OBG Management

PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

PCOS is a common problem, with a prevalence of 6% to 10% among women of reproductive age.¹ Patients with PCOS often present with hirsutism, acne, female androgenetic alopecia, oligomenorrhea (also known as infrequent menstrual bleeding), amenorrhea, infertility, overweight, or obesity. In addition, many patients with PCOS have insulin resistance, dyslipidemia, metabolic syndrome, and an increased risk for developing type 2 diabetes mellitus (DM).² A simplified approach to the diagnosis of PCOS will save health care resources by reducing the use of low-value diagnostic tests. A simplified approach to the treatment of PCOS will support patient medication adherence and improve health outcomes.

Simplify the diagnosis of PCOS

Simplify PCOS diagnosis by focusing on the core criteria of hyperandrogenism and oligo-ovulation. There are 3 major approaches to diagnosis:

1. the 1990 National Institutes of Health (NIH) criteria³
2. the 2003 Rotterdam criteria^4,5
3. the 2008 Androgen Excess and PCOS Society (AES) criteria.⁶

Using the 1990 NIH approach, the diagnosis of PCOS is made by the presence of 2 core criteria: hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea. In addition, other causes of hyperandrogenism should be excluded, including nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency.³ Using the 1990 NIH criteria, PCOS can be diagnosed based on history (oligomenorrhea) and physical examination (assessment of the severity of hirsutism), but laboratory tests including total testosterone are often ordered.⁷

The Rotterdam approach to the diagnosis added a third criteria, the detection by ultrasonography of a multifollicular ovary and/or increased ovarian volume.^4,5 Using the Rotterdam approach, PCOS is diagnosed in the presence of any 2 of the following 3 criteria: hyperandrogenism, oligo-ovulation, or ultrasound imaging showing the presence of a multifollicular ovary, identified by ≥ 12 antral follicles (2 to 9 mm in diameter) in each ovary or increased ovarian volume (> 10 mL).^4,5

The Rotterdam approach using ovarian ultrasound as a criterion to diagnose PCOS is rife with serious problems, including:

• The number of small antral follicles in the normal ovary is age dependent, and many ovulatory and nonhirsute patients have ≥ 12 small antral follicles in each ovary.^8,9
• There is no consensus on the number of small antral follicles needed to diagnose a multifollicular ovary, with recommendations to use thresholds of 12^4,5 or 20 follicles¹⁰ as the diagnostic cut-off.
• Accurate counting of the number of small ovarian follicles requires transvaginal ultrasound, which is not appropriate for many young adolescent patients.
• The process of counting ovarian follicles is operator-dependent.
• The high cost of ultrasound assessment of ovarian follicles (≥ $500 per examination).

The Rotterdam approach supports the diagnosis of PCOS in a patient with oligo-ovulation plus an ultrasound showing a multifollicular ovary in the absence of any clinical or laboratory evidence of hyperandrogenism.^3,4,5 This approach to the diagnosis of PCOS is rejected by both the 1990 NIH³ and AES⁶ recommendations, which require the presence of hyperandrogenism as the sine qua non in the diagnosis of PCOS. I recommend against diagnosing PCOS in a non-hyperandrogenic patient with oligo-ovulation and a multifollicular ovary because other diagnoses are also possible, such as functional hypothalamic oligo-ovulation, especially in young patients. The Rotterdam approach also supports the diagnosis of PCOS in a patient with hyperandrogenism, an ultrasound showing a multifollicular ovary, and normal ovulation and menses.^3,4 For most patients with normal, regular ovulation and menses, the testosterone concentration is normal and the only evidence of hyperandrogenism is hirsutism. Patients with normal, regular ovulation and menses plus hirsutism usually have idiopathic hirsutism. Idiopathic hirsutism is a problem caused by excessive 5-alpha-reductase activity in the hair pilosebaceous unit, which catalyzes the conversion of weak androgens into dihydrotestosterone, a potent intracellular androgen that stimulates terminal hair growth.¹¹ In my opinion, the Rotterdam approach to diagnosing PCOS has created unnecessary confusion and complexity for both clinicians and patients. I believe we should simplify the diagnosis of PCOS and return to the 1990 NIH criteria.³

On occasion, a patient presents for a consultation and has already had an ovarian ultrasound to assess for a multifollicular ovary. I carefully read the report and, if a multifollicular ovary has been identified, I consider it as a secondary supporting finding of PCOS in my clinical assessment. But I do not base my diagnosis on the ultrasound finding. Patients often present with other laboratory tests that are secondary supporting findings of PCOS, which I carefully consider but do not use to make a diagnosis of PCOS. Secondary supporting laboratory findings consistent with PCOS include: 1) a markedly elevated anti-müllerian hormone (AMH) level,¹² 2) an elevated fasting insulin level,^2,13 and 3) an elevated luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio.^13,14 But it is not necessary to measure AMH, fasting insulin, LH, and FSH levels. To conserve health care resources, I recommend against measuring those analytes to diagnose PCOS.

Continue to: Simplify the core laboratory tests...

Simplify the core laboratory tests

Simplify the testing used to support the diagnosis of PCOS by measuring total testosterone, sex-hormone binding globulin (SHBG) and early morning 17-hydroxyprogesterone (17-OH Prog).

The core criteria for diagnosis of PCOS are hyperandrogenism and oligo-ovulation, typically manifested as oligomenorrhea or amenorrhea. Hyperandrogenism can be clinically diagnosed by assessing for the presence of hirsutism.⁷ Elevated levels of total testosterone, free testosterone, androstenedione, and/or dehydroepiandrosterone sulfate (DHEAS) suggest the presence of hyperandrogenism. In clinical practice, the laboratory approach to the diagnosis of hyperandrogenism can be simplified to the measurement of total testosterone, SHBG, and 17-OH Prog. By measuring total testosterone and SHBG, an estimate of free testosterone can be made. If the total testosterone is elevated, it is highly likely that the free testosterone is elevated. If the SHBG is abnormally low and the total testosterone level is in the upper limit of the normal range, the free testosterone is likely to be elevated.¹⁵ Using this approach, either an elevated total testosterone or an abnormally low SHBG indicate elevated free testosterone. For patients with hyperandrogenism and oligo-ovulation, an early morning (8 to 9 AM) 17-OH Prog level ≤ 2 ng/mL rules out the presence of NCAH due to a 21-hydroxylase deficiency.¹⁶ In my practice, the core laboratory tests I order when considering the diagnosis of PCOS are a total testosterone, SHBG, and 17-OH Prog.

Additional laboratory tests may be warranted to assess the patient diagnosed with PCOS. For example, if the patient has amenorrhea due to anovulation, tests for prolactin, FSH, and thyroid-stimulating hormone levels are warranted to assess for the presence of a prolactinoma, primary ovarian insufficiency, or thyroid disease, respectively. If the patient has a body mass index (BMI) ≥ 25 kg/m², a hemoglobin A1c concentration is warranted to assess for the presence of prediabetes or DM.² Many patients with PCOS have dyslipidemia, manifested through low high-density lipoprotein cholesterol levels and elevated low-density lipoprotein cholesterol levels, and a lipid panel assessment may be indicated. Among patients with PCOS, the most common lipid abnormality is a low high-density lipoprotein cholesterol level.¹⁷

Simplify the treatment of PCOS

Simplify treatment by counseling about lifestyle changes and prescribing an estrogen-progestin contraceptive, spironolactone, and metformin.

Most patients with PCOS have dysfunction in reproductive, metabolic, and dermatologic systems. For patients who are overweight or obese, lifestyle changes, including diet and exercise, that result in a 5% to 10% decrease in weight can improve metabolic balance, reduce circulating androgens, and increase menstrual frequency.¹⁸ For patients with PCOS and weight issues, referral to nutrition counseling or a full-service weight loss program can be very beneficial. In addition to lifestyle changes, patients with PCOS benefit from treatment with estrogen-progestin medications, spironolactone, and metformin.

Combination estrogen-progestin medications will lower LH secretion, decrease ovarian androgen production, increase SHBG production, decrease free testosterone levels and, if given cyclically, cause regular withdrawal bleeding.¹⁹ Spironolactone is an antiandrogen, which blocks the intracellular action of dihydrotestosterone and improves hirsutism and acne. Spironolactone also modestly decreases circulating levels of testosterone and DHEAS.²⁰ For patients with metabolic problems, including insulin resistance and obesity, weight loss and/or treatment with metformin can help improve metabolic balance, which may result in restoration of ovulatory menses.^21,22 Metformin can be effective in restoring ovulatory menses in both obese and lean patients with PCOS.²² The most common dermatologic problem caused by PCOS are hirsutism and acne. Both combination estrogen-progestin medications and spironolactone are effective treatments for hirsutism and acne.²³

Estrogen-progestin hormones, spironolactone, and metformin are low-cost medications for the treatment of PCOS. Additional high-cost options for treatment of PCOS in obese patients include bariatric surgery and glucagon-like peptide (GLP-1) agonist medications (liraglutide and exenatide). For patients with PCOS and a body mass index (BMI) ≥ 35 kg/m², bariatric surgery often results in sufficient weight loss to resolve the patient’s hyperandrogenism and oligo-ovulation, restoring spontaneous ovulatory cycles.²⁴ In a study of more than 1,000 patients with: PCOS; mean BMI, 44 kg/m²; mean age, 31 years who were followed post-bariatric surgery for 5 years, > 90% of patients reported reductions in hirsutism and resumption of regular menses.²⁵ For patients with PCOS seeking fertility, bariatric surgery often results in spontaneous pregnancy and live birth.²⁶ GLP-1 agonists, including liraglutide or exenatide with or without metformin are effective in reducing weight, decreasing androgen levels, and restoring ovulatory menses.^27,28

In my practice, I often prescribe 2 or 3 core medications for a patient with PCOS: 1) combination estrogen-progestin used cyclically or continuously, 2) spironolactone, and 3) metformin.¹⁹ Any estrogen-progestin contraceptive will suppress LH and ovarian androgen production; however, in the treatment of patients with PCOS, I prefer to use an estrogen-progestin combination that does not contain the androgenic progestin levonorgestrel.²⁹ For the treatment of PCOS, I prefer to use an estrogen-progestin contraceptive with a non-androgenic progestin such as drospirenone, desogestrel, or gestodene. I routinely prescribe spironolactone at a dose of 100 mg, once daily, a dose near the top of the dose-response curve. A daily dose ≤ 50 mg of spironolactone is subtherapeutic for the treatment of hirsutism. A daily dose of 200 mg of spironolactone may cause bothersome breakthrough bleeding. When prescribing metformin, I usually recommend the extended-release formulation, at a dose of 750 mg with dinner. If well tolerated, I will increase the dose to 1,500 mg with dinner. Most of my patients with PCOS are taking a combination of 2 medications, either an estrogen-progestin contraceptive plus spironolactone or an estrogen-progestin contraceptive plus metformin.¹⁹ Some of my patients are taking all 3 medications. All 3 medications are very low cost.

