology (chorionic villi or trophoblast cells) from endometrial aspiration (FIGURE). A decline in hCG to an undetectable level following endometrial aspiration also is considered sufficient to diagnose a failed IUP, even in the absence of a confirmatory ultrasonography.

Trending hCG values

In stable patients with PUL, serum hCG levels are commonly measured at 2-day intervals, ideally for a minimum of 3 values. Conventional wisdom dictates that in viable IUPs, the hCG level should roughly double every 2 days. However, more recent data suggest that the threshold for minimum expected hCG rise for an ongoing IUP should be far lower when the pregnancy is desired.¹⁸ A less conservative cutoff can be considered when a pregnancy is not desired.

In a multisite cohort study of 1,005 women with PUL, a minimum hCG rise of 35% in 2 days captured the majority of IUPs, with a negative predictive value of 97.2% for IUP.¹⁹ Of note, although the cutoff of 35% was selected to reduce the risk of misdiagnosing an IUP as an EP, 7.7% of IUPs (and 16.8% of EPs) were still misclassified, showing that hCG trends must be interpreted in the context of other clinical data, including ultrasonography findings and patient symptoms and history.

A follow-up study demonstrated that hCG rises are lower (but still within this normal range) when the initial hCG value is higher, particularly greater than 3,000 mIU/mL.²⁰

Studies show that the rate of spontaneous hCG decline in failing IUPs ranges from 12% to 47% in 2 days, falling more rapidly from higher starting hCG values.^19,21 In a retrospective review of 443 women with spontaneously resolving PUL (presumed to be failing IUPs), the minimum 2-day decline in hCG was 35%.²² Any spontaneous hCG decline less than 35% in 2 days in a PUL should raise physician concern for EP.

Conversely, EPs do not demonstrate predictable hCG trends and can mimic the hCG trends of viable or failing IUPs. Although typically half of EPs present with an increasing hCG value and half present with a decreasing hCG value, the majority (71%) demonstrate a slower rate of change than either a viable IUP or a miscarriage.¹¹ This slower change (plateau) should heighten the clinician’s suspicion for an EP.

Continue to: Progesterone levels...

Progesterone levels

A progesterone level often is used to attempt to determine pregnancy viability in women who are not receiving progesterone supplementation, although it ultimately has limited utility. While far less sensitive than an hCG value trend, a serum progesterone level of less than 5 to 10 ng/mL is a rough marker of nonviable pregnancy.²³

In a large meta-analysis of women with pain and bleeding, 96.8% of pregnancies with a single progesterone level of less than 10 ng/mL were nonviable.²³ When an inconclusive ultrasonography was documented in addition to symptoms of pain and bleeding, 99.2% of pregnancies with a progesterone level of less than 3.2 to 6 ng/mL were nonviable.

Progesterone’s usefulness in assessing for a PUL is limited: While progesterone levels may indicate nonviability, they provide no indication of pregnancy location (intrauterine or ectopic).

Alternative serologic markers

Various other reproductive and pregnancy-related hormones have been investigated for use in the diagnosis of pregnancy location in PULs, including activin A, inhibin A, pregnancy-associated plasma protein A (PAPP-A), placental-like growth factor, vascular endothelial growth factor, follistatin, and various microRNAs.^24,25 While research into these biomarkers is ongoing, none have been studied in prospective trials, and they are not for use in current clinical care.

Pelvic ultrasonography

Pelvic ultrasonography is a crucial part of PUL assessment. Transvaginal ultrasonography should be interpreted in the context of the estimated gestational age of the pregnancy and serial hCG values, if available; the patient’s symptoms; and the sensitivity of the ultrasonography equipment, which also may be affected by variables that can reduce visualization, such as uterine fibroids and obesity.

The “discriminatory zone” refers to the hCG value above which an IUP should be visualized by ultrasonography. Generally, with an hCG value of 1,500 to 2,000 mIU/mL or greater, an IUP is expected to be seen with transvaginal sonography.^3,26 Many exceptions to the discriminatory zone have been reported, however, including multiple pregnancies, which will have a higher hCG value at an earlier gestational age. Even in singleton pregnancies, viable IUPs have been documented as developing from PULs with an elevated initial hCG value as high as 4,300 mIU/mL.²⁷ The discriminatory zone may vary among clinical hCG assays, and it also is affected by the quality and modernity of the ultrasonography equipment as well as by the ultrasonography operator’s experience and skill.^28,29

The estimated gestational age, based on either the last menstrual period or assisted reproduction procedure, provides a helpful data point to guide expectations for ultrasonography findings.³⁰ Using transvaginal ultrasonography in a normally progressing IUP, a gestational sac—typically measuring 2 to 3 mm—should be visualized at 5 weeks.^15,30 At approximately 5.5 weeks, a yolk sac measuring 3 to 5 mm should appear. At 6 weeks, an embryo with cardiac activity should be visualized.

In a pregnancy reliably dated beyond 5 weeks, the lack of an intrauterine gestational sac is suspicious for, but not diagnostic of, an EP. Conversely, the visualization of a gestational sac alone (without a yolk sac) is insufficient to definitively exclude an EP, since a small fluid collection in the endometrium (a “pseudosac”) can convincingly mimic the appearance of a gestational sac, and a follow-up ultrasonography should be performed in such cases.

Among patients without ultrasonographic evidence of an IUP, endometrial thickness has been posited as a way to differentiate between IUP and EP.^31,32 Evidence suggests that an endometrial stripe of at least 8 to 10 mm may be somewhat predictive of an IUP, while endometrial thickness below 8 mm is more concerning for EP. This clinical variable, however, has been shown repeatedly to lack sufficient sensitivity and specificity for IUP and should be considered only within the entire clinical context.

Continue to: Endometrial aspiration...

Endometrial aspiration

A persistently abnormal hCG trend and an ultrasonography without evidence of an IUP—particularly with an hCG value above the discriminatory zone and/or with reliable pregnancy dating beyond 5 to 6 weeks—is highly concerning for either a failing IUP or an EP. Once a viable desired IUP is excluded beyond reasonable doubt through these measures, endometrial aspiration to determine pregnancy location is a reasonable next step in PUL management.

Endometrial aspiration can identify a failing IUP by detection of trophoblasts or chorionic villi on pathology and/or by a decline of at least 15% in hCG, measured on the day of endometrial aspiration and again the following day. Endometrial aspiration is effective even in clinical care settings that do not have rapid pathologic analysis available, as hCG measurement before and within 24 hours after the procedure still can be performed.

Vacuum aspiration (electric or manual) in an operating room or office setting is an effective tool for diagnosing pregnancy location.^33,34 The use of an endometrial Pipelle for endometrial sampling (typically used for an office endometrial biopsy to diagnose hyperplasia or malignancy) is insufficient for determining pregnancy location.³⁵ For all patients managed with this protocol, the hCG value ideally should be followed until it is undetectable, regardless of whether an EP or failing IUP was diagnosed. In rare cases, an EP may be diagnosed by a late plateau in hCG values, following an initial decline consistent with a failing IUP.

Utility for diagnosis. Retrospective studies in patients with PUL following in vitro fertilization have established the utility of outpatient endometrial aspiration with a Karman cannula, followed by a repeat hCG measurement on the day after the procedure.^34,36 These data demonstrate that between 42% and 69% of women were ultimately diagnosed with a failed IUP following endometrial aspiration, thereby sparing them unnecessary exposure to methotrexate.

A decline in hCG levels of at least 15% within 24 hours after the procedure indicates that a failed IUP is the most likely diagnosis and further intervention is not indicated (although falling hCG values should be monitored for confirmation); confirmatory pathology with chorionic villi or trophoblasts was present in less than half of these women and is not necessary to diagnose a failed IUP.³⁶ Women diagnosed with a failed IUP after endometrial aspiration also benefitted from a shorter time to resolution of the nonviable pregnancy by approximately 2 weeks.³⁶

Despite the efficacy of endometrial aspiration for the diagnosis of pregnancy location, recent data show that physicians have highly variable approaches to PUL with an hCG plateaued above the discriminatory zone: One-third would first perform endometrial aspiration, while one-third would give methotrexate without further diagnostics.³⁷ Academic physicians were 4 times more likely to recommend endometrial aspiration.³⁷

Presumed EP. Following endometrial aspiration, if pathology does not confirm an intrauterine gestation and the hCG fails to decline by at least 15%, the diagnosis of a presumed EP is made.

For stable patients with neither evidence of intra-abdominal bleeding nor contraindications to methotrexate (such as blood dyscrasias, hepatic or renal insufficiency, active pulmonary or peptic ulcer disease, breastfeeding, or a known intolerance to the medication), methotrexate is recommended for medical management.²⁶ Following screening blood work that includes a complete blood count and liver function and renal function tests, the typical methotrexate dose is 50 mg/m² of body surface area. The single-dose regimen entails checking hCG on the day of methotrexate administration and again on days 4 and 7 thereafter. A minimum decline in hCG of 15% between days 4 and 7 indicates successful treatment; if the hCG decline is below 15%, the patient should receive an additional dose of methotrexate.

There are several published alternative regimens for methotrexate administration, including 2-dose and multidose regimens; the 2-dose protocol (2 doses within 7 days) may be more effective in women with higher hCG (> 3,000 mIU/mL) or known adnexal mass.^26,38

Continue to: Contraindications to methotrexate...

Contraindications to methotrexate. In addition to strict medical contraindications to methotrexate, relative contraindications that indicate a higher risk of methotrexate failure include the presence of fetal cardiac activity, EP mass greater than 4 cm, and serum hCG above 5,000 mIU/mL.²⁶ Because of the potential risk of tubal rupture during medical management, relative contraindications also include patient inability to follow up as an outpatient and patient refusal of blood transfusion.²⁶ Patients with contraindications to methotrexate, hemodynamic instability, ultrasonographic or clinical evidence of EP rupture, or those electing for surgical management may be managed with laparoscopy.¹¹ Discussion of surgical management of EP is beyond the scope of this article.

Follow the hCG level. In patients with a failing IUP or an EP treated with methotrexate or salpingostomy, the hCG level should always be followed until it is negative, usually by weekly measurements once the diagnosis is made. In some cases, the hCG level may plateau after an initial decline, alerting the clinician to failed treatment for a known EP or the need for recategorization of a failed IUP as an EP.

