OBG Management

EXPERT COMMENTARY

Ezeh and colleagues conducted a retrospective analysis to evaluate the effectiveness of long-term combination suppressive therapy on hirsutism, acne, and menstrual disturbances in patients with PCOS and to identify the elements that could predict therapeutic response.

Details of the study

This chart review examined data from 200 nondiabetic patients with PCOS who presented between October 1987 and June 2002. PCOS diagnosis was based on the National Institutes of Health (NIH) 1990 criteria. During the initial visit, patients underwent a detailed medical history and physical exam, including a modified Ferriman-Gallwey hirsutism score and hormonal evaluation.

Treatment regimens. Patients were treated with suppressive therapy that consisted of an oral contraceptive (OC) (35 µg ethinyl estradiol plus 1 mg ethynodiol diacetate), an antiandrogen (spironolactone 200 mg/day), or a combination of these drugs. They were followed every 4 to 12 months (mean follow-up time, 34.2 months; range, 6–155 months), and subjective therapy response was assessed from medical records and by improvements in hirsutism scores.

Study findings. The 138 patients treated with combination suppressive therapy reported higher rates of subjective improvement in hirsutism compared with patients treated with other regimens (89.9% vs 72.0%, P<.0001). They also had a significant objective reduction in their modified Ferriman-Gallwey hirsutism score (6.0 vs 3.2; P = .0001). The combination therapy was superior to either regimen alone; the response to therapy for symptom resolution took at least 6 months and continued for up to 60 months of combination suppressive therapy.

Adding electrolysis treatment to the combination regimen resulted in improved