For patients with PCOS and anovulatory infertility, letrozole treatment often results in ovulatory cycles and pregnancy with live birth. In obese PCOS patients, compared with clomiphene, letrozole results in superior live birth rates.³⁰ Unlike clomiphene, letrozole is not approved by the US Food and Drug Administration for the treatment of anovulatory infertility.

The diagnosis of PCOS is often delayed due to confusion about how to make the diagnosis.³¹ To simplify the diagnosis of PCOS and improve patient encounters for PCOS, I focus on 2 core criteria: hyperandrogenism and oligo-ovulation. I recommend against ordering ultrasound imaging to assess for the presence of a multifollicular ovary. To simplify the treatment of PCOS I frequently prescribe an estrogen-progestin contraceptive, spironolactone, and metformin. By simplifying the diagnosis and treatment of PCOS, ObGyns will reduce patient confusion, improve outcomes, and save health care resources. ●

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

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BD ONCLARITY^TM HPV ASSAY

FOR MORE INFORMATION, VISIT: https://womens-health-solutions.bd.com/

BD ONCLARITY^TM HPV ASSAY

FOR MORE INFORMATION, VISIT: https://womens-health-solutions.bd.com/

CASE Concern for surgical management after repeat miscarriage

A 34-year-old woman (G3P0030) with a history of recurrent pregnancy loss was recently diagnosed with a 7-week missed abortion. After her second miscarriage, she had an evaluation for recurrent pregnancy loss which was unremarkable. Both prior miscarriages were managed with dilation & curettage (D&C), but cytogenetic testing of the tissue did not yield a result in either case. The karyotype from the first pregnancy resulted as 46, XX but was confirmed to be due to maternal cell contamination, and the karyotype from the second pregnancy resulted in cell culture failure. The patient is interested in surgical management for her current missed abortion to help with tissue collection for cytogenetic testing, she but is concerned about her risk of intrauterine adhesions with repeated uterine instrumentation given 2 prior D&Cs, one of which was complicated by retained products of conception.

How do you approach the surgical management of this patient with recurrent pregnancy loss?

Approximately 1 in every 8 recognized pregnancies results in miscarriage. The risk of loss is lowest in women with no history of miscarriage (11%), and increases by about 10% for each additional miscarriage, reaching 42% in women with 3 or more previous losses. The population prevalence of women who have had 1 miscarriage is 11%, 2 miscarriages is 2%, and 3 or more is <1%.¹ While 90% of miscarriages occur in the first trimester, their etiology can be quite varied.² A woman’s age is the most strongly associated risk factor, with both very young (<20 years) and older age (>35 years) groups at highest risk. This association is largely attributed to an age-related increase in embryonic chromosomal aneuploidies, of which trisomies, particularly trisomy 16, are the most common.³ Maternal anatomic anomalies such as leiomyomas, intrauterine adhesions, Müllerian anomalies, and adenomyosis have been linked to an increased risk of miscarriage in addition to several lifestyle and environmental factor exposures.¹

Regardless of the etiology, women with recurrent miscarriage are exposed to the potential for iatrogenic harm from the management of their pregnancy loss, including intrauterine adhesions and retained products, which may negatively impact future reproductive attempts. The management of patients with recurrent miscarriages demands special attention to reduce the risk of iatrogenic harm, maximize diagnostic evaluation of the products of conception, and improve future reproductive outcomes.

Management strategies

First trimester pregnancy loss may be managed expectantly, medically, or surgically. Approximately 76% of women who opt for expectant management will successfully pass pregnancy tissue, but for 1 out of every 6 women it may take longer than 14 days.⁴ For patients who prefer to expedite this process, medication abortion is a highly effective and safe option. According to Schreiber and colleagues, a combination of mifepristone and misoprostol together resulted in expulsion in approximately 91% of 148 patients, although 9% still required surgical intervention for incomplete passage of tissue.⁵ Both expectant management and medical management strategies are associated with the potential for retained products of conception requiring subsequent instrumentation as well as tissue that is often unsuitable or contaminated for cytogenetic analysis.

The most definitive treatment option is surgical management via manual or electric vacuum aspiration or curettage, with efficacy approaching 99.6% in some series.⁶ While highly effective, even ultrasound-guided evacuation carries with it procedure-related risks that are of particular consequence for patients of reproductive age, including adhesion formation and retained products of conception.

In 1997, Goldenberg and colleagues reported on the use of hysteroscopy for the management of retained products of conception as a strategy to minimize trauma to the uterus and maximize excision of retained tissue, both of which reduce potential for adhesion formation.⁷ Based on these data, several groups have extended the use of hysteroscopic resection for retained tissue to upfront evacuation following pregnancy loss, in lieu of D&C.^8,9 This approach allows for the direct visualization of the focal removal of the implanted pregnancy tissue, which can:

• decrease the risk of intrauterine adhesion formation
• decrease the risk of retained products of conception
• allow for directed tissue sampling to improve the accuracy of cytogenetic testing
• allow for detection of embryo anatomic anomalies that often go undetected on traditional cytogenetic analysis.

For the remainder of this article, we will discuss the advantages of hysteroscopic management of a missed abortion in greater detail.

Continue to: Hysteroscopic management...

Hysteroscopic management

Like aspiration or curettage, hysteroscopic management may be offered once the diagnosis of fetal demise is confirmed on ultrasonography. The procedure may be accomplished in the office setting or in the operative room with either morcellation or resectoscopic instruments. Morcellation allows for improved visibility during the procedure given the ability of continuous suction to manage tissue fragments in the surgical field, while resectoscopic instruments offer the added benefit of electrosurgery should bleeding that is unresponsive to increased distention pressure be encountered. Use of the cold loop of the resectoscope to accomplish evacuation is advocated to avoid the thermal damage to the endometrium with electrosurgery. Regardless of the chosen instrument, there are several potential benefits for a hysteroscopic approach over the traditional ultrasound-guided or blind D&C.

Reducing risk of iatrogenic harm

Intrauterine adhesions form secondary to trauma to the endometrial basalis layer, where a population of adult progenitor stem cells continuously work to regenerate the overlying functionalis layer. Once damaged, adhesions may form and range from thin, filmy adhesions to dense, cavity obliterating bands of scar tissue (FIGURE). The degree of severity and location of the adhesions account for the variable presentation that range from menstrual abnormalities to infertility and recurrent pregnancy loss. While several classification systems exist for scoring severity of adhesions, the American Fertility Society (now American Society for Reproductive Medicine) Classification system from 1988 is still commonly utilized (TABLE 1).

ILLUSTRATIONS: MARCIA HARTSOCK FOR OBG MANAGEMENT

Intrauterine adhesions from D&C after pregnancy loss are not uncommon. A 2014 meta-analysis of 10 prospective studies including 912 women reported a pooled prevalence for intrauterine adhesions of 19.1% (95% confidence interval [CI], 12.8–27.5) on hysteroscopic evaluation within 12 months following curettage.¹⁰ Once formed, these adhesions are associated with long-term impairment in reproductive outcomes, regardless of if they were treated or not. In a long-term follow-up study of women with and without adhesions after recurrent D&C for miscarriage, women with treated adhesions reported lower live birth rates, longer time to pregnancy, higher rates of preterm birth and higher rates of peripartum complications compared with those without adhesions.¹¹

Compared with curettage, hysteroscopy affords the surgeon complete visualization of the uterine cavity and tissue to be resected. This, in turn, minimizes trauma to the surrounding uterine cavity, minimizes the potential for post-procedural adhesion formation and their associated sequelae, and maximizes complete resection of tissue. Those treated with D&C appear to be significantly more likely to have adhesions than those treated via a hysteroscopic approach (30% vs 13%).¹²

Retained products of conception. Classically, a “gritty” sensation of the endometrium following evacuation of the uterus with a sharp curette has been used to indicate complete removal of tissue. The evolution from a nonvisualized procedure to ultrasound-guided vacuum aspiration of 1st trimester pregnancy tissue has been associated with a decreased risk of procedural complications and retained products of conception.¹³ However, even with intraoperative imaging, the risk of retained products of conception remains because it can be difficult to distinguish a small blood clot from retained pregnancy tissue on ultrasonography.