CASE Concluded

The patient’s second and third hCG measurements at 2-day intervals were 1,903 mIU/mL (14% rise) and 2,264 mIU/mL (16% rise). At that point, a repeat transvaginal ultrasonography showed no IUP, adnexal mass, or free fluid. The patient was counseled for outpatient endometrial aspiration, which was performed using manual vacuum aspiration. The serum hCG level on the morning of the procedure was 2,420 mIU/mL. On postprocedure day 1, the serum hCG level fell to 1,615 mIU/mL, a 33% decline. The patient was counseled that this decline in hCG indicated a failing IUP. The final pathologic analysis was returned 3 days later, showing no evidence of trophoblasts and chorionic villi. Regardless, the diagnosis of failing IUP remained given the rapid hCG decline; the tissue from the disrupted failing IUP was likely very scant or simply not drawn into the cannula. Serum hCG levels repeated at weekly intervals revealed ongoing decline, and after 4 weeks, the serum hCG was negative.

In summary

For women diagnosed with PUL, the primary goal is to distinguish an IUP from an EP to reduce the risk of EP rupture through expeditious diagnosis and treatment. In women for whom the pregnancy is desired, distinguishing a viable IUP from a nonviable IUP or an EP is the more specific goal to avoid intervention on a viable IUP (with methotrexate or endometrial aspiration). In women with abnormal hCG trends and indeterminate ultrasonography results (particularly with a serum hCG above the discriminatory zone), outpatient endometrial aspiration is a highly effective way to determine pregnancy location, which dictates further treatment. ●

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CASE Black woman in stable labor expresses fear 
 

A 29-year-old Black woman (G1) at 39 0/7 weeks’ gestation presents to your labor and delivery unit reporting leaking fluid and contractions. She is found to have ruptured membranes and reassuring fetal testing. Her cervix is 4 cm dilated, and you recommend admission for expectant management of labor. She is otherwise healthy and has no significant medical history. 

As you are finishing admitting this patient, you ask if she has any remaining questions. She asks quietly, “Am I going to die today?”

You provide reassurance of her stable clinical picture, then pause and ask the patient about her fears. She looks at you and says, “They didn’t believe Serena Williams, so why would they believe me?”

Your patient is referencing Serena Williams’ harrowing and public postpartum course, complicated by a pulmonary embolism and several reoperations.¹ While many of us in the medical field may read this account as a story of challenges with an ultimate triumph, many expectant Black mothers hold Serena’s experience as a cautionary tale about deep-rooted inequities in our health care system that lead to potentially dangerous outcomes. 

Disparities in care 

They are right to be concerned. In the United States, Black mothers are 4 times more likely to die during or after pregnancy, mostly from preventable causes,² and nearly 50% more likely to have a preterm delivery.³ These disparities extend beyond the delivery room to all aspects of ObGyn care. Black women are 2 to 3 times more likely to die from cervical cancer, and they are more likely to be diagnosed at a later stage, thus rendering treatment less effective.⁴ Black patients also have a higher burden of obesity, diabetes, and cardiac disease, and when they present to the hospital, receive evidence-based treatment at lower rates compared with White patients.⁵

Mourning the deaths of Ahmaud Arbery, Breonna Taylor, and George Floyd, amongst the many other Black lives taken unjustly in the United States, has highlighted egregious practices against people of color embedded within the systems meant to protect and serve our communities. We as ObGyn physicians must take professional onus to recognize a devastating but humbling truth—systemic racism has long pervaded our health care practices and systems, and now more than ever, we must do more to stand by and for our patients. 

As ObGyns, we help support patients through some of the happiest, most vulnerable, and potentially most dire moments of their lives. We help patients through the birth of their children, reproductive struggles, gynecologic concerns, and cancer diagnoses. Many of us chose this field for the privilege of caring for patients at these critical moments in their lives, but we have often neglected the racism present in our practices, our hospital settings, and the medical system itself. We often fail to acknowledge our own implicit bias and the role that we play in contributing to acts and experiences of racism that our patients and our colleagues face on a daily basis. 

Racism in our origins 

The history of obstetrics and gynecology shows us a long record of physicians perpetrating injustices that target marginalized communities of color. Dr. James Sims, often given the title of “father of modern gynecology,” performed numerous experiments on unanesthetized Black female slaves to develop procedures for fistulae repair and other surgical techniques.⁶ Throughout the twentieth century, dating as recent as 1979, state laws written in the name of public safety forcibly sterilized women of color to control an “undesirable population.”⁷ When a patient of color declines a method of long-acting reversible contraception, birth control pills, or tubal ligation, do you take the time to reflect on the potential context of the patient’s decision? 

It is critical to recognize the legacy that these acts have on our patients today, leading to a higher burden of disease and an understandable distrust of the medical system. The uncovering of the unethical practices of the National Institutions of Health‒funded Tuskegee syphilis study, in which hundreds of Black men with latent syphilis were passively monitored despite the knowledge of a proven treatment, has attributed to a measurable decrease in life expectancy among Black males.⁸ Even as we face the COVID-19 pandemic, the undercurrent of racism continues to do harm. Black patients are 5 times more likely to be hospitalized with COVID-19 than their White counterparts. This disparity, in part, is a product of a higher burden of comorbidities and the privilege associated with shelter-in-place policies, which disproportionately strain communities of color.⁹

We as a medical community need to do better for our patients. No matter how difficult to confront, each of us must acknowledge our own biases and our duty to combat persistent and perpetual racism in our medical system. We need to commit to amplifying the voices of our Black patients and colleagues. It is not enough to celebrate diversity for performance sake—it is time to recognize that diversity saves lives.

We have a responsibility to rectify these traditions of injustice and work toward a safer, more equitable, healthy future for our patients and their families. While this pledge may seem daunting, changes at individual and systems levels can make a difference for all patients that come through our doors. In addition, to honor our oath to “do no harm,” we must act; Black lives matter, and we are charged as medical providers to help our patients thrive, especially those from historically oppressed communities and who continue to suffer inexcusable injustices in health care and beyond. 

Take action

Here is a collection of ways to institute an antiracist environment and more equitable care for your patients.
 

Self-reflect and educate

• Learn about the role racism plays in ObGyn and modern medicine. One place to start: read “Medical Bondage: Race, Gender and the Origins of American Gynecology” by Deidre Cooper Owens. Also check out articles and key readings curated by the Black Mamas Matter Alliance. 
• Introduce and sustain antiracism training for all staff in your clinic or hospital system. To start, consider taking these free and quick implicit bias tests at a staff or department meeting. 
• Familiarize yourself and your colleagues with facets of reproductive justice—the human right to have children, to not have children, and to nurture children in a safe and healthy environment—and incorporate these values in your practice. Request trainings in reproductive justice from community groups like Sister Song. 
• Sign up for updates for state and national bills addressing health inequity and access to reproductive health services. Show your support by calling your congress-people, testifying, or donating to a cause that promotes these bills.  You can stay up to date on national issues with government affairs newsletters from the American College of Obstetricians and Gynecologists. Sign up here. 
• Continue the conversation and re-evaluate your personal and institution’s efforts to combat racism and social and reproductive injustices. 

Provide access to high-quality reproductive health care

• Ask your patients what barriers they faced to come to your clinic and receive the care they needed. Consider incorporating the following screening tools regarding social determinants of health: PRAPARE screening tool, AAFP screening tool. 
• Promote access to insurance and support programs, including nutrition, exercise and wellness, and safe home and school environments. Look up resources available to your patients by their zip codes using AAFP’s Neighborhood Navigator. 
• Help patients access their medications at affordable prices in their neighborhoods by using free apps. Use the GoodRx app to identify discounts for prescriptions at various pharmacies, and search the Bedsider app to find out how your patients can get their birth control for free and delivered to their homes.
• Expand access to language services for patients who do not speak English as their first language. If working in a resource-limited setting, use the Google Translate app. Print out these free handouts for birth control fact sheets in different languages. 
• Establish standardized protocols for common treatment paradigms to reduce the influence of bias in clinical scenarios. For example, institute a protocol for managing postoperative pain to ensure equal access to treatment. 
• Institute the AIM (Alliance for Innovation on Maternal Health) patient safety bundle on the Reduction of Peripartum Racial/Ethnic Disparities. Learn more about AIM’s maternal safety and quality improvement initiative to reduce maternal morbidity and mortality here. 

Support a diverse workforce

• Designate and/or hire a Diversity and Inclusion Officer at your institution to ensure that hiring practices actively achieve a diverse workforce and that employees feel supported in the work environment. Consider coalition-building between hospitals, like the UPHS-CHOP Alliance of Minority Physicians.
• Recruit diverse applicants by advertising positions to groups that focus on the advancement of underrepresented minorities in medicine. Engage with your local chapter of the National Medical Association and American Medical Women’s Association. 
• Have a system in place for anonymous reporting of incidents involving bias or discrimination against staff, and develop a protocol to ensure action is taken in case of such incidents.
• Institute a recurring conference or Grand Rounds across disciplines to discuss the impacts of bias and discrimination on patients and providers at your institution. View examples of these conferences here.
• Ensure invited speakers and other educational opportunities are comprised of diverse representation.
• Create a work environment with safe spaces for the discussion of racism, discrimination, and bias. 

CASE Black woman in stable labor expresses fear 
 

A 29-year-old Black woman (G1) at 39 0/7 weeks’ gestation presents to your labor and delivery unit reporting leaking fluid and contractions. She is found to have ruptured membranes and reassuring fetal testing. Her cervix is 4 cm dilated, and you recommend admission for expectant management of labor. She is otherwise healthy and has no significant medical history. 

As you are finishing admitting this patient, you ask if she has any remaining questions. She asks quietly, “Am I going to die today?”

You provide reassurance of her stable clinical picture, then pause and ask the patient about her fears. She looks at you and says, “They didn’t believe Serena Williams, so why would they believe me?”

Your patient is referencing Serena Williams’ harrowing and public postpartum course, complicated by a pulmonary embolism and several reoperations.¹ While many of us in the medical field may read this account as a story of challenges with an ultimate triumph, many expectant Black mothers hold Serena’s experience as a cautionary tale about deep-rooted inequities in our health care system that lead to potentially dangerous outcomes. 