Retained pregnancy tissue can result in abnormal or heavy bleeding, require additional medical or surgical intervention, and is associated with endometrial inflammation and infection. Approximately 1 in every 4 women undergoing hysteroscopic resection of retained products are found to have evidence of endometritis in the resected tissue.¹⁴ This number is even higher in women with a diagnosis of recurrent pregnancy loss (62%).¹⁵

These complications from retained products of conception can be avoided with the hysteroscopic approach due to the direct visualization of the tissue removal. This benefit may be particularly beneficial in patients with known abnormal uterine cavities, such as those with Müllerian anomalies, uterine leiomyomas, preexisting adhesions, and history of placenta accreta spectrum disorder.

Continue to: Maximizing diagnostic yield...

Maximizing diagnostic yield

Many patients prefer surgical management of a missed abortion not for the procedural advantages, but to assist with tissue collection for cytogenetic testing of the pregnancy tissue. Given that embryonic chromosomal aneuploidy is implicated in 70% of miscarriages prior to 20 weeks’ gestation, genetic evaluation of the products of conception is commonly performed to identify a potential cause for the miscarriage.¹⁶ G-band karyotype is the most commonly performed genetic evaluation. Karyotype requires culturing of pregnancy tissue for 7-14 days to produce metaphase cells that are then chemically treated to arrest them at their maximally contracted stage. Cytogenetic evaluation is often curtailed when nonviable cells from products of conception fail to culture due to either time elapsed from diagnosis to demise or damage from tissue handling. Careful, directly observed tissue handling via a hysteroscopic approach may alleviate culture failure secondary to tissue damage.

Another concern with cultures of products of conception is the potential for maternal cell contamination. Early studies from the 1970s noted a significant skew toward 46, XX karyotype results in miscarried tissue as compared with 46, XY results. It was not until microsatellite analysis technology was available that it was determined that the result was due to analysis of maternal cells instead of products of conception.¹⁷ A 2014 study by Levy and colleagues and another by Lathi and colleagues that utilized single-nucleotide polymorphism (SNP) microarray found that maternal cell contamination affected 22% of all miscarriage samples analyzed and over half of karyotypes with a 46, XX result.^18,19

Traditional “blind” suction and curettage may inadvertently collect maternal endometrial tissue and contaminate the culture of fetal cells, limiting the validity of karyotype for products of conception.²⁰ The hysteroscopic approach may provide a higher diagnostic yield for karyotype analysis of fetal tissue by the nature of targeted tissue sampling under direct visualization, minimizing maternal cell contamination. One retrospective study by Cholkeri-Singh and colleagues evaluated rates of fetal chromosome detection without maternal contamination in a total of 264 patients undergoing either suction curettage or hysteroscopic resection. They found that fetal chromosomal detection without contamination was significantly higher in the hysteroscopy group compared with the suction curettage group (88.5 vs 64.8%, P< .001).²¹ Additionally, biopsies of tissue under direct visualization may enable the diagnosis of a true placental mosaicism and the study of the individual karyotype of each embryo in dizygotic twin missed abortions.

Finally, a hysteroscopic approach may afford the opportunity to also perform morphologic evaluation of the intact early fetus furthering the diagnostic utility of the procedure. With hysteroscopy, the gestational sac is identified and carefully entered, allowing for complete visualization of the early fetus and assessment of anatomic malformations that may provide insight into the pregnancy loss (ie, embryoscopy). In one series of 272 patients with missed abortions, while nearly 75% of conceptuses had abnormal karyotypes, 18% were found to have gross morphologic defects with a normal karyotype.²²

Bottom line

When faced with a patient with an early pregnancy loss, physicians should consider the decreased iatrogenic risks and improved diagnostic yield when deciding between D&C versus hysteroscopy for surgical management. There are certain patients with pre-existing risk factors that may stand to benefit the most (TABLE 2). Much like the opening case, those at risk for intrauterine adhesions, retained products of conception, or in whom a successful and accurate cytogenetic analysis is essential are the most likely to benefit from a hysteroscopic approach. The hysteroscopic approach also affords concurrent diagnosis and treatment of intrauterine pathology, such as leiomyomas and uterine septum, which are encountered approximately 12.5% of the time after one miscarriage and 29.4% of the time in patients with a history of more than one miscarriage.¹⁰ In the appropriately counseled patient and clinical setting, clinicians could also perform definitive surgical management during the same hysteroscopy. Finally, evaluation of the morphology of the demised fetus may provide additional information for patient counseling in those with euploid pregnancy losses.

CASE Resolved

Ultimately, our patient underwent complete hysteroscopic resection of the pregnancy tissue, which confirmed both a morphologically abnormal fetus and a 45, X karyotype of the products of conception. ●

CASE Concern for surgical management after repeat miscarriage

A 34-year-old woman (G3P0030) with a history of recurrent pregnancy loss was recently diagnosed with a 7-week missed abortion. After her second miscarriage, she had an evaluation for recurrent pregnancy loss which was unremarkable. Both prior miscarriages were managed with dilation & curettage (D&C), but cytogenetic testing of the tissue did not yield a result in either case. The karyotype from the first pregnancy resulted as 46, XX but was confirmed to be due to maternal cell contamination, and the karyotype from the second pregnancy resulted in cell culture failure. The patient is interested in surgical management for her current missed abortion to help with tissue collection for cytogenetic testing, she but is concerned about her risk of intrauterine adhesions with repeated uterine instrumentation given 2 prior D&Cs, one of which was complicated by retained products of conception.

How do you approach the surgical management of this patient with recurrent pregnancy loss?

Approximately 1 in every 8 recognized pregnancies results in miscarriage. The risk of loss is lowest in women with no history of miscarriage (11%), and increases by about 10% for each additional miscarriage, reaching 42% in women with 3 or more previous losses. The population prevalence of women who have had 1 miscarriage is 11%, 2 miscarriages is 2%, and 3 or more is <1%.¹ While 90% of miscarriages occur in the first trimester, their etiology can be quite varied.² A woman’s age is the most strongly associated risk factor, with both very young (<20 years) and older age (>35 years) groups at highest risk. This association is largely attributed to an age-related increase in embryonic chromosomal aneuploidies, of which trisomies, particularly trisomy 16, are the most common.³ Maternal anatomic anomalies such as leiomyomas, intrauterine adhesions, Müllerian anomalies, and adenomyosis have been linked to an increased risk of miscarriage in addition to several lifestyle and environmental factor exposures.¹

Regardless of the etiology, women with recurrent miscarriage are exposed to the potential for iatrogenic harm from the management of their pregnancy loss, including intrauterine adhesions and retained products, which may negatively impact future reproductive attempts. The management of patients with recurrent miscarriages demands special attention to reduce the risk of iatrogenic harm, maximize diagnostic evaluation of the products of conception, and improve future reproductive outcomes.

Management strategies

First trimester pregnancy loss may be managed expectantly, medically, or surgically. Approximately 76% of women who opt for expectant management will successfully pass pregnancy tissue, but for 1 out of every 6 women it may take longer than 14 days.⁴ For patients who prefer to expedite this process, medication abortion is a highly effective and safe option. According to Schreiber and colleagues, a combination of mifepristone and misoprostol together resulted in expulsion in approximately 91% of 148 patients, although 9% still required surgical intervention for incomplete passage of tissue.⁵ Both expectant management and medical management strategies are associated with the potential for retained products of conception requiring subsequent instrumentation as well as tissue that is often unsuitable or contaminated for cytogenetic analysis.

The most definitive treatment option is surgical management via manual or electric vacuum aspiration or curettage, with efficacy approaching 99.6% in some series.⁶ While highly effective, even ultrasound-guided evacuation carries with it procedure-related risks that are of particular consequence for patients of reproductive age, including adhesion formation and retained products of conception.

In 1997, Goldenberg and colleagues reported on the use of hysteroscopy for the management of retained products of conception as a strategy to minimize trauma to the uterus and maximize excision of retained tissue, both of which reduce potential for adhesion formation.⁷ Based on these data, several groups have extended the use of hysteroscopic resection for retained tissue to upfront evacuation following pregnancy loss, in lieu of D&C.^8,9 This approach allows for the direct visualization of the focal removal of the implanted pregnancy tissue, which can:

• decrease the risk of intrauterine adhesion formation
• decrease the risk of retained products of conception
• allow for directed tissue sampling to improve the accuracy of cytogenetic testing
• allow for detection of embryo anatomic anomalies that often go undetected on traditional cytogenetic analysis.

For the remainder of this article, we will discuss the advantages of hysteroscopic management of a missed abortion in greater detail.

Continue to: Hysteroscopic management...

Hysteroscopic management

Like aspiration or curettage, hysteroscopic management may be offered once the diagnosis of fetal demise is confirmed on ultrasonography. The procedure may be accomplished in the office setting or in the operative room with either morcellation or resectoscopic instruments. Morcellation allows for improved visibility during the procedure given the ability of continuous suction to manage tissue fragments in the surgical field, while resectoscopic instruments offer the added benefit of electrosurgery should bleeding that is unresponsive to increased distention pressure be encountered. Use of the cold loop of the resectoscope to accomplish evacuation is advocated to avoid the thermal damage to the endometrium with electrosurgery. Regardless of the chosen instrument, there are several potential benefits for a hysteroscopic approach over the traditional ultrasound-guided or blind D&C.

Reducing risk of iatrogenic harm

Intrauterine adhesions form secondary to trauma to the endometrial basalis layer, where a population of adult progenitor stem cells continuously work to regenerate the overlying functionalis layer. Once damaged, adhesions may form and range from thin, filmy adhesions to dense, cavity obliterating bands of scar tissue (FIGURE). The degree of severity and location of the adhesions account for the variable presentation that range from menstrual abnormalities to infertility and recurrent pregnancy loss. While several classification systems exist for scoring severity of adhesions, the American Fertility Society (now American Society for Reproductive Medicine) Classification system from 1988 is still commonly utilized (TABLE 1).

ILLUSTRATIONS: MARCIA HARTSOCK FOR OBG MANAGEMENT

Intrauterine adhesions from D&C after pregnancy loss are not uncommon. A 2014 meta-analysis of 10 prospective studies including 912 women reported a pooled prevalence for intrauterine adhesions of 19.1% (95% confidence interval [CI], 12.8–27.5) on hysteroscopic evaluation within 12 months following curettage.¹⁰ Once formed, these adhesions are associated with long-term impairment in reproductive outcomes, regardless of if they were treated or not. In a long-term follow-up study of women with and without adhesions after recurrent D&C for miscarriage, women with treated adhesions reported lower live birth rates, longer time to pregnancy, higher rates of preterm birth and higher rates of peripartum complications compared with those without adhesions.¹¹

Compared with curettage, hysteroscopy affords the surgeon complete visualization of the uterine cavity and tissue to be resected. This, in turn, minimizes trauma to the surrounding uterine cavity, minimizes the potential for post-procedural adhesion formation and their associated sequelae, and maximizes complete resection of tissue. Those treated with D&C appear to be significantly more likely to have adhesions than those treated via a hysteroscopic approach (30% vs 13%).¹²

Retained products of conception. Classically, a “gritty” sensation of the endometrium following evacuation of the uterus with a sharp curette has been used to indicate complete removal of tissue. The evolution from a nonvisualized procedure to ultrasound-guided vacuum aspiration of 1st trimester pregnancy tissue has been associated with a decreased risk of procedural complications and retained products of conception.¹³ However, even with intraoperative imaging, the risk of retained products of conception remains because it can be difficult to distinguish a small blood clot from retained pregnancy tissue on ultrasonography.

Retained pregnancy tissue can result in abnormal or heavy bleeding, require additional medical or surgical intervention, and is associated with endometrial inflammation and infection. Approximately 1 in every 4 women undergoing hysteroscopic resection of retained products are found to have evidence of endometritis in the resected tissue.¹⁴ This number is even higher in women with a diagnosis of recurrent pregnancy loss (62%).¹⁵

These complications from retained products of conception can be avoided with the hysteroscopic approach due to the direct visualization of the tissue removal. This benefit may be particularly beneficial in patients with known abnormal uterine cavities, such as those with Müllerian anomalies, uterine leiomyomas, preexisting adhesions, and history of placenta accreta spectrum disorder.

Continue to: Maximizing diagnostic yield...

Maximizing diagnostic yield

Many patients prefer surgical management of a missed abortion not for the procedural advantages, but to assist with tissue collection for cytogenetic testing of the pregnancy tissue. Given that embryonic chromosomal aneuploidy is implicated in 70% of miscarriages prior to 20 weeks’ gestation, genetic evaluation of the products of conception is commonly performed to identify a potential cause for the miscarriage.¹⁶ G-band karyotype is the most commonly performed genetic evaluation. Karyotype requires culturing of pregnancy tissue for 7-14 days to produce metaphase cells that are then chemically treated to arrest them at their maximally contracted stage. Cytogenetic evaluation is often curtailed when nonviable cells from products of conception fail to culture due to either time elapsed from diagnosis to demise or damage from tissue handling. Careful, directly observed tissue handling via a hysteroscopic approach may alleviate culture failure secondary to tissue damage.

Another concern with cultures of products of conception is the potential for maternal cell contamination. Early studies from the 1970s noted a significant skew toward 46, XX karyotype results in miscarried tissue as compared with 46, XY results. It was not until microsatellite analysis technology was available that it was determined that the result was due to analysis of maternal cells instead of products of conception.¹⁷ A 2014 study by Levy and colleagues and another by Lathi and colleagues that utilized single-nucleotide polymorphism (SNP) microarray found that maternal cell contamination affected 22% of all miscarriage samples analyzed and over half of karyotypes with a 46, XX result.^18,19

Traditional “blind” suction and curettage may inadvertently collect maternal endometrial tissue and contaminate the culture of fetal cells, limiting the validity of karyotype for products of conception.²⁰ The hysteroscopic approach may provide a higher diagnostic yield for karyotype analysis of fetal tissue by the nature of targeted tissue sampling under direct visualization, minimizing maternal cell contamination. One retrospective study by Cholkeri-Singh and colleagues evaluated rates of fetal chromosome detection without maternal contamination in a total of 264 patients undergoing either suction curettage or hysteroscopic resection. They found that fetal chromosomal detection without contamination was significantly higher in the hysteroscopy group compared with the suction curettage group (88.5 vs 64.8%, P< .001).²¹ Additionally, biopsies of tissue under direct visualization may enable the diagnosis of a true placental mosaicism and the study of the individual karyotype of each embryo in dizygotic twin missed abortions.

Finally, a hysteroscopic approach may afford the opportunity to also perform morphologic evaluation of the intact early fetus furthering the diagnostic utility of the procedure. With hysteroscopy, the gestational sac is identified and carefully entered, allowing for complete visualization of the early fetus and assessment of anatomic malformations that may provide insight into the pregnancy loss (ie, embryoscopy). In one series of 272 patients with missed abortions, while nearly 75% of conceptuses had abnormal karyotypes, 18% were found to have gross morphologic defects with a normal karyotype.²²

Bottom line

When faced with a patient with an early pregnancy loss, physicians should consider the decreased iatrogenic risks and improved diagnostic yield when deciding between D&C versus hysteroscopy for surgical management. There are certain patients with pre-existing risk factors that may stand to benefit the most (TABLE 2). Much like the opening case, those at risk for intrauterine adhesions, retained products of conception, or in whom a successful and accurate cytogenetic analysis is essential are the most likely to benefit from a hysteroscopic approach. The hysteroscopic approach also affords concurrent diagnosis and treatment of intrauterine pathology, such as leiomyomas and uterine septum, which are encountered approximately 12.5% of the time after one miscarriage and 29.4% of the time in patients with a history of more than one miscarriage.¹⁰ In the appropriately counseled patient and clinical setting, clinicians could also perform definitive surgical management during the same hysteroscopy. Finally, evaluation of the morphology of the demised fetus may provide additional information for patient counseling in those with euploid pregnancy losses.

CASE Resolved

Ultimately, our patient underwent complete hysteroscopic resection of the pregnancy tissue, which confirmed both a morphologically abnormal fetus and a 45, X karyotype of the products of conception. ●

CASE Concern for surgical management after repeat miscarriage

A 34-year-old woman (G3P0030) with a history of recurrent pregnancy loss was recently diagnosed with a 7-week missed abortion. After her second miscarriage, she had an evaluation for recurrent pregnancy loss which was unremarkable. Both prior miscarriages were managed with dilation & curettage (D&C), but cytogenetic testing of the tissue did not yield a result in either case. The karyotype from the first pregnancy resulted as 46, XX but was confirmed to be due to maternal cell contamination, and the karyotype from the second pregnancy resulted in cell culture failure. The patient is interested in surgical management for her current missed abortion to help with tissue collection for cytogenetic testing, she but is concerned about her risk of intrauterine adhesions with repeated uterine instrumentation given 2 prior D&Cs, one of which was complicated by retained products of conception.

How do you approach the surgical management of this patient with recurrent pregnancy loss?

Approximately 1 in every 8 recognized pregnancies results in miscarriage. The risk of loss is lowest in women with no history of miscarriage (11%), and increases by about 10% for each additional miscarriage, reaching 42% in women with 3 or more previous losses. The population prevalence of women who have had 1 miscarriage is 11%, 2 miscarriages is 2%, and 3 or more is <1%.¹ While 90% of miscarriages occur in the first trimester, their etiology can be quite varied.² A woman’s age is the most strongly associated risk factor, with both very young (<20 years) and older age (>35 years) groups at highest risk. This association is largely attributed to an age-related increase in embryonic chromosomal aneuploidies, of which trisomies, particularly trisomy 16, are the most common.³ Maternal anatomic anomalies such as leiomyomas, intrauterine adhesions, Müllerian anomalies, and adenomyosis have been linked to an increased risk of miscarriage in addition to several lifestyle and environmental factor exposures.¹

Regardless of the etiology, women with recurrent miscarriage are exposed to the potential for iatrogenic harm from the management of their pregnancy loss, including intrauterine adhesions and retained products, which may negatively impact future reproductive attempts. The management of patients with recurrent miscarriages demands special attention to reduce the risk of iatrogenic harm, maximize diagnostic evaluation of the products of conception, and improve future reproductive outcomes.

Management strategies

First trimester pregnancy loss may be managed expectantly, medically, or surgically. Approximately 76% of women who opt for expectant management will successfully pass pregnancy tissue, but for 1 out of every 6 women it may take longer than 14 days.⁴ For patients who prefer to expedite this process, medication abortion is a highly effective and safe option. According to Schreiber and colleagues, a combination of mifepristone and misoprostol together resulted in expulsion in approximately 91% of 148 patients, although 9% still required surgical intervention for incomplete passage of tissue.⁵ Both expectant management and medical management strategies are associated with the potential for retained products of conception requiring subsequent instrumentation as well as tissue that is often unsuitable or contaminated for cytogenetic analysis.

The most definitive treatment option is surgical management via manual or electric vacuum aspiration or curettage, with efficacy approaching 99.6% in some series.⁶ While highly effective, even ultrasound-guided evacuation carries with it procedure-related risks that are of particular consequence for patients of reproductive age, including adhesion formation and retained products of conception.