Disparities in care 

They are right to be concerned. In the United States, Black mothers are 4 times more likely to die during or after pregnancy, mostly from preventable causes,² and nearly 50% more likely to have a preterm delivery.³ These disparities extend beyond the delivery room to all aspects of ObGyn care. Black women are 2 to 3 times more likely to die from cervical cancer, and they are more likely to be diagnosed at a later stage, thus rendering treatment less effective.⁴ Black patients also have a higher burden of obesity, diabetes, and cardiac disease, and when they present to the hospital, receive evidence-based treatment at lower rates compared with White patients.⁵

Mourning the deaths of Ahmaud Arbery, Breonna Taylor, and George Floyd, amongst the many other Black lives taken unjustly in the United States, has highlighted egregious practices against people of color embedded within the systems meant to protect and serve our communities. We as ObGyn physicians must take professional onus to recognize a devastating but humbling truth—systemic racism has long pervaded our health care practices and systems, and now more than ever, we must do more to stand by and for our patients. 

As ObGyns, we help support patients through some of the happiest, most vulnerable, and potentially most dire moments of their lives. We help patients through the birth of their children, reproductive struggles, gynecologic concerns, and cancer diagnoses. Many of us chose this field for the privilege of caring for patients at these critical moments in their lives, but we have often neglected the racism present in our practices, our hospital settings, and the medical system itself. We often fail to acknowledge our own implicit bias and the role that we play in contributing to acts and experiences of racism that our patients and our colleagues face on a daily basis. 

Racism in our origins 

The history of obstetrics and gynecology shows us a long record of physicians perpetrating injustices that target marginalized communities of color. Dr. James Sims, often given the title of “father of modern gynecology,” performed numerous experiments on unanesthetized Black female slaves to develop procedures for fistulae repair and other surgical techniques.⁶ Throughout the twentieth century, dating as recent as 1979, state laws written in the name of public safety forcibly sterilized women of color to control an “undesirable population.”⁷ When a patient of color declines a method of long-acting reversible contraception, birth control pills, or tubal ligation, do you take the time to reflect on the potential context of the patient’s decision? 

It is critical to recognize the legacy that these acts have on our patients today, leading to a higher burden of disease and an understandable distrust of the medical system. The uncovering of the unethical practices of the National Institutions of Health‒funded Tuskegee syphilis study, in which hundreds of Black men with latent syphilis were passively monitored despite the knowledge of a proven treatment, has attributed to a measurable decrease in life expectancy among Black males.⁸ Even as we face the COVID-19 pandemic, the undercurrent of racism continues to do harm. Black patients are 5 times more likely to be hospitalized with COVID-19 than their White counterparts. This disparity, in part, is a product of a higher burden of comorbidities and the privilege associated with shelter-in-place policies, which disproportionately strain communities of color.⁹

We as a medical community need to do better for our patients. No matter how difficult to confront, each of us must acknowledge our own biases and our duty to combat persistent and perpetual racism in our medical system. We need to commit to amplifying the voices of our Black patients and colleagues. It is not enough to celebrate diversity for performance sake—it is time to recognize that diversity saves lives.

We have a responsibility to rectify these traditions of injustice and work toward a safer, more equitable, healthy future for our patients and their families. While this pledge may seem daunting, changes at individual and systems levels can make a difference for all patients that come through our doors. In addition, to honor our oath to “do no harm,” we must act; Black lives matter, and we are charged as medical providers to help our patients thrive, especially those from historically oppressed communities and who continue to suffer inexcusable injustices in health care and beyond. 

Take action

Here is a collection of ways to institute an antiracist environment and more equitable care for your patients.
 

Self-reflect and educate

• Learn about the role racism plays in ObGyn and modern medicine. One place to start: read “Medical Bondage: Race, Gender and the Origins of American Gynecology” by Deidre Cooper Owens. Also check out articles and key readings curated by the Black Mamas Matter Alliance. 
• Introduce and sustain antiracism training for all staff in your clinic or hospital system. To start, consider taking these free and quick implicit bias tests at a staff or department meeting. 
• Familiarize yourself and your colleagues with facets of reproductive justice—the human right to have children, to not have children, and to nurture children in a safe and healthy environment—and incorporate these values in your practice. Request trainings in reproductive justice from community groups like Sister Song. 
• Sign up for updates for state and national bills addressing health inequity and access to reproductive health services. Show your support by calling your congress-people, testifying, or donating to a cause that promotes these bills.  You can stay up to date on national issues with government affairs newsletters from the American College of Obstetricians and Gynecologists. Sign up here. 
• Continue the conversation and re-evaluate your personal and institution’s efforts to combat racism and social and reproductive injustices. 

Provide access to high-quality reproductive health care

• Ask your patients what barriers they faced to come to your clinic and receive the care they needed. Consider incorporating the following screening tools regarding social determinants of health: PRAPARE screening tool, AAFP screening tool. 
• Promote access to insurance and support programs, including nutrition, exercise and wellness, and safe home and school environments. Look up resources available to your patients by their zip codes using AAFP’s Neighborhood Navigator. 
• Help patients access their medications at affordable prices in their neighborhoods by using free apps. Use the GoodRx app to identify discounts for prescriptions at various pharmacies, and search the Bedsider app to find out how your patients can get their birth control for free and delivered to their homes.
• Expand access to language services for patients who do not speak English as their first language. If working in a resource-limited setting, use the Google Translate app. Print out these free handouts for birth control fact sheets in different languages. 
• Establish standardized protocols for common treatment paradigms to reduce the influence of bias in clinical scenarios. For example, institute a protocol for managing postoperative pain to ensure equal access to treatment. 
• Institute the AIM (Alliance for Innovation on Maternal Health) patient safety bundle on the Reduction of Peripartum Racial/Ethnic Disparities. Learn more about AIM’s maternal safety and quality improvement initiative to reduce maternal morbidity and mortality here. 

Support a diverse workforce

• Designate and/or hire a Diversity and Inclusion Officer at your institution to ensure that hiring practices actively achieve a diverse workforce and that employees feel supported in the work environment. Consider coalition-building between hospitals, like the UPHS-CHOP Alliance of Minority Physicians.
• Recruit diverse applicants by advertising positions to groups that focus on the advancement of underrepresented minorities in medicine. Engage with your local chapter of the National Medical Association and American Medical Women’s Association. 
• Have a system in place for anonymous reporting of incidents involving bias or discrimination against staff, and develop a protocol to ensure action is taken in case of such incidents.
• Institute a recurring conference or Grand Rounds across disciplines to discuss the impacts of bias and discrimination on patients and providers at your institution. View examples of these conferences here.
• Ensure invited speakers and other educational opportunities are comprised of diverse representation.
• Create a work environment with safe spaces for the discussion of racism, discrimination, and bias. 

CASE Black woman in stable labor expresses fear 
 

A 29-year-old Black woman (G1) at 39 0/7 weeks’ gestation presents to your labor and delivery unit reporting leaking fluid and contractions. She is found to have ruptured membranes and reassuring fetal testing. Her cervix is 4 cm dilated, and you recommend admission for expectant management of labor. She is otherwise healthy and has no significant medical history. 

As you are finishing admitting this patient, you ask if she has any remaining questions. She asks quietly, “Am I going to die today?”

You provide reassurance of her stable clinical picture, then pause and ask the patient about her fears. She looks at you and says, “They didn’t believe Serena Williams, so why would they believe me?”

Your patient is referencing Serena Williams’ harrowing and public postpartum course, complicated by a pulmonary embolism and several reoperations.¹ While many of us in the medical field may read this account as a story of challenges with an ultimate triumph, many expectant Black mothers hold Serena’s experience as a cautionary tale about deep-rooted inequities in our health care system that lead to potentially dangerous outcomes. 

Disparities in care 

They are right to be concerned. In the United States, Black mothers are 4 times more likely to die during or after pregnancy, mostly from preventable causes,² and nearly 50% more likely to have a preterm delivery.³ These disparities extend beyond the delivery room to all aspects of ObGyn care. Black women are 2 to 3 times more likely to die from cervical cancer, and they are more likely to be diagnosed at a later stage, thus rendering treatment less effective.⁴ Black patients also have a higher burden of obesity, diabetes, and cardiac disease, and when they present to the hospital, receive evidence-based treatment at lower rates compared with White patients.⁵

Mourning the deaths of Ahmaud Arbery, Breonna Taylor, and George Floyd, amongst the many other Black lives taken unjustly in the United States, has highlighted egregious practices against people of color embedded within the systems meant to protect and serve our communities. We as ObGyn physicians must take professional onus to recognize a devastating but humbling truth—systemic racism has long pervaded our health care practices and systems, and now more than ever, we must do more to stand by and for our patients. 

As ObGyns, we help support patients through some of the happiest, most vulnerable, and potentially most dire moments of their lives. We help patients through the birth of their children, reproductive struggles, gynecologic concerns, and cancer diagnoses. Many of us chose this field for the privilege of caring for patients at these critical moments in their lives, but we have often neglected the racism present in our practices, our hospital settings, and the medical system itself. We often fail to acknowledge our own implicit bias and the role that we play in contributing to acts and experiences of racism that our patients and our colleagues face on a daily basis. 

Racism in our origins 

The history of obstetrics and gynecology shows us a long record of physicians perpetrating injustices that target marginalized communities of color. Dr. James Sims, often given the title of “father of modern gynecology,” performed numerous experiments on unanesthetized Black female slaves to develop procedures for fistulae repair and other surgical techniques.⁶ Throughout the twentieth century, dating as recent as 1979, state laws written in the name of public safety forcibly sterilized women of color to control an “undesirable population.”⁷ When a patient of color declines a method of long-acting reversible contraception, birth control pills, or tubal ligation, do you take the time to reflect on the potential context of the patient’s decision? 

It is critical to recognize the legacy that these acts have on our patients today, leading to a higher burden of disease and an understandable distrust of the medical system. The uncovering of the unethical practices of the National Institutions of Health‒funded Tuskegee syphilis study, in which hundreds of Black men with latent syphilis were passively monitored despite the knowledge of a proven treatment, has attributed to a measurable decrease in life expectancy among Black males.⁸ Even as we face the COVID-19 pandemic, the undercurrent of racism continues to do harm. Black patients are 5 times more likely to be hospitalized with COVID-19 than their White counterparts. This disparity, in part, is a product of a higher burden of comorbidities and the privilege associated with shelter-in-place policies, which disproportionately strain communities of color.⁹

We as a medical community need to do better for our patients. No matter how difficult to confront, each of us must acknowledge our own biases and our duty to combat persistent and perpetual racism in our medical system. We need to commit to amplifying the voices of our Black patients and colleagues. It is not enough to celebrate diversity for performance sake—it is time to recognize that diversity saves lives.