In 1997, Goldenberg and colleagues reported on the use of hysteroscopy for the management of retained products of conception as a strategy to minimize trauma to the uterus and maximize excision of retained tissue, both of which reduce potential for adhesion formation.⁷ Based on these data, several groups have extended the use of hysteroscopic resection for retained tissue to upfront evacuation following pregnancy loss, in lieu of D&C.^8,9 This approach allows for the direct visualization of the focal removal of the implanted pregnancy tissue, which can:

• decrease the risk of intrauterine adhesion formation
• decrease the risk of retained products of conception
• allow for directed tissue sampling to improve the accuracy of cytogenetic testing
• allow for detection of embryo anatomic anomalies that often go undetected on traditional cytogenetic analysis.

For the remainder of this article, we will discuss the advantages of hysteroscopic management of a missed abortion in greater detail.

Continue to: Hysteroscopic management...

Hysteroscopic management

Like aspiration or curettage, hysteroscopic management may be offered once the diagnosis of fetal demise is confirmed on ultrasonography. The procedure may be accomplished in the office setting or in the operative room with either morcellation or resectoscopic instruments. Morcellation allows for improved visibility during the procedure given the ability of continuous suction to manage tissue fragments in the surgical field, while resectoscopic instruments offer the added benefit of electrosurgery should bleeding that is unresponsive to increased distention pressure be encountered. Use of the cold loop of the resectoscope to accomplish evacuation is advocated to avoid the thermal damage to the endometrium with electrosurgery. Regardless of the chosen instrument, there are several potential benefits for a hysteroscopic approach over the traditional ultrasound-guided or blind D&C.

Reducing risk of iatrogenic harm

Intrauterine adhesions form secondary to trauma to the endometrial basalis layer, where a population of adult progenitor stem cells continuously work to regenerate the overlying functionalis layer. Once damaged, adhesions may form and range from thin, filmy adhesions to dense, cavity obliterating bands of scar tissue (FIGURE). The degree of severity and location of the adhesions account for the variable presentation that range from menstrual abnormalities to infertility and recurrent pregnancy loss. While several classification systems exist for scoring severity of adhesions, the American Fertility Society (now American Society for Reproductive Medicine) Classification system from 1988 is still commonly utilized (TABLE 1).

ILLUSTRATIONS: MARCIA HARTSOCK FOR OBG MANAGEMENT

Intrauterine adhesions from D&C after pregnancy loss are not uncommon. A 2014 meta-analysis of 10 prospective studies including 912 women reported a pooled prevalence for intrauterine adhesions of 19.1% (95% confidence interval [CI], 12.8–27.5) on hysteroscopic evaluation within 12 months following curettage.¹⁰ Once formed, these adhesions are associated with long-term impairment in reproductive outcomes, regardless of if they were treated or not. In a long-term follow-up study of women with and without adhesions after recurrent D&C for miscarriage, women with treated adhesions reported lower live birth rates, longer time to pregnancy, higher rates of preterm birth and higher rates of peripartum complications compared with those without adhesions.¹¹

Compared with curettage, hysteroscopy affords the surgeon complete visualization of the uterine cavity and tissue to be resected. This, in turn, minimizes trauma to the surrounding uterine cavity, minimizes the potential for post-procedural adhesion formation and their associated sequelae, and maximizes complete resection of tissue. Those treated with D&C appear to be significantly more likely to have adhesions than those treated via a hysteroscopic approach (30% vs 13%).¹²

Retained products of conception. Classically, a “gritty” sensation of the endometrium following evacuation of the uterus with a sharp curette has been used to indicate complete removal of tissue. The evolution from a nonvisualized procedure to ultrasound-guided vacuum aspiration of 1st trimester pregnancy tissue has been associated with a decreased risk of procedural complications and retained products of conception.¹³ However, even with intraoperative imaging, the risk of retained products of conception remains because it can be difficult to distinguish a small blood clot from retained pregnancy tissue on ultrasonography.

Retained pregnancy tissue can result in abnormal or heavy bleeding, require additional medical or surgical intervention, and is associated with endometrial inflammation and infection. Approximately 1 in every 4 women undergoing hysteroscopic resection of retained products are found to have evidence of endometritis in the resected tissue.¹⁴ This number is even higher in women with a diagnosis of recurrent pregnancy loss (62%).¹⁵

These complications from retained products of conception can be avoided with the hysteroscopic approach due to the direct visualization of the tissue removal. This benefit may be particularly beneficial in patients with known abnormal uterine cavities, such as those with Müllerian anomalies, uterine leiomyomas, preexisting adhesions, and history of placenta accreta spectrum disorder.

Continue to: Maximizing diagnostic yield...

Maximizing diagnostic yield

Many patients prefer surgical management of a missed abortion not for the procedural advantages, but to assist with tissue collection for cytogenetic testing of the pregnancy tissue. Given that embryonic chromosomal aneuploidy is implicated in 70% of miscarriages prior to 20 weeks’ gestation, genetic evaluation of the products of conception is commonly performed to identify a potential cause for the miscarriage.¹⁶ G-band karyotype is the most commonly performed genetic evaluation. Karyotype requires culturing of pregnancy tissue for 7-14 days to produce metaphase cells that are then chemically treated to arrest them at their maximally contracted stage. Cytogenetic evaluation is often curtailed when nonviable cells from products of conception fail to culture due to either time elapsed from diagnosis to demise or damage from tissue handling. Careful, directly observed tissue handling via a hysteroscopic approach may alleviate culture failure secondary to tissue damage.

Another concern with cultures of products of conception is the potential for maternal cell contamination. Early studies from the 1970s noted a significant skew toward 46, XX karyotype results in miscarried tissue as compared with 46, XY results. It was not until microsatellite analysis technology was available that it was determined that the result was due to analysis of maternal cells instead of products of conception.¹⁷ A 2014 study by Levy and colleagues and another by Lathi and colleagues that utilized single-nucleotide polymorphism (SNP) microarray found that maternal cell contamination affected 22% of all miscarriage samples analyzed and over half of karyotypes with a 46, XX result.^18,19

Traditional “blind” suction and curettage may inadvertently collect maternal endometrial tissue and contaminate the culture of fetal cells, limiting the validity of karyotype for products of conception.²⁰ The hysteroscopic approach may provide a higher diagnostic yield for karyotype analysis of fetal tissue by the nature of targeted tissue sampling under direct visualization, minimizing maternal cell contamination. One retrospective study by Cholkeri-Singh and colleagues evaluated rates of fetal chromosome detection without maternal contamination in a total of 264 patients undergoing either suction curettage or hysteroscopic resection. They found that fetal chromosomal detection without contamination was significantly higher in the hysteroscopy group compared with the suction curettage group (88.5 vs 64.8%, P< .001).²¹ Additionally, biopsies of tissue under direct visualization may enable the diagnosis of a true placental mosaicism and the study of the individual karyotype of each embryo in dizygotic twin missed abortions.

Finally, a hysteroscopic approach may afford the opportunity to also perform morphologic evaluation of the intact early fetus furthering the diagnostic utility of the procedure. With hysteroscopy, the gestational sac is identified and carefully entered, allowing for complete visualization of the early fetus and assessment of anatomic malformations that may provide insight into the pregnancy loss (ie, embryoscopy). In one series of 272 patients with missed abortions, while nearly 75% of conceptuses had abnormal karyotypes, 18% were found to have gross morphologic defects with a normal karyotype.²²

Bottom line

When faced with a patient with an early pregnancy loss, physicians should consider the decreased iatrogenic risks and improved diagnostic yield when deciding between D&C versus hysteroscopy for surgical management. There are certain patients with pre-existing risk factors that may stand to benefit the most (TABLE 2). Much like the opening case, those at risk for intrauterine adhesions, retained products of conception, or in whom a successful and accurate cytogenetic analysis is essential are the most likely to benefit from a hysteroscopic approach. The hysteroscopic approach also affords concurrent diagnosis and treatment of intrauterine pathology, such as leiomyomas and uterine septum, which are encountered approximately 12.5% of the time after one miscarriage and 29.4% of the time in patients with a history of more than one miscarriage.¹⁰ In the appropriately counseled patient and clinical setting, clinicians could also perform definitive surgical management during the same hysteroscopy. Finally, evaluation of the morphology of the demised fetus may provide additional information for patient counseling in those with euploid pregnancy losses.

CASE Resolved

Ultimately, our patient underwent complete hysteroscopic resection of the pregnancy tissue, which confirmed both a morphologically abnormal fetus and a 45, X karyotype of the products of conception. ●

Knowledge of the latest evidence on the management of pelvic floor disorders is essential for all practicing ObGyns. In this Update, we review long-term outcomes for a polyacrylamide hydrogel urethral bulking agent for the treatment of stress urinary incontinence (SUI) that presents a viable alternative to the gold standard, midurethral sling. We review the new recommendations from the American Urogynecologic Society (AUGS) regarding the administration of anticholinergics, highlighting a paradigm shift in the management of overactive bladder (OAB). In addition, we present data on a proposed threshold glycosylated hemoglobin A_1c (HbA_1c) level for patients undergoing pelvic organ prolapse (POP) surgery that may help reduce the risk of perioperative complications. Finally, we consider new evidence on the long-term efficacy and safety of transvaginal mesh for repair of POP.

Periurethral injection with  polyacrylamide hydrogel is a  long-term durable and safe  option for women with SUI

Brosche T, Kuhn A, Lobodasch K, et al. Seven-year efficacy and safety outcomes of Bulkamid for the treatment of stress urinary incontinence. Neurourol Urodyn. 2021;40:502-508. doi:10.1002/nau.24589.

Urethral bulking agents are a less invasive management option for women with SUI compared with the gold standard, midurethral sling. Treatment with a polyacrylamide hydrogel (PAHG; Bulkamid)—a nonparticulate hydrogel bulking agent—showed long-term efficacy and a favorable safety profile at 7 years’ follow-up.