We have a responsibility to rectify these traditions of injustice and work toward a safer, more equitable, healthy future for our patients and their families. While this pledge may seem daunting, changes at individual and systems levels can make a difference for all patients that come through our doors. In addition, to honor our oath to “do no harm,” we must act; Black lives matter, and we are charged as medical providers to help our patients thrive, especially those from historically oppressed communities and who continue to suffer inexcusable injustices in health care and beyond. 

Take action

Here is a collection of ways to institute an antiracist environment and more equitable care for your patients.
 

Self-reflect and educate

• Learn about the role racism plays in ObGyn and modern medicine. One place to start: read “Medical Bondage: Race, Gender and the Origins of American Gynecology” by Deidre Cooper Owens. Also check out articles and key readings curated by the Black Mamas Matter Alliance. 
• Introduce and sustain antiracism training for all staff in your clinic or hospital system. To start, consider taking these free and quick implicit bias tests at a staff or department meeting. 
• Familiarize yourself and your colleagues with facets of reproductive justice—the human right to have children, to not have children, and to nurture children in a safe and healthy environment—and incorporate these values in your practice. Request trainings in reproductive justice from community groups like Sister Song. 
• Sign up for updates for state and national bills addressing health inequity and access to reproductive health services. Show your support by calling your congress-people, testifying, or donating to a cause that promotes these bills.  You can stay up to date on national issues with government affairs newsletters from the American College of Obstetricians and Gynecologists. Sign up here. 
• Continue the conversation and re-evaluate your personal and institution’s efforts to combat racism and social and reproductive injustices. 

Provide access to high-quality reproductive health care

• Ask your patients what barriers they faced to come to your clinic and receive the care they needed. Consider incorporating the following screening tools regarding social determinants of health: PRAPARE screening tool, AAFP screening tool. 
• Promote access to insurance and support programs, including nutrition, exercise and wellness, and safe home and school environments. Look up resources available to your patients by their zip codes using AAFP’s Neighborhood Navigator. 
• Help patients access their medications at affordable prices in their neighborhoods by using free apps. Use the GoodRx app to identify discounts for prescriptions at various pharmacies, and search the Bedsider app to find out how your patients can get their birth control for free and delivered to their homes.
• Expand access to language services for patients who do not speak English as their first language. If working in a resource-limited setting, use the Google Translate app. Print out these free handouts for birth control fact sheets in different languages. 
• Establish standardized protocols for common treatment paradigms to reduce the influence of bias in clinical scenarios. For example, institute a protocol for managing postoperative pain to ensure equal access to treatment. 
• Institute the AIM (Alliance for Innovation on Maternal Health) patient safety bundle on the Reduction of Peripartum Racial/Ethnic Disparities. Learn more about AIM’s maternal safety and quality improvement initiative to reduce maternal morbidity and mortality here. 

Support a diverse workforce

• Designate and/or hire a Diversity and Inclusion Officer at your institution to ensure that hiring practices actively achieve a diverse workforce and that employees feel supported in the work environment. Consider coalition-building between hospitals, like the UPHS-CHOP Alliance of Minority Physicians.
• Recruit diverse applicants by advertising positions to groups that focus on the advancement of underrepresented minorities in medicine. Engage with your local chapter of the National Medical Association and American Medical Women’s Association. 
• Have a system in place for anonymous reporting of incidents involving bias or discrimination against staff, and develop a protocol to ensure action is taken in case of such incidents.
• Institute a recurring conference or Grand Rounds across disciplines to discuss the impacts of bias and discrimination on patients and providers at your institution. View examples of these conferences here.
• Ensure invited speakers and other educational opportunities are comprised of diverse representation.
• Create a work environment with safe spaces for the discussion of racism, discrimination, and bias. 

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

CASE Woman with vulvar itch and white vaginal discharge

A 26-year-old sexually active nulligravid woman requests evaluation for moderately intense “itching in the vagina and on the vulva.” She uses combination oral contraceptives and has 2 current sexual partners. On physical examination, you note a thick, white, curd-like discharge that is adherent to the vaginal epithelium. The vulva is erythematous, and small “satellite lesions” are evident in the intertriginous folds.

• What is the most likely diagnosis?
• How should you treat this patient?

Approximately 75% of all women will have at least 1 episode of vulvovaginal candidiasis (VVC) in their lifetime.¹ Candida albicans, the most commonly identified organism in these infections, colonizes the vagina of many individuals commensally; higher rates of colonization occur in women with diabetes, obesity, recent use of broad-spectrum antibiotics, steroid use and immunosuppression, and in women who are pregnant. Of special interest, pregnant women have an increased risk of symptomatic infection, and they respond less favorably to conventional treatment regimens.¹

Deconstructing C albicans and other species

Historically, in more than 90% of cases, C albicans is the principal cause of VVC. While it remains the most prevalent Candida species in the United States, over the last 15 years studies have demonstrated that in some countries, such as India and Nigeria, C albicans constitutes less than half of the cultured species in women with VVC. This observation may be due to the widespread availability and use of common antifungal medications, which leads to resistance and selection for resistant species.^1,2

In asymptomatic women, vaginal colonies of C albicans grow in the yeast form. This condition is usually well tolerated by the host and does not cause a major immune response. In periods of stress for the host micro- and mycobiomes, however (dysbiosis, immune suppression, trauma), C albicans is induced into morphogenesis, proliferating and forming hyphae that are thought to activate the host immune response. The vaginal epithelium becomes sensitized to the presence of C albicans and recruits large numbers of neutrophils that, in turn, drive the pathophysiology of VVC.³

There is a theory that the separation of the urethra and anus by the vagina has exerted evolutionary pressure to maintain the presence of commensal C albicans yeast colonies in the vagina. C albicans exerts an antagonistic effect on many bacteria and, therefore, may act as a “microbiologic barrier” between the anus and the urethra to prevent urinary tract infections that, before the modern antibiotic era, may have caused serious morbidity and even mortality.³

Other organisms that cause VVC include C glabrata, C parapsilosis, and C tropicalis. Ex vivo experiments have shown that co-infection of C albicans with C glabrata enhances the ability of C glabrata to invade tissue.² C glabrata is more frequently resistant to commonly used antifungal compounds than C albicans,^2,4 which suggests that identifying the specific fungal pathogen is becoming increasingly important in planning targeted therapy.

Continue to: A common infection...

A common infection

While three-quarters of women will experience VVC at least once in their lifetime, between 40% and 45% will experience it more than once, and 5% to 8% will develop recurrent VVC. Among pregnant women, 15% will develop symptomatic VVC.^1,2

However, because VVC is not a reportable disease and antifungal medication is available over the counter without physician consultation, these numbers likely underestimate the true incidence of the infection.⁴

Complications in pregnancy

Vaginal infections, including VVC, bacterial vaginosis (BV), and trichomoniasis, may be associated with 40% of preterm deliveries.⁵ The high concentrations of estrogen and progesterone during pregnancy create a uniquely glycogen-rich vaginal environment in which Candida species can flourish.^2,4 Even asymptomatic colonization of the vagina with Candida species has been associated with preterm labor, preterm birth, and low birth weight.^1,6 This association appears to have more severe consequences if VVC occurs in the second trimester compared with the first trimester.⁶

Additionally, congenital candidiasis of the newborn may result from intrauterine Candida infection or heavy maternal vaginal colonization at delivery, and the infection is evident within 24 hours of birth. It presents typically as oropharyngeal candidiasis (thrush) of the newborn.¹

Clinical manifestations of infection

The classic manifestations of Candida infection are similar in both the pregnant and nonpregnant patient: acute vaginal and vulvar pruritus and thick, white, malodorous “cottage cheese” vaginal discharge.^1,4 Exercise caution, however, in treating presumptively based on these symptoms alone, especially in pregnancy, because they are not specific to candidiasis.⁴ Vaginal discharge is not always present, and it may vary in appearance and odor. Pruritus is the most specific symptom of Candida infection, but studies show that it is an accurate predictor in only 38% of cases.⁷

Other common signs and symptoms include the sensation of burning, dysuria, dyspareunia, fissures, excoriations, and pruritus ani. Physical examination demonstrates erythema and swelling of labial, vulvar, and vaginal structures, with a normal cervix and an adherent white or off-white discharge. When the discharge is removed from the vaginal wall, small bleeding points may appear.^1,4

Making the diagnosis

As mentioned, history alone is not sufficient to make a definitive diagnosis of candidiasis. The diagnosis should be made by examining vaginal secretions under a microscope or by culture.⁴ A wet mount and KOH (potassium hydroxide) prep help differentiate VVC, BV, and trichomoniasis. Culture is particularly valuable in identifying less common fungal organisms, such as C glabrata and C tropicalis.

Vaginal pH testing is not conclusive for Candida because vaginal pH is normal in VVC. However, pH assessment can rule in other causative organisms if the value is abnormal (that is, elevated pH of 4.5 or greater with BV and trichomoniasis).¹

Treatment options

Acute infection. A pregnant woman who tests positive for VVC may safely be treated in any trimester with a 7-day course of a topical azole.⁸ If the patient prefers the convenience of oral therapy, after the first trimester, oral fluconazole, 150 mg on day 1 and day 3, may be used for treatment. Note that fluconazole has been associated with an increased risk of spontaneous abortion and cardiac septal defects when used in the first trimester.¹

The Centers for Disease Control and Prevention recommends a number of topical treatments for VVC (TABLE).⁸ Several of these drugs are available over the counter without a prescription. Topical azoles are more effective than nystatin in treating VVC, and posttreatment cultures are negative in up to 90% of treated patients.⁸

Recurrent infections. Recurrent VVC is defined as 4 or more episodes of symptomatic VVC within 12 months.⁸ Typical first-line treatment of recurrent infections in nonpregnant patients is a 6-month course of fluconazole, 150 mg weekly.^9,10 As noted, however, fluconazole should not be used in the first trimester of pregnancy. It is acceptable therapy thereafter for patients who have troublesome recurrent or persistent infections.

Continue to: Strategies for preventing recurrence...

Strategies for preventing recurrence

While it is logical to consider antimycotic prophylaxis in women with a history of recurring VVC and/or a significant number of known risk factors, data suggest that extended prophylaxis with an azole does not consistently achieve long-term elimination of vaginal Candida organisms after cessation of the azole.⁹

At-risk women should be counseled to make lifestyle adjustments, such as wearing breathable cotton clothing, particularly undergarments; promptly changing out of damp clothing; and forgoing the use of commercial intravaginal feminine hygiene products.

Recent research has shown that the use of Saccharomyces cerevisiae–based probiotics has promise for controlling the burden of C albicans in women receiving antifungal drugs for VVC and also for preventing recurrence; however, this approach has undergone limited testing in humans, and its efficacy and safety in pregnancy is unknown.¹¹ ●

The destructive toll COVID-19 has caused worldwide is devastating. In the United States, the disproportionate deaths of Black, Indigenous, and Latinx people due to structural racism, amplified by economic adversity, is unacceptable. Meanwhile, the continued murder of Black people by those sworn to protect the public is abhorrent and can no longer be ignored. Black lives matter. These crises have rightly gripped our attention, and should galvanize physicians individually and collectively to use our privileged voices and relative power for justice. We must strive for engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.

The COVID-19 pandemic has illuminated the vast inequities in our country. It has highlighted the continued poor outcomes our health and health care systems create for Black, Indigenous, and Latinx communities. It also has demonstrated clearly that we are all connected—one large community, interdependent yet rife with differential power, privilege, and oppression. We must address these racial disparities—not only in the name of justice and good health for all but also because it is a moral and ethical imperative for us as physicians—and SARS-CoV-2 clearly shows us that it is in the best interest of everyone to do so.

First step: A deep dive look at systemic racism

What is first needed is an examination and acknowledgement by medicine and health care at large of the deeply entrenched roots of systemic and institutional racism in our profession and care systems, and their disproportionate and unjust impact on the health and livelihood of communities of color. The COVID-19 pandemic is only a recent example that highlights the perpetuation of a system that harms people of color. Racism, sexism, gender discrimination, economic and social injustice, religious persecution, and violence against women and children are age-old. We have yet to see health care institutions implement system-wide intersectional and antiracist practices to address them. Mandatory implicit bias training, policies for inclusion and diversity, and position statements are necessary first steps; however, they are not a panacea. They are insufficient to create the bold changes we need. The time for words has long passed. It is time to listen, to hear the cries of anguish and outrage, to examine our privileged position, to embrace change and discomfort, and most importantly to act, and to lead in dismantling the structures around us that perpetuate racial inequity.

How can we, as physicians and leaders, join in action and make an impact?

Dr. Camara Jones, past president of the American Public Health Association, describes 3 levels of racism:

• structural or systemic
• individual or personally mediated
• internalized.

Interventions at each level are important if we are to promote equity in health and health care. This framework can help us think about the following strategic initiatives.

Continue to: 1. Commit to becoming an antiracist and engage in independent study...

1. Commit to becoming antiracist and engage in independent study. This is an important first step as it will form the foundations for interventions—one cannot facilitate change without understanding the matter at hand. This step also may be the most personally challenging step forcing all of us to wrestle with discomfort, sadness, fear, guilt, and a host of other emotional responses. Remember that great change has never been born out of comfort, and the discomfort physicians may experience while unlearning racism and learning antiracism pales in comparison to what communities of color experience daily. We must actively work to unlearn the racist and anti-Black culture that is so deeply woven into every aspect of our existence.

Learn the history that was not given to us as kids in school. Read the brilliant literary works of Black, Indigenous, and Latinx artists and scholars on dismantling racism. Expand our vocabulary and knowledge of core concepts in racism, racial justice, and equity. Examine and reflect on our day-to-day practices. Be vocal in our commitment to antiracism—the time has passed for staying silent. If you are white, facilitate conversations about race with your white colleagues; the inherent power of racism relegates it to an issue that can never be on the table, but it is time to dismantle that power. Learn what acts of meaningful and intentional alliances are and when we need to give up power or privilege to a person of color. We also need to recognize that we as physicians, while leaders in many spaces, are not leaders in the powerful racial justice grassroots movements. We should learn from these movements, follow their lead, and use our privilege to uplift racial justice in our settings.

2. Embrace the current complexities with empathy and humility, finding ways to exercise our civic responsibility to the public with compassion. During the COVID-19 pandemic we have seen the devastation that social isolation, job loss, and illness can create. Suddenly those who could never have imagined themselves without food are waiting hours in their cars for food bank donations or are finding empty shelves in stores. Those who were not safe at home were suddenly imprisoned indefinitely in unsafe situations. Those who were comfortable, well-insured, and healthy are facing an invisible health threat, insecurity, fear, anxiety, and loss. Additionally, our civic institutions are failing. Those of us who always took our right to vote for granted are being forced to stand in hours’-long lines to exercise that right; while those who have been systematically disenfranchised are enduring even greater threats to their constitutional right to exercise their political power, disallowing them to speak for their families and communities and to vote for the justice they deserve. This may be an opportunity to stop blaming victims and recognize the toll that structural and systemic contributions to inequity have created over generations.

3. Meaningfully engage with and advocate for patients. In health and health care, we must begin to engage with the communities we serve and truly listen to their needs, desires, and barriers to care, and respond accordingly. Policies that try to address the social determinants of health without that engagement, and without the acknowledgement of the structural issues that cause them, however well-intentioned, are unlikely to accomplish their goals. We need to advocate as physicians and leaders in our settings for every policy, practice, and procedure to be scrutinized using an antiracist lens. To execute this, we need to:

• ask why clinic and hospital practices are built the way they are and how to make them more reflexive and responsive to individual patient’s needs
• examine what the disproportionate impacts might be on different groups of patients from a systems-level
• be ready to dismantle and/or rebuild something that is exacerbating disparate outcomes and experiences
• advocate for change that is built upon the narratives of patients and their communities.

We should include patients in the creation of hospital policies and guidelines in order to shift power toward them and to be transparent about how the system operates in order to facilitate trust and collaboration that centers patients and communities in the systems created to serve them.

Continue to: 4. Intentionally repair and build trust...

4. Intentionally repair and build trust. To create a safe environment, we must repair what we have broken and earn the trust of communities by uplifting their voices and redistributing our power to them in changing the systems and structures that have, for generations, kept Black, Indigenous, and Latinx people oppressed. Building trust requires first owning our histories of colonization, genocide, and slavery—now turned mass incarceration, debasement, and exploitation—that has existed for centuries. We as physicians need to do an honest examination of how we have eroded the trust of the very communities we care for since our profession’s creation. We need to acknowledge, as a white-dominant profession, the medical experimentation on and exploitation of Black and Brown bodies, and how this formed the foundation for a very valid deep distrust and fear of the medical establishment. We need to recognize how our inherent racial biases continue to feed this distrust, like when we don’t treat patients’ pain adequately or make them feel like we believe and listen to their needs and concerns. We must acknowledge our complicity in perpetuating the racial inequities in health, again highlighted by the COVID-19 pandemic.

5. Increase Black, Indigenous, and Latinx representation in physician and other health care professions’ workforce. Racism impacts not only patients but also our colleagues of color. The lack of racial diversity is a symptom of racism and a representation of the continued exclusion and devaluing of physicians of color. We must recognize this legacy of exclusion and facilitate intentional recruitment, retention, inclusion, and belonging of people of color into our workforce. Tokenism, the act of symbolically including one or few people from underrepresented groups, has been a weapon used by our workforce against physicians of color, resulting in isolation, “othering,” demoralization, and other deleterious impacts. We need to reverse this history and diversify our training programs and workforce to ensure justice in our own community.

6. Design multifaceted interventions. Multilevel problems require multilevel solutions. Interventions targeted solely at one level, while helpful, are unlikely to result in the larger scale changes our society needs to implement if we are to eradicate the impact of racism on health. We have long known that it is not just “preexisting conditions” or “poor” individual behaviors that lead to negative and disparate health outcomes—these are impacted by social and structural determinants much larger and more deleterious than that. It is critically important that we allocate and redistribute resources to create safe and affordable housing; childcare and preschool facilities; healthy, available, and affordable food; equitable and affordable educational opportunities; and a clean environment to support the health of all communities—not only those with the highest tax base. It is imperative that we strive to understand the lives of our fellow human beings who have been subjected to intergenerational social injustices and oppressions that have continued to place them at the margins of society. We need to center the lived experiences of communities of color in the design of multilevel interventions, especially Black and Indigenous communities. While we as physicians cannot individually impact education, economic, or food/environment systems, we can use our power to advocate for providing resources for the patients we care for and can create strategies within the health care system to address these needs in order to achieve optimal health. Robust and equitable social structures are the foundations for health, and ensuring equitable access to them is critical to reducing disparities.

Commit to lead

We must commit to unlearning our internalized racism, rebuilding relationships with communities of color, and engaging in antiracist practices. As a profession dedicated to healing, we have an obligation to be leaders in advocating for these changes, and dismantling the inequitable structure of our health care system.

Our challenge now is to articulate solutions. While antiracism should be informed by the lived experiences of communities of color, the work of antiracism is not their responsibility. In fact, it is the responsibility of our white-dominated systems and institutions to change.

There are some solutions that are easier to enumerate because they have easily measurable outcomes or activities, such as:

• collecting data transparently
• identifying inequities in access, treatment, and care
• conducting rigorous root cause analysis of those barriers to care
• increasing diverse racial and gender representation on decision-making bodies, from board rooms to committees, from leadership teams to research participants
• redistribute power by paving the way for underrepresented colleagues to participate in clinical, administrative, educational, executive, and health policy spaces
• mentoring new leaders who come from marginalized communities.

Every patient deserves our expertise and access to high-quality care. We should review our patient panels to ensure we are taking steps personally to be just and eliminate disparities, and we should monitor the results of those efforts.

Continue to: Be open to solutions that may make us “uncomfortable”...

Be open to solutions that may make us “uncomfortable”

There are other solutions, perhaps those that would be more effective on a larger scale, which may be harder to measure using our traditional ways of inquiry or measurement. Solutions that may create discomfort, anger, or fear for those who have held their power or positions for a long time. We need to begin to engage in developing, cultivating, and valuing innovative strategies that produce equally valid knowledge, evidence, and solutions without engaging in a randomized controlled trial. We need to reinvent the way inquiry, investigation, and implementation are done, and utilize novel, justice-informed strategies that include real-world evidence to produce results that are applicable to all (not just those willing to participate in sponsored trials). Only then will we be able to provide equitable health outcomes for all.