Study details

Brosche and colleagues conducted a retrospective cohort study that included women with SUI or stress-predominant mixed urinary incontinence (MUI) who underwent transurethral PAHG injections for primary treatment of their incontinence symptoms. The study objective was to evaluate the long-term efficacy of PAHG based on patient satisfaction. Treatment safety was a secondary outcome.

Pad counts and validated questionnaires were used to determine treatment effectiveness. Additional data on reinjection rates, perioperative complications, and postoperative complications also were collected.

Long-term outcomes favorable

During the study time period, 1,200 patients were treated with PAHG, and 7-year data were available for 553 women. Of the 553 patients, 67% reported improvement or cure of their SUI symptoms when PAHG was performed as a primary procedure, consistent with previously published 12-month data. There were no perioperative complications. Postoperative complications were transient. Short-term subjective prolonged bladder emptying was the most common complication and occurred in 15% of patients.

Continue to: New society guidance...

New society guidance on the use  of anticholinergic medications  for the treatment of OAB

AUGS Clinical Consensus Statement: Association of anticholinergic medication use and cognition in women with overactive bladder. Female Pelvic Med Reconstr Surg. 2021;27:69-71. doi:10.1097/ SPV.0000000000001008.

In 2021, AUGS updated its consensus statement on the use of anticholinergic medications for the treatment of OAB. This action was in response to growing evidence that supports the association of anticholinergic medications with long-term cognitive adverse effects, including cognitive impairment, dementia, and Alzheimer disease.

Here, we summarize the most recent modifications, which differentiate the updated statement from the preceding consensus document published in 2017.

Updated AUGS recommendations

• If considering anticholinergic medications, counsel patients about the risk of cognitive adverse effects and weigh these risks against the potential benefits to their quality of life and overall health.
• Use the lowest possible dose when prescribing anticholinergics and consider alternatives such as β3 agonists (for example, mirabegron or vibegron).
• Avoid using anticholinergic medications in women older than age 70. However, if an anticholinergic must be used, consider a medication that has low potential to cross the blood-brain barrier (for example, trospium).

 HbA_1c levels > 8% may increase complications risk in urogyn surgery

Ringel NE, de Winter KL, Siddique M, et al. Surgical outcomes in urogynecology—assessment of perioperative and postoperative complications relative to preoperative hemoglobin A1c—a Fellows Pelvic Research Network study. Female Pelvic Med Reconstr Surg. 2022;28:7-13. doi:10.1097/ SPV.0000000000001057.

Diabetes mellitus is a known risk factor for complications following surgery. Adoption of an HbA_1c level threshold for risk stratification before urogynecologic surgery may help improve patient outcomes.

Study details

Ringel and colleagues conducted a multicenter retrospective cohort study that included women with diabetes mellitus who underwent prolapse and/or SUI surgery between 2013 and 2018. The aim of the study was to identify a hemoglobin A_1C threshold that would help predict increased risk for perioperative complications in women undergoing pelvic reconstructive surgery. Demographics, preoperative HbA_1c levels, and surgical data were collected.

Complication risks correlated with higher HbA_1c threshold

The study included 807 women with HbA_1c values that ranged from 5% to 12%. The overall complication rate was 44%. Sensitivity analysis was performed to compare complication rates between patients with varying HbA_1c levels and determine a threshold HbA_1c value with the greatest difference in complication rates.

The authors concluded that women with an HbA_1c level ≥ 8% showed the greatest increase of perioperative complications. Patients with an HbA_1c ≥ 8%, compared with those who had an HbA_1c < 8%, had a statistically significantly increased rate of overall (58% vs 42%, P = .002) and severe (27% vs 13%, P< .001) perioperative complications.

After multivariate logistic regression, the risk of overall complications remained elevated, with a 1.9-times higher risk of perioperative complications for women with an HbA_1c ≥ 8%.

Continue to:  Success is similar for TV mesh  and native tissue repair...

Success is similar for TV mesh  and native tissue repair

Kahn B, Varner RE, Murphy M, et al. Transvaginal mesh compared with native tissue repair for pelvic organ prolapse. Obstet Gynecol. 2022;139:975-985. doi:10.1097/AOG.0000000000004794.

The distribution of vaginal mesh kits for the repair of POP was halted by the US Food and Drug Administration (FDA) in 2019. However, concerns have been raised about the measures used by the FDA to justify pulling these devices from the market. A cohort study compared 36-month outcomes between women who underwent prolapse repair with newer generation transvaginal mesh versus native tissue repair.

Study details

In a nonrandomized prospective multicenter cohort study, Kahn and colleagues compared outcomes in women with POP who underwent native tissue repair or transvaginal mesh repair with the Uphold LITE vaginal support system. The study’s objective was to compare the safety and efficacy of native tissue and transvaginal mesh prolapse repairs at 36 months postoperatively.

Treatment success was measured based on composite and individual measures of anatomic and subjective success, need for retreatment, and the occurrence of adverse events. Quality of life (QoL) measures also were obtained using validated questionnaires. Intention-to-treat and per-protocol analyses were performed.

Composite success rate was higher for mesh repair

A total of 710 patients were screened for eligibility (225 received transvaginal mesh and 485 received native tissue repair). Transvaginal mesh placement was found to be significantly superior to native tissue repair for composite success (84% vs 73%, P = .009) when prolapse within the hymen (that is, Ba and/or C < 0 on the Pelvic Organ Prolapse Quantification System) was used to define anatomic success.

Adverse events were similar between transvaginal mesh and native tissue repair groups, with most adverse events occurring within the first 6 months. The mesh exposure rate was 4.9%. Of the 13 incidents of mesh exposure, 4 patients required surgical intervention and 1 incident was considered a serious adverse event. QoL measures demonstrated improvement without any statistically significant differences between the treatment cohorts. ●

Knowledge of the latest evidence on the management of pelvic floor disorders is essential for all practicing ObGyns. In this Update, we review long-term outcomes for a polyacrylamide hydrogel urethral bulking agent for the treatment of stress urinary incontinence (SUI) that presents a viable alternative to the gold standard, midurethral sling. We review the new recommendations from the American Urogynecologic Society (AUGS) regarding the administration of anticholinergics, highlighting a paradigm shift in the management of overactive bladder (OAB). In addition, we present data on a proposed threshold glycosylated hemoglobin A_1c (HbA_1c) level for patients undergoing pelvic organ prolapse (POP) surgery that may help reduce the risk of perioperative complications. Finally, we consider new evidence on the long-term efficacy and safety of transvaginal mesh for repair of POP.

Periurethral injection with  polyacrylamide hydrogel is a  long-term durable and safe  option for women with SUI

Brosche T, Kuhn A, Lobodasch K, et al. Seven-year efficacy and safety outcomes of Bulkamid for the treatment of stress urinary incontinence. Neurourol Urodyn. 2021;40:502-508. doi:10.1002/nau.24589.

Urethral bulking agents are a less invasive management option for women with SUI compared with the gold standard, midurethral sling. Treatment with a polyacrylamide hydrogel (PAHG; Bulkamid)—a nonparticulate hydrogel bulking agent—showed long-term efficacy and a favorable safety profile at 7 years’ follow-up.

Study details

Brosche and colleagues conducted a retrospective cohort study that included women with SUI or stress-predominant mixed urinary incontinence (MUI) who underwent transurethral PAHG injections for primary treatment of their incontinence symptoms. The study objective was to evaluate the long-term efficacy of PAHG based on patient satisfaction. Treatment safety was a secondary outcome.

Pad counts and validated questionnaires were used to determine treatment effectiveness. Additional data on reinjection rates, perioperative complications, and postoperative complications also were collected.

Long-term outcomes favorable

During the study time period, 1,200 patients were treated with PAHG, and 7-year data were available for 553 women. Of the 553 patients, 67% reported improvement or cure of their SUI symptoms when PAHG was performed as a primary procedure, consistent with previously published 12-month data. There were no perioperative complications. Postoperative complications were transient. Short-term subjective prolonged bladder emptying was the most common complication and occurred in 15% of patients.

Continue to: New society guidance...

New society guidance on the use  of anticholinergic medications  for the treatment of OAB

AUGS Clinical Consensus Statement: Association of anticholinergic medication use and cognition in women with overactive bladder. Female Pelvic Med Reconstr Surg. 2021;27:69-71. doi:10.1097/ SPV.0000000000001008.

In 2021, AUGS updated its consensus statement on the use of anticholinergic medications for the treatment of OAB. This action was in response to growing evidence that supports the association of anticholinergic medications with long-term cognitive adverse effects, including cognitive impairment, dementia, and Alzheimer disease.

Here, we summarize the most recent modifications, which differentiate the updated statement from the preceding consensus document published in 2017.

Updated AUGS recommendations

• If considering anticholinergic medications, counsel patients about the risk of cognitive adverse effects and weigh these risks against the potential benefits to their quality of life and overall health.
• Use the lowest possible dose when prescribing anticholinergics and consider alternatives such as β3 agonists (for example, mirabegron or vibegron).
• Avoid using anticholinergic medications in women older than age 70. However, if an anticholinergic must be used, consider a medication that has low potential to cross the blood-brain barrier (for example, trospium).

 HbA_1c levels > 8% may increase complications risk in urogyn surgery

Ringel NE, de Winter KL, Siddique M, et al. Surgical outcomes in urogynecology—assessment of perioperative and postoperative complications relative to preoperative hemoglobin A1c—a Fellows Pelvic Research Network study. Female Pelvic Med Reconstr Surg. 2022;28:7-13. doi:10.1097/ SPV.0000000000001057.

Diabetes mellitus is a known risk factor for complications following surgery. Adoption of an HbA_1c level threshold for risk stratification before urogynecologic surgery may help improve patient outcomes.