We also must accept responsibility for the past and humbly ask communities to work with us as we struggle to eliminate racism and dehumanization of Black lives by calling out our actions or inaction, recognizing the impact of our privileged status, and stepping down or stepping aside to allow others to lead. Sometimes it is as simple as turning off the Zoom camera so others can talk. By redistributing power and focusing this work upon the narratives of marginalized communities, we can improve our system for everyone. We must lead with action within our practices and systems; become advocates within our communities, institutions, and profession; strategize and organize interventions at both structural and individual levels to first recognize and name—then change—the systems; and unlearn behaviors that perpetuate racism.

Inaction is shirking our responsibility among the medical community

Benign inaction and unintentional acquiescence with “the way things are and have always been” abdicates our responsibility as physicians to improve the health of our patients and our communities. The modern Hippocratic Oath reminds us: “I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.” We have a professional and ethical responsibility to ensure health equity, and thus racial equity. As physicians, as healers, as leaders we must address racial inequities at all levels as we commit to improving the health of our nation. We can no longer stand silent in the face of the violence, brutality, and injustices our patients, friends, family, neighbors, communities, and society as a whole live through daily. It is unjust and inhumane to do so.

To be silent is to be complicit. As Gandhi said so long ago, we must “be the change we wish to see in the world.” And as Ijeoma Olua teaches us, “Anti-racism is the commitment to fight racism wherever you find it, including in yourself. And it’s the only way forward.”
 

The destructive toll COVID-19 has caused worldwide is devastating. In the United States, the disproportionate deaths of Black, Indigenous, and Latinx people due to structural racism, amplified by economic adversity, is unacceptable. Meanwhile, the continued murder of Black people by those sworn to protect the public is abhorrent and can no longer be ignored. Black lives matter. These crises have rightly gripped our attention, and should galvanize physicians individually and collectively to use our privileged voices and relative power for justice. We must strive for engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.

The COVID-19 pandemic has illuminated the vast inequities in our country. It has highlighted the continued poor outcomes our health and health care systems create for Black, Indigenous, and Latinx communities. It also has demonstrated clearly that we are all connected—one large community, interdependent yet rife with differential power, privilege, and oppression. We must address these racial disparities—not only in the name of justice and good health for all but also because it is a moral and ethical imperative for us as physicians—and SARS-CoV-2 clearly shows us that it is in the best interest of everyone to do so.

First step: A deep dive look at systemic racism

What is first needed is an examination and acknowledgement by medicine and health care at large of the deeply entrenched roots of systemic and institutional racism in our profession and care systems, and their disproportionate and unjust impact on the health and livelihood of communities of color. The COVID-19 pandemic is only a recent example that highlights the perpetuation of a system that harms people of color. Racism, sexism, gender discrimination, economic and social injustice, religious persecution, and violence against women and children are age-old. We have yet to see health care institutions implement system-wide intersectional and antiracist practices to address them. Mandatory implicit bias training, policies for inclusion and diversity, and position statements are necessary first steps; however, they are not a panacea. They are insufficient to create the bold changes we need. The time for words has long passed. It is time to listen, to hear the cries of anguish and outrage, to examine our privileged position, to embrace change and discomfort, and most importantly to act, and to lead in dismantling the structures around us that perpetuate racial inequity.

How can we, as physicians and leaders, join in action and make an impact?

Dr. Camara Jones, past president of the American Public Health Association, describes 3 levels of racism:

• structural or systemic
• individual or personally mediated
• internalized.

Interventions at each level are important if we are to promote equity in health and health care. This framework can help us think about the following strategic initiatives.

Continue to: 1. Commit to becoming an antiracist and engage in independent study...

1. Commit to becoming antiracist and engage in independent study. This is an important first step as it will form the foundations for interventions—one cannot facilitate change without understanding the matter at hand. This step also may be the most personally challenging step forcing all of us to wrestle with discomfort, sadness, fear, guilt, and a host of other emotional responses. Remember that great change has never been born out of comfort, and the discomfort physicians may experience while unlearning racism and learning antiracism pales in comparison to what communities of color experience daily. We must actively work to unlearn the racist and anti-Black culture that is so deeply woven into every aspect of our existence.

Learn the history that was not given to us as kids in school. Read the brilliant literary works of Black, Indigenous, and Latinx artists and scholars on dismantling racism. Expand our vocabulary and knowledge of core concepts in racism, racial justice, and equity. Examine and reflect on our day-to-day practices. Be vocal in our commitment to antiracism—the time has passed for staying silent. If you are white, facilitate conversations about race with your white colleagues; the inherent power of racism relegates it to an issue that can never be on the table, but it is time to dismantle that power. Learn what acts of meaningful and intentional alliances are and when we need to give up power or privilege to a person of color. We also need to recognize that we as physicians, while leaders in many spaces, are not leaders in the powerful racial justice grassroots movements. We should learn from these movements, follow their lead, and use our privilege to uplift racial justice in our settings.

2. Embrace the current complexities with empathy and humility, finding ways to exercise our civic responsibility to the public with compassion. During the COVID-19 pandemic we have seen the devastation that social isolation, job loss, and illness can create. Suddenly those who could never have imagined themselves without food are waiting hours in their cars for food bank donations or are finding empty shelves in stores. Those who were not safe at home were suddenly imprisoned indefinitely in unsafe situations. Those who were comfortable, well-insured, and healthy are facing an invisible health threat, insecurity, fear, anxiety, and loss. Additionally, our civic institutions are failing. Those of us who always took our right to vote for granted are being forced to stand in hours’-long lines to exercise that right; while those who have been systematically disenfranchised are enduring even greater threats to their constitutional right to exercise their political power, disallowing them to speak for their families and communities and to vote for the justice they deserve. This may be an opportunity to stop blaming victims and recognize the toll that structural and systemic contributions to inequity have created over generations.

3. Meaningfully engage with and advocate for patients. In health and health care, we must begin to engage with the communities we serve and truly listen to their needs, desires, and barriers to care, and respond accordingly. Policies that try to address the social determinants of health without that engagement, and without the acknowledgement of the structural issues that cause them, however well-intentioned, are unlikely to accomplish their goals. We need to advocate as physicians and leaders in our settings for every policy, practice, and procedure to be scrutinized using an antiracist lens. To execute this, we need to:

• ask why clinic and hospital practices are built the way they are and how to make them more reflexive and responsive to individual patient’s needs
• examine what the disproportionate impacts might be on different groups of patients from a systems-level
• be ready to dismantle and/or rebuild something that is exacerbating disparate outcomes and experiences
• advocate for change that is built upon the narratives of patients and their communities.

We should include patients in the creation of hospital policies and guidelines in order to shift power toward them and to be transparent about how the system operates in order to facilitate trust and collaboration that centers patients and communities in the systems created to serve them.

Continue to: 4. Intentionally repair and build trust...

4. Intentionally repair and build trust. To create a safe environment, we must repair what we have broken and earn the trust of communities by uplifting their voices and redistributing our power to them in changing the systems and structures that have, for generations, kept Black, Indigenous, and Latinx people oppressed. Building trust requires first owning our histories of colonization, genocide, and slavery—now turned mass incarceration, debasement, and exploitation—that has existed for centuries. We as physicians need to do an honest examination of how we have eroded the trust of the very communities we care for since our profession’s creation. We need to acknowledge, as a white-dominant profession, the medical experimentation on and exploitation of Black and Brown bodies, and how this formed the foundation for a very valid deep distrust and fear of the medical establishment. We need to recognize how our inherent racial biases continue to feed this distrust, like when we don’t treat patients’ pain adequately or make them feel like we believe and listen to their needs and concerns. We must acknowledge our complicity in perpetuating the racial inequities in health, again highlighted by the COVID-19 pandemic.

5. Increase Black, Indigenous, and Latinx representation in physician and other health care professions’ workforce. Racism impacts not only patients but also our colleagues of color. The lack of racial diversity is a symptom of racism and a representation of the continued exclusion and devaluing of physicians of color. We must recognize this legacy of exclusion and facilitate intentional recruitment, retention, inclusion, and belonging of people of color into our workforce. Tokenism, the act of symbolically including one or few people from underrepresented groups, has been a weapon used by our workforce against physicians of color, resulting in isolation, “othering,” demoralization, and other deleterious impacts. We need to reverse this history and diversify our training programs and workforce to ensure justice in our own community.

6. Design multifaceted interventions. Multilevel problems require multilevel solutions. Interventions targeted solely at one level, while helpful, are unlikely to result in the larger scale changes our society needs to implement if we are to eradicate the impact of racism on health. We have long known that it is not just “preexisting conditions” or “poor” individual behaviors that lead to negative and disparate health outcomes—these are impacted by social and structural determinants much larger and more deleterious than that. It is critically important that we allocate and redistribute resources to create safe and affordable housing; childcare and preschool facilities; healthy, available, and affordable food; equitable and affordable educational opportunities; and a clean environment to support the health of all communities—not only those with the highest tax base. It is imperative that we strive to understand the lives of our fellow human beings who have been subjected to intergenerational social injustices and oppressions that have continued to place them at the margins of society. We need to center the lived experiences of communities of color in the design of multilevel interventions, especially Black and Indigenous communities. While we as physicians cannot individually impact education, economic, or food/environment systems, we can use our power to advocate for providing resources for the patients we care for and can create strategies within the health care system to address these needs in order to achieve optimal health. Robust and equitable social structures are the foundations for health, and ensuring equitable access to them is critical to reducing disparities.

Commit to lead

We must commit to unlearning our internalized racism, rebuilding relationships with communities of color, and engaging in antiracist practices. As a profession dedicated to healing, we have an obligation to be leaders in advocating for these changes, and dismantling the inequitable structure of our health care system.

Our challenge now is to articulate solutions. While antiracism should be informed by the lived experiences of communities of color, the work of antiracism is not their responsibility. In fact, it is the responsibility of our white-dominated systems and institutions to change.

There are some solutions that are easier to enumerate because they have easily measurable outcomes or activities, such as:

• collecting data transparently
• identifying inequities in access, treatment, and care
• conducting rigorous root cause analysis of those barriers to care
• increasing diverse racial and gender representation on decision-making bodies, from board rooms to committees, from leadership teams to research participants
• redistribute power by paving the way for underrepresented colleagues to participate in clinical, administrative, educational, executive, and health policy spaces
• mentoring new leaders who come from marginalized communities.

Every patient deserves our expertise and access to high-quality care. We should review our patient panels to ensure we are taking steps personally to be just and eliminate disparities, and we should monitor the results of those efforts.

Continue to: Be open to solutions that may make us “uncomfortable”...

Be open to solutions that may make us “uncomfortable”

There are other solutions, perhaps those that would be more effective on a larger scale, which may be harder to measure using our traditional ways of inquiry or measurement. Solutions that may create discomfort, anger, or fear for those who have held their power or positions for a long time. We need to begin to engage in developing, cultivating, and valuing innovative strategies that produce equally valid knowledge, evidence, and solutions without engaging in a randomized controlled trial. We need to reinvent the way inquiry, investigation, and implementation are done, and utilize novel, justice-informed strategies that include real-world evidence to produce results that are applicable to all (not just those willing to participate in sponsored trials). Only then will we be able to provide equitable health outcomes for all.

We also must accept responsibility for the past and humbly ask communities to work with us as we struggle to eliminate racism and dehumanization of Black lives by calling out our actions or inaction, recognizing the impact of our privileged status, and stepping down or stepping aside to allow others to lead. Sometimes it is as simple as turning off the Zoom camera so others can talk. By redistributing power and focusing this work upon the narratives of marginalized communities, we can improve our system for everyone. We must lead with action within our practices and systems; become advocates within our communities, institutions, and profession; strategize and organize interventions at both structural and individual levels to first recognize and name—then change—the systems; and unlearn behaviors that perpetuate racism.

Inaction is shirking our responsibility among the medical community

Benign inaction and unintentional acquiescence with “the way things are and have always been” abdicates our responsibility as physicians to improve the health of our patients and our communities. The modern Hippocratic Oath reminds us: “I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.” We have a professional and ethical responsibility to ensure health equity, and thus racial equity. As physicians, as healers, as leaders we must address racial inequities at all levels as we commit to improving the health of our nation. We can no longer stand silent in the face of the violence, brutality, and injustices our patients, friends, family, neighbors, communities, and society as a whole live through daily. It is unjust and inhumane to do so.

To be silent is to be complicit. As Gandhi said so long ago, we must “be the change we wish to see in the world.” And as Ijeoma Olua teaches us, “Anti-racism is the commitment to fight racism wherever you find it, including in yourself. And it’s the only way forward.”
 

The destructive toll COVID-19 has caused worldwide is devastating. In the United States, the disproportionate deaths of Black, Indigenous, and Latinx people due to structural racism, amplified by economic adversity, is unacceptable. Meanwhile, the continued murder of Black people by those sworn to protect the public is abhorrent and can no longer be ignored. Black lives matter. These crises have rightly gripped our attention, and should galvanize physicians individually and collectively to use our privileged voices and relative power for justice. We must strive for engaged, passionate, and innovative leadership deliberately aimed toward antiracism and equity.

The COVID-19 pandemic has illuminated the vast inequities in our country. It has highlighted the continued poor outcomes our health and health care systems create for Black, Indigenous, and Latinx communities. It also has demonstrated clearly that we are all connected—one large community, interdependent yet rife with differential power, privilege, and oppression. We must address these racial disparities—not only in the name of justice and good health for all but also because it is a moral and ethical imperative for us as physicians—and SARS-CoV-2 clearly shows us that it is in the best interest of everyone to do so.

First step: A deep dive look at systemic racism

What is first needed is an examination and acknowledgement by medicine and health care at large of the deeply entrenched roots of systemic and institutional racism in our profession and care systems, and their disproportionate and unjust impact on the health and livelihood of communities of color. The COVID-19 pandemic is only a recent example that highlights the perpetuation of a system that harms people of color. Racism, sexism, gender discrimination, economic and social injustice, religious persecution, and violence against women and children are age-old. We have yet to see health care institutions implement system-wide intersectional and antiracist practices to address them. Mandatory implicit bias training, policies for inclusion and diversity, and position statements are necessary first steps; however, they are not a panacea. They are insufficient to create the bold changes we need. The time for words has long passed. It is time to listen, to hear the cries of anguish and outrage, to examine our privileged position, to embrace change and discomfort, and most importantly to act, and to lead in dismantling the structures around us that perpetuate racial inequity.

How can we, as physicians and leaders, join in action and make an impact?

Dr. Camara Jones, past president of the American Public Health Association, describes 3 levels of racism:

• structural or systemic
• individual or personally mediated
• internalized.

Interventions at each level are important if we are to promote equity in health and health care. This framework can help us think about the following strategic initiatives.

Continue to: 1. Commit to becoming an antiracist and engage in independent study...

1. Commit to becoming antiracist and engage in independent study. This is an important first step as it will form the foundations for interventions—one cannot facilitate change without understanding the matter at hand. This step also may be the most personally challenging step forcing all of us to wrestle with discomfort, sadness, fear, guilt, and a host of other emotional responses. Remember that great change has never been born out of comfort, and the discomfort physicians may experience while unlearning racism and learning antiracism pales in comparison to what communities of color experience daily. We must actively work to unlearn the racist and anti-Black culture that is so deeply woven into every aspect of our existence.

Learn the history that was not given to us as kids in school. Read the brilliant literary works of Black, Indigenous, and Latinx artists and scholars on dismantling racism. Expand our vocabulary and knowledge of core concepts in racism, racial justice, and equity. Examine and reflect on our day-to-day practices. Be vocal in our commitment to antiracism—the time has passed for staying silent. If you are white, facilitate conversations about race with your white colleagues; the inherent power of racism relegates it to an issue that can never be on the table, but it is time to dismantle that power. Learn what acts of meaningful and intentional alliances are and when we need to give up power or privilege to a person of color. We also need to recognize that we as physicians, while leaders in many spaces, are not leaders in the powerful racial justice grassroots movements. We should learn from these movements, follow their lead, and use our privilege to uplift racial justice in our settings.

2. Embrace the current complexities with empathy and humility, finding ways to exercise our civic responsibility to the public with compassion. During the COVID-19 pandemic we have seen the devastation that social isolation, job loss, and illness can create. Suddenly those who could never have imagined themselves without food are waiting hours in their cars for food bank donations or are finding empty shelves in stores. Those who were not safe at home were suddenly imprisoned indefinitely in unsafe situations. Those who were comfortable, well-insured, and healthy are facing an invisible health threat, insecurity, fear, anxiety, and loss. Additionally, our civic institutions are failing. Those of us who always took our right to vote for granted are being forced to stand in hours’-long lines to exercise that right; while those who have been systematically disenfranchised are enduring even greater threats to their constitutional right to exercise their political power, disallowing them to speak for their families and communities and to vote for the justice they deserve. This may be an opportunity to stop blaming victims and recognize the toll that structural and systemic contributions to inequity have created over generations.

3. Meaningfully engage with and advocate for patients. In health and health care, we must begin to engage with the communities we serve and truly listen to their needs, desires, and barriers to care, and respond accordingly. Policies that try to address the social determinants of health without that engagement, and without the acknowledgement of the structural issues that cause them, however well-intentioned, are unlikely to accomplish their goals. We need to advocate as physicians and leaders in our settings for every policy, practice, and procedure to be scrutinized using an antiracist lens. To execute this, we need to:

• ask why clinic and hospital practices are built the way they are and how to make them more reflexive and responsive to individual patient’s needs
• examine what the disproportionate impacts might be on different groups of patients from a systems-level
• be ready to dismantle and/or rebuild something that is exacerbating disparate outcomes and experiences
• advocate for change that is built upon the narratives of patients and their communities.

We should include patients in the creation of hospital policies and guidelines in order to shift power toward them and to be transparent about how the system operates in order to facilitate trust and collaboration that centers patients and communities in the systems created to serve them.

Continue to: 4. Intentionally repair and build trust...

4. Intentionally repair and build trust. To create a safe environment, we must repair what we have broken and earn the trust of communities by uplifting their voices and redistributing our power to them in changing the systems and structures that have, for generations, kept Black, Indigenous, and Latinx people oppressed. Building trust requires first owning our histories of colonization, genocide, and slavery—now turned mass incarceration, debasement, and exploitation—that has existed for centuries. We as physicians need to do an honest examination of how we have eroded the trust of the very communities we care for since our profession’s creation. We need to acknowledge, as a white-dominant profession, the medical experimentation on and exploitation of Black and Brown bodies, and how this formed the foundation for a very valid deep distrust and fear of the medical establishment. We need to recognize how our inherent racial biases continue to feed this distrust, like when we don’t treat patients’ pain adequately or make them feel like we believe and listen to their needs and concerns. We must acknowledge our complicity in perpetuating the racial inequities in health, again highlighted by the COVID-19 pandemic.

5. Increase Black, Indigenous, and Latinx representation in physician and other health care professions’ workforce. Racism impacts not only patients but also our colleagues of color. The lack of racial diversity is a symptom of racism and a representation of the continued exclusion and devaluing of physicians of color. We must recognize this legacy of exclusion and facilitate intentional recruitment, retention, inclusion, and belonging of people of color into our workforce. Tokenism, the act of symbolically including one or few people from underrepresented groups, has been a weapon used by our workforce against physicians of color, resulting in isolation, “othering,” demoralization, and other deleterious impacts. We need to reverse this history and diversify our training programs and workforce to ensure justice in our own community.

6. Design multifaceted interventions. Multilevel problems require multilevel solutions. Interventions targeted solely at one level, while helpful, are unlikely to result in the larger scale changes our society needs to implement if we are to eradicate the impact of racism on health. We have long known that it is not just “preexisting conditions” or “poor” individual behaviors that lead to negative and disparate health outcomes—these are impacted by social and structural determinants much larger and more deleterious than that. It is critically important that we allocate and redistribute resources to create safe and affordable housing; childcare and preschool facilities; healthy, available, and affordable food; equitable and affordable educational opportunities; and a clean environment to support the health of all communities—not only those with the highest tax base. It is imperative that we strive to understand the lives of our fellow human beings who have been subjected to intergenerational social injustices and oppressions that have continued to place them at the margins of society. We need to center the lived experiences of communities of color in the design of multilevel interventions, especially Black and Indigenous communities. While we as physicians cannot individually impact education, economic, or food/environment systems, we can use our power to advocate for providing resources for the patients we care for and can create strategies within the health care system to address these needs in order to achieve optimal health. Robust and equitable social structures are the foundations for health, and ensuring equitable access to them is critical to reducing disparities.