Study details

Ringel and colleagues conducted a multicenter retrospective cohort study that included women with diabetes mellitus who underwent prolapse and/or SUI surgery between 2013 and 2018. The aim of the study was to identify a hemoglobin A_1C threshold that would help predict increased risk for perioperative complications in women undergoing pelvic reconstructive surgery. Demographics, preoperative HbA_1c levels, and surgical data were collected.

Complication risks correlated with higher HbA_1c threshold

The study included 807 women with HbA_1c values that ranged from 5% to 12%. The overall complication rate was 44%. Sensitivity analysis was performed to compare complication rates between patients with varying HbA_1c levels and determine a threshold HbA_1c value with the greatest difference in complication rates.

The authors concluded that women with an HbA_1c level ≥ 8% showed the greatest increase of perioperative complications. Patients with an HbA_1c ≥ 8%, compared with those who had an HbA_1c < 8%, had a statistically significantly increased rate of overall (58% vs 42%, P = .002) and severe (27% vs 13%, P< .001) perioperative complications.

After multivariate logistic regression, the risk of overall complications remained elevated, with a 1.9-times higher risk of perioperative complications for women with an HbA_1c ≥ 8%.

Continue to:  Success is similar for TV mesh  and native tissue repair...

Success is similar for TV mesh  and native tissue repair

Kahn B, Varner RE, Murphy M, et al. Transvaginal mesh compared with native tissue repair for pelvic organ prolapse. Obstet Gynecol. 2022;139:975-985. doi:10.1097/AOG.0000000000004794.

The distribution of vaginal mesh kits for the repair of POP was halted by the US Food and Drug Administration (FDA) in 2019. However, concerns have been raised about the measures used by the FDA to justify pulling these devices from the market. A cohort study compared 36-month outcomes between women who underwent prolapse repair with newer generation transvaginal mesh versus native tissue repair.

Study details

In a nonrandomized prospective multicenter cohort study, Kahn and colleagues compared outcomes in women with POP who underwent native tissue repair or transvaginal mesh repair with the Uphold LITE vaginal support system. The study’s objective was to compare the safety and efficacy of native tissue and transvaginal mesh prolapse repairs at 36 months postoperatively.

Treatment success was measured based on composite and individual measures of anatomic and subjective success, need for retreatment, and the occurrence of adverse events. Quality of life (QoL) measures also were obtained using validated questionnaires. Intention-to-treat and per-protocol analyses were performed.

Composite success rate was higher for mesh repair

A total of 710 patients were screened for eligibility (225 received transvaginal mesh and 485 received native tissue repair). Transvaginal mesh placement was found to be significantly superior to native tissue repair for composite success (84% vs 73%, P = .009) when prolapse within the hymen (that is, Ba and/or C < 0 on the Pelvic Organ Prolapse Quantification System) was used to define anatomic success.

Adverse events were similar between transvaginal mesh and native tissue repair groups, with most adverse events occurring within the first 6 months. The mesh exposure rate was 4.9%. Of the 13 incidents of mesh exposure, 4 patients required surgical intervention and 1 incident was considered a serious adverse event. QoL measures demonstrated improvement without any statistically significant differences between the treatment cohorts. ●

Knowledge of the latest evidence on the management of pelvic floor disorders is essential for all practicing ObGyns. In this Update, we review long-term outcomes for a polyacrylamide hydrogel urethral bulking agent for the treatment of stress urinary incontinence (SUI) that presents a viable alternative to the gold standard, midurethral sling. We review the new recommendations from the American Urogynecologic Society (AUGS) regarding the administration of anticholinergics, highlighting a paradigm shift in the management of overactive bladder (OAB). In addition, we present data on a proposed threshold glycosylated hemoglobin A_1c (HbA_1c) level for patients undergoing pelvic organ prolapse (POP) surgery that may help reduce the risk of perioperative complications. Finally, we consider new evidence on the long-term efficacy and safety of transvaginal mesh for repair of POP.

Periurethral injection with  polyacrylamide hydrogel is a  long-term durable and safe  option for women with SUI

Brosche T, Kuhn A, Lobodasch K, et al. Seven-year efficacy and safety outcomes of Bulkamid for the treatment of stress urinary incontinence. Neurourol Urodyn. 2021;40:502-508. doi:10.1002/nau.24589.

Urethral bulking agents are a less invasive management option for women with SUI compared with the gold standard, midurethral sling. Treatment with a polyacrylamide hydrogel (PAHG; Bulkamid)—a nonparticulate hydrogel bulking agent—showed long-term efficacy and a favorable safety profile at 7 years’ follow-up.

Study details

Brosche and colleagues conducted a retrospective cohort study that included women with SUI or stress-predominant mixed urinary incontinence (MUI) who underwent transurethral PAHG injections for primary treatment of their incontinence symptoms. The study objective was to evaluate the long-term efficacy of PAHG based on patient satisfaction. Treatment safety was a secondary outcome.

Pad counts and validated questionnaires were used to determine treatment effectiveness. Additional data on reinjection rates, perioperative complications, and postoperative complications also were collected.

Long-term outcomes favorable

During the study time period, 1,200 patients were treated with PAHG, and 7-year data were available for 553 women. Of the 553 patients, 67% reported improvement or cure of their SUI symptoms when PAHG was performed as a primary procedure, consistent with previously published 12-month data. There were no perioperative complications. Postoperative complications were transient. Short-term subjective prolonged bladder emptying was the most common complication and occurred in 15% of patients.

Continue to: New society guidance...

New society guidance on the use  of anticholinergic medications  for the treatment of OAB

AUGS Clinical Consensus Statement: Association of anticholinergic medication use and cognition in women with overactive bladder. Female Pelvic Med Reconstr Surg. 2021;27:69-71. doi:10.1097/ SPV.0000000000001008.

In 2021, AUGS updated its consensus statement on the use of anticholinergic medications for the treatment of OAB. This action was in response to growing evidence that supports the association of anticholinergic medications with long-term cognitive adverse effects, including cognitive impairment, dementia, and Alzheimer disease.

Here, we summarize the most recent modifications, which differentiate the updated statement from the preceding consensus document published in 2017.

Updated AUGS recommendations

• If considering anticholinergic medications, counsel patients about the risk of cognitive adverse effects and weigh these risks against the potential benefits to their quality of life and overall health.
• Use the lowest possible dose when prescribing anticholinergics and consider alternatives such as β3 agonists (for example, mirabegron or vibegron).
• Avoid using anticholinergic medications in women older than age 70. However, if an anticholinergic must be used, consider a medication that has low potential to cross the blood-brain barrier (for example, trospium).

 HbA_1c levels > 8% may increase complications risk in urogyn surgery

Ringel NE, de Winter KL, Siddique M, et al. Surgical outcomes in urogynecology—assessment of perioperative and postoperative complications relative to preoperative hemoglobin A1c—a Fellows Pelvic Research Network study. Female Pelvic Med Reconstr Surg. 2022;28:7-13. doi:10.1097/ SPV.0000000000001057.

Diabetes mellitus is a known risk factor for complications following surgery. Adoption of an HbA_1c level threshold for risk stratification before urogynecologic surgery may help improve patient outcomes.

Study details

Ringel and colleagues conducted a multicenter retrospective cohort study that included women with diabetes mellitus who underwent prolapse and/or SUI surgery between 2013 and 2018. The aim of the study was to identify a hemoglobin A_1C threshold that would help predict increased risk for perioperative complications in women undergoing pelvic reconstructive surgery. Demographics, preoperative HbA_1c levels, and surgical data were collected.

Complication risks correlated with higher HbA_1c threshold

The study included 807 women with HbA_1c values that ranged from 5% to 12%. The overall complication rate was 44%. Sensitivity analysis was performed to compare complication rates between patients with varying HbA_1c levels and determine a threshold HbA_1c value with the greatest difference in complication rates.

The authors concluded that women with an HbA_1c level ≥ 8% showed the greatest increase of perioperative complications. Patients with an HbA_1c ≥ 8%, compared with those who had an HbA_1c < 8%, had a statistically significantly increased rate of overall (58% vs 42%, P = .002) and severe (27% vs 13%, P< .001) perioperative complications.

After multivariate logistic regression, the risk of overall complications remained elevated, with a 1.9-times higher risk of perioperative complications for women with an HbA_1c ≥ 8%.

Continue to:  Success is similar for TV mesh  and native tissue repair...

Success is similar for TV mesh  and native tissue repair

Kahn B, Varner RE, Murphy M, et al. Transvaginal mesh compared with native tissue repair for pelvic organ prolapse. Obstet Gynecol. 2022;139:975-985. doi:10.1097/AOG.0000000000004794.

The distribution of vaginal mesh kits for the repair of POP was halted by the US Food and Drug Administration (FDA) in 2019. However, concerns have been raised about the measures used by the FDA to justify pulling these devices from the market. A cohort study compared 36-month outcomes between women who underwent prolapse repair with newer generation transvaginal mesh versus native tissue repair.

Study details

In a nonrandomized prospective multicenter cohort study, Kahn and colleagues compared outcomes in women with POP who underwent native tissue repair or transvaginal mesh repair with the Uphold LITE vaginal support system. The study’s objective was to compare the safety and efficacy of native tissue and transvaginal mesh prolapse repairs at 36 months postoperatively.

Treatment success was measured based on composite and individual measures of anatomic and subjective success, need for retreatment, and the occurrence of adverse events. Quality of life (QoL) measures also were obtained using validated questionnaires. Intention-to-treat and per-protocol analyses were performed.