Commit to lead

We must commit to unlearning our internalized racism, rebuilding relationships with communities of color, and engaging in antiracist practices. As a profession dedicated to healing, we have an obligation to be leaders in advocating for these changes, and dismantling the inequitable structure of our health care system.

Our challenge now is to articulate solutions. While antiracism should be informed by the lived experiences of communities of color, the work of antiracism is not their responsibility. In fact, it is the responsibility of our white-dominated systems and institutions to change.

There are some solutions that are easier to enumerate because they have easily measurable outcomes or activities, such as:

• collecting data transparently
• identifying inequities in access, treatment, and care
• conducting rigorous root cause analysis of those barriers to care
• increasing diverse racial and gender representation on decision-making bodies, from board rooms to committees, from leadership teams to research participants
• redistribute power by paving the way for underrepresented colleagues to participate in clinical, administrative, educational, executive, and health policy spaces
• mentoring new leaders who come from marginalized communities.

Every patient deserves our expertise and access to high-quality care. We should review our patient panels to ensure we are taking steps personally to be just and eliminate disparities, and we should monitor the results of those efforts.

Continue to: Be open to solutions that may make us “uncomfortable”...

Be open to solutions that may make us “uncomfortable”

There are other solutions, perhaps those that would be more effective on a larger scale, which may be harder to measure using our traditional ways of inquiry or measurement. Solutions that may create discomfort, anger, or fear for those who have held their power or positions for a long time. We need to begin to engage in developing, cultivating, and valuing innovative strategies that produce equally valid knowledge, evidence, and solutions without engaging in a randomized controlled trial. We need to reinvent the way inquiry, investigation, and implementation are done, and utilize novel, justice-informed strategies that include real-world evidence to produce results that are applicable to all (not just those willing to participate in sponsored trials). Only then will we be able to provide equitable health outcomes for all.

We also must accept responsibility for the past and humbly ask communities to work with us as we struggle to eliminate racism and dehumanization of Black lives by calling out our actions or inaction, recognizing the impact of our privileged status, and stepping down or stepping aside to allow others to lead. Sometimes it is as simple as turning off the Zoom camera so others can talk. By redistributing power and focusing this work upon the narratives of marginalized communities, we can improve our system for everyone. We must lead with action within our practices and systems; become advocates within our communities, institutions, and profession; strategize and organize interventions at both structural and individual levels to first recognize and name—then change—the systems; and unlearn behaviors that perpetuate racism.

Inaction is shirking our responsibility among the medical community

Benign inaction and unintentional acquiescence with “the way things are and have always been” abdicates our responsibility as physicians to improve the health of our patients and our communities. The modern Hippocratic Oath reminds us: “I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.” We have a professional and ethical responsibility to ensure health equity, and thus racial equity. As physicians, as healers, as leaders we must address racial inequities at all levels as we commit to improving the health of our nation. We can no longer stand silent in the face of the violence, brutality, and injustices our patients, friends, family, neighbors, communities, and society as a whole live through daily. It is unjust and inhumane to do so.

To be silent is to be complicit. As Gandhi said so long ago, we must “be the change we wish to see in the world.” And as Ijeoma Olua teaches us, “Anti-racism is the commitment to fight racism wherever you find it, including in yourself. And it’s the only way forward.”
 

CASE Patient questions need for postpartum BP check

Ms. P presents at 28 weeks’ gestation with superimposed preeclampsia. She receives antenatal corticosteroids and titration of her nifedipine, but she is delivered at 29 weeks because of worsening fetal status. Her physician recommends a blood pressure (BP) visit in the office at 7 days postpartum.

She asks, “But can’t I just call you with the BP reading? And what do I do in the meantime?”

Hypertensive disorders of pregnancy and chronic hypertension remain among the leading causes of maternal morbidity and mortality in the United States and worldwide.¹ The postpartum period remains a particularly high-risk time since up to 40% of maternal mortality can occur after delivery. To that end, the 2013 American College of Obstetricians and Gynecologists Hypertension in Pregnancy Task Force recommends postpartum follow-up 7 to 10 days after delivery in women with a hypertensive disorder of pregnancy.²

Why we need to find an alternative approach

Unfortunately, these guidelines are both cumbersome and insufficient. Up to one-third of patients do not attend their postpartum visit, particularly those who are young, uninsured, and nonwhite, a list uncomfortably similar to that for women most at risk for adverse outcomes after a high-risk pregnancy. In addition, the 7- to 10-day visit still represents only a single snapshot of the patient’s BP values rather than an ongoing assessment of symptoms or BP elevation over time. Moreover, studies also have shown that BP in both normotensive and hypertensive women often rises by the fifth day postpartum, suggesting that leaving this large window of time without surveillance may miss an opportunity to detect elevated BP in a more timely manner.³

It is time to break the habit of the in-office postpartum BP check and to evaluate the patient where she is and when she needs it. Research in the last 2 years shows that there are several solutions to our case patient’s question.

Solution 1: The provider-driven system

“Of course. Text us your numbers, and you will hear from the doctor if you need to do anything differently.”

One method that addresses both the communication and safety issues inherent in the 7- to 10-day routine in-office BP check is to have the patient send in her BP measurements for direct clinician review.

Researchers at the University of Pennsylvania developed a robust program using their Way to Health platform.⁴ Participating patients text their BP values twice daily, and they receive automated feedback for all values, with additional human feedback in real time from a clinician for severe-range values (>160 mm Hg systolic or >110 mm Hg diastolic). As an added safety measure, a physician reviews all inputted BPs daily and assesses the need for antihypertensive medication for BPs in the high mild range. Using this protocol, the researchers achieved a significant increase in adherence with the recommendation for reporting a BP value in the first 10 days after discharge (from 44% to 92%) as well as having fewer readmissions in the text-messaging arm (4% vs 0%).

Perhaps most impressive, though, is that the technology use eliminated pre-existing racial disparities in adherence. Black participants were as likely as nonblack participants to report a postpartum BP in the text-messaging system (93% vs 91%) despite being less than half as likely to keep a BP check visit (33% vs 70%).⁵

A similar solution is in place at the University of Pittsburgh, where a text message system on the Vivify platform is used to deliver patient BP measurements to a centralized monitoring team.⁶ This program is unique in that, rather than relying on a single physician, it is run through a nurse “call center” that allowed them to expand to 3 hospitals with the use of a single centralized monitoring team. To date, the program has enrolled more than 2,000 patients and achieved patient satisfaction rates greater than 94%.

A final program to consider was developed and piloted at the University of Wisconsin with an added technological advance: the use of a Bluetooth-enabled BP cuff that permits values to be automatically transmitted to a tablet that then uploads the information to a centralized database.⁷ This database was in turn monitored by trained nurses for safety and initiation or titration of antihypertensive medication as needed. Similar to the experience at the University of Pennsylvania, the researchers found improved adherence with monitoring and a notable reduction in readmissions (3.7% in controls vs 0.5% in the intervention arm). Of note, among those who did receive the ongoing monitoring, severe hypertension occurred in 56 (26.2%) of those patients and did so a mean of 6 days after discharge (that is, prior to when they typically would have seen a provider.)

The promise of such provider-driven systems is that they represent a true chronicle of a patient’s ongoing clinical course rather than a single snapshot of her BP in an artificial environment (and often after the highest risk time period!). In addition, direct monitoring by clinicians ensures an optimal safety profile.

Such systems, however, are also extremely resource intense in terms of both upfront information technology investment and ongoing provider surveillance. The systems above also relied on giving the patients a BP cuff, so it is unclear whether it was the technology support or this simple intervention that yielded the benefits. Nonetheless, the benefits were undeniable, and the financial costs saved by reducing even 1 hospital admission as well as the costs of outpatient surveillance may in the end justify these upfront expenditures.

Continue to: Solution 2: The algorithm-driven system...

Solution 2: The algorithm-driven system

“Sure. Plug your numbers into our system, and you’ll receive an automated response as to what to do next.”

One way to alleviate both the financial and opportunity cost of constant clinician surveillance would be to offload some tasks to algorithmic support. This approach—home BP monitoring accompanied by self-titration of antihypertensive medication—has been validated in outpatient primary care hypertension management in nonpregnant adults and more recently for postpartum patients as well.

In the SNAP-HT trial, investigators randomly assigned women to either usual care or algorithm-driven outpatient BP management.⁸ While both groups had serial visits (for safety monitoring), those in the experimental arm were advised only by the algorithm for any ongoing titration of medication. At 6 weeks, the investigators found that BPs were lower in the intervention group, and diastolic BPs remained lower at 6 months.

This methodology emphasizes the potential utility of true self-management of hypertension in the postpartum period. It relies, however, on having a highly developed system in place that can receive the data, respond with recommendations, and safely monitor for any aberrations in the feed. Still, this hybrid method may represent the sweet spot: a combination that ensures adequate surveillance while not overburdening the clinician with the simpler, initial steps in postpartum antihypertensive management.

Solution 3: The DIY system

“That’s a good point. I want to hear about your blood pressure readings in the meantime. Here’s what we can do.”

What about the 99% of practicing ObGyns who do not have an entire connected system for remote hypertension monitoring? A number of options can be put in place today with little cost and even less tech know-how (see “Do-it-yourself options for remote blood pressure monitoring,” below). Note that since many of these options would not be monitored in “real time” like the connected systems discussed above, the patient should be given strict parameters for contacting her clinician directly. These do-it-yourself, or DIY, methods are instead best for the purpose of chronic monitoring and medication titration but are still an improvement in communication over the single-serve BP check.

The bottom line

Pregnant women represent one of the most connected, Internet-savvy demographic groups of any patient population: More than three-quarters of pregnant women turn to the Internet for advice during their pregnancy.^9,10 In addition, unlike most social determinants of health, such as housing, food access, and health care coverage, access to connected electronic devices differs little across racial lines, suggesting the potential for targeting health care inequities by implementing more—not less—technology into prenatal and postpartum care.

For this generation of new mothers, the in-office postpartum BP check is insufficient, artificial, and simply a waste of everyone’s time. While there is no one-size-fits-all approach, there are many options, and it is up to us as health care providers to facilitate the right care, in the right place, at the right time for our patients. ●

Acknowledgements: The authors would like to thank Haritha Pavuluri, Margaret Oliver, and Samantha Boniface for their assistance in the preparation of this manuscript.