Composite success rate was higher for mesh repair

A total of 710 patients were screened for eligibility (225 received transvaginal mesh and 485 received native tissue repair). Transvaginal mesh placement was found to be significantly superior to native tissue repair for composite success (84% vs 73%, P = .009) when prolapse within the hymen (that is, Ba and/or C < 0 on the Pelvic Organ Prolapse Quantification System) was used to define anatomic success.

Adverse events were similar between transvaginal mesh and native tissue repair groups, with most adverse events occurring within the first 6 months. The mesh exposure rate was 4.9%. Of the 13 incidents of mesh exposure, 4 patients required surgical intervention and 1 incident was considered a serious adverse event. QoL measures demonstrated improvement without any statistically significant differences between the treatment cohorts. ●

Cesarean birth is one of the most common major surgical procedures performed in developed countries¹ with over 1,170,000 cesarean births in the United States in 2021.² Many surgeons and anesthesiologists believe that Enhanced Recovery after Surgery (ERAS) pathways improve surgical outcomes.^3,4 Important goals of ERAS include setting patient expectations for the surgical procedure, accelerating patient recovery to full function, and minimizing perioperative complications such as severe nausea, aspiration, surgical site infection, wound complications, and perioperative anemia. The ERAS Society in 2018^5-7 and the Society for Obstetric Anesthesia and Perinatology (SOAP) in 2021⁸ proposed ERAS pathways for cesarean birth. Both societies recommended that obstetric units consider adopting an ERAS pathway compatible with local clinical resources. In addition, the American College of Obstetricians and Gynecologists (ACOG) has provided guidance for implementing ERAS pathways for gynecologic surgery.⁹ The consistent use of standardized protocols to improve surgical care in obstetrics should lead to a reduction in care variation and improve health equity outcomes.

The clinical interventions recommended for ERAS cesarean birth occur sequentially in the preoperative, intraoperative, and postoperative phases of care. The recommendations associated with each of these phases are reviewed below. It is important to note that each obstetric unit should use a multidisciplinary process to develop an ERAS pathway that best supports local practice given clinician preferences, patient characteristics, and resource availability.
 

Preoperative components of ERAS

Standardized patient education (SPE). SPE is an important component of ERAS, although evidence to support the recommendation is limited. At a minimum a written handout describing steps in the cesarean birth process, or a patient-education video should be part of patient education. The University of Michigan Medical Center has produced a 3-minute video for patients explaining ERAS cesarean birth.¹⁰ The University of Maryland Medical Center has produced a 2.5-minute video in English and Spanish, explaining ERAS cesarean birth for patients.¹¹ Some surgeons place a telephone call to patients the evening before surgery to help orient the patient to ERAS cesarean birth.

Breastfeeding education. An important goal of obstetric care is to optimize the rate of exclusive breastfeeding at birth. Breastfeeding education, including a commitment to support the initiation of breastfeeding within 1 hour of birth, may enhance the rate of exclusive breastfeeding. There are numerous videos available for patients about breastfeeding after cesarean birth (as an example, see: https://www.youtube.com/watch?v=9iOGn85NdTg).

Limit fasting. In the past, surgical guidelines recommended fasting after midnight prior to surgery. The ERAS Society recommends that patients should be encouraged to drink clear fluids up to 2 hours before surgery and may have a light meal up to 6 hours before surgery (Part 1).

Carbohydrate loading. Surgery causes a metabolic stress that is increased by fasting. Carbohydrate loading prior to surgery reduces the magnitude of the catabolic state caused by the combination of surgery and fasting.¹² SOAP and the ERAS Society recommend oral carbohydrate fluid supplementation 2 hours before surgery for nondiabetic patients. SOAP suggests 32 oz of Gatorade or 16 oz of clear apple juice as options for carbohydrate loading. For diabetic patients, the carbohydrate load can be omitted. In fasting pregnant patients at term, gastric emptying was near complete 2 hours after consumption of 400 mL of a carbohydrate drink.¹³ In one study, consumption of 400 mL of a carbohydrate drink 2 hours before cesarean resulted in a 7% increase in the newborn blood glucose level at 20 min after delivery.¹⁴

Minimize preoperative anemia. Approximately 50% of pregnant women are iron deficient and approximately 10% are anemic in the third trimester.^15,16 Cesarean birth is associated with significant blood loss necessitating the need to optimize red blood cell mass before surgery. Measuring ferritin to identify patients with iron deficiency and aggressive iron replacement, including intravenous iron if necessary, will reduce the prevalence of anemia prior to cesarean birth.¹⁷ Another cause of anemia in pregnancy is vitamin B12 (cobalamin) deficiency. Low vitamin B12 is especially common in pregnant patients who have previously had bariatric surgery. One study reported that, of 113 pregnant patients who were, on average, 3 years from a bariatric surgery procedure, 12% had vitamin B12 circulating levels < 130 pg/mL.¹⁸ Among pregnant patients who are anemic, and do not have a hemoglobinopathy, measuring ferritin, folic acid, and vitamin B12 will help identify the cause of anemia and guide treatment.¹⁹

Optimize preoperative physical condition. Improving healthy behaviors and reducing unhealthy behaviors preoperatively may enhance patient recovery to full function. In the weeks before scheduled cesarean birth, cessation of the use of tobacco products, optimizing activity and improving diet quality, including increasing protein intake, may best prepare patients for the metabolic stress of surgery.

Continue to: Intraoperative components of ERAS...

Intraoperative components of ERAS

Reduce the risk of surgical site infection (SSI) and wound complications. Bundles that include antibiotics, chlorhexidine (or an alternative antibacterial soap) and clippers have been shown to reduce SSI.²⁰ Routine administration of preoperative antibiotics is a consensus recommendation and there is high adherence with this recommendation in the United States. Chlorhexidine-alcohol is the preferred solution for skin preparation. Vaginal preparation with povidine-iodine or chlorhexidine may be considered.⁶

Surgical technique. Blunt extension of a transverse hysterotomy may reduce blood loss. Closure of the hysterotomy incision in 2 layers is recommended to reduce uterine scar dehiscence in a subsequent pregnancy. If the patient has ≥2 cm of subcutaneous tissue, this layer should be approximated with sutures. Skin closure should be with subcuticular suture.⁶

Optimize uterotonic administration. Routine use of uterotonics reduces the risk of blood loss, transfusion, and postoperative anemia. There is high adherence with the use of uterotonic administration after birth in the United States.^6,8

Ensure normothermia. Many patients become hypothermic during a cesarean birth. Active warming of the patient with an in-line IV fluid warmer and forced air warming over the patient’s body can reduce the risk of hypothermia.⁸

Initiate multimodal anesthesia. Anesthesiologists often use intrathecal or epidural morphine to enhance analgesia. Ketorolac administration prior to completion of the cesarean procedure and perioperative administration of acetaminophen may reduce postoperative pain.⁸ The use of preoperative antiemetics will reduce intraoperative and postoperative nausea and vomiting.

Initiate VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁶

Postoperative components of ERAS

Patient education to prepare for discharge home when ready. Patient education focused on home when ready is important in preparing the patient for discharge home.⁷ Completion of required newborn testing, lactation education, and contraception planning plus coordination of newborn pediatric follow-up is necessary before discharge.

Support early return of bowel function. Early return of bowel function is best supported by a multimodal approach including initiation of clear fluid intake immediately following surgery, encouraging consumption of a regular diet within 2⁷ to 4 hours⁸ following surgery. Gum chewing for at least 5 minutes 3 times daily accelerates return of bowel function.⁸ In a meta-analysis of 10 randomized studies examining the effect of gum chewing after cesarean, the investigators reported that gum chewing shortened the time to passage of flatus and defecation.²¹

Early ambulation.

Sequentially advanced activity, starting with sitting on the edge of the bed, sitting in a chair, and ambulation within 8 hours of surgery, is recommended to facilitate faster recovery, reduce rates of complications, and enable transition to home.⁸

Early removal of the urinary catheter. It is recommended that the urinary catheter be removed within 12 hours after cesarean birth.⁸ Early removal of the urinary catheter increases patient mobility and reduces the length of hospitalization. Early removal of the urinary catheter may be associated with postoperative urinary retention and recatheterization in a small number of patients.

Prescribe routinely scheduled acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and ketorolac. A key component of ERAS cesarean birth is the standardized administration of nonopioid pain medicines, alternating doses of acetaminophen and an NSAID. ERAS cesarean birth is likely to result in a reduction in inpatient and postdischarge opioid use.^22-24

VTE prophylaxis. Pneumatic compression stockings are recommended. Anticoagulation should not be routinely used for VTE prophylaxis.⁸

Auditing and reporting adherence with components of ERAS

In clinical practice there may be a gap between a clinician’s subjective perception of their performance and an independent audit of their clinical performance. ERAS pathways should be implemented with a commitment to performing audits and providing quantitative feedback to clinicians. Consistent use of measurement, feedback, and coaching can improve performance and reduce variation among individual clinicians. As an example, in one study of the use of a surgical safety checklist, 99% of the surgeons reported that they routinely used a surgical safety checklist, but the audit showed that the checklist was used in only 60% of cases.²⁵ Gaps between self-reported performance and audited performance are common in clinical practice. Audits with feedback are critical to improving adherence with the components of an ERAS pathway.

Three independent systematic reviews and meta-analyses report that ERAS pathways reduce hospital length of stay without increasing the readmission rate.^26-28 One meta-analysis reported that ERAS may also reduce time to first mobilization and result in earlier removal of the urinary catheter.²⁶ ERAS pathways also may reduce postoperative complications, lower pain scores, and decrease opioid use.²⁷ The general consensus among quality and safety experts is that reducing variation through standardization of pathways is generally associated with improved quality and enhanced safety. ERAS pathways have been widely accepted in multiple surgical fields. ERAS pathways should become the standard for performing cesarean procedures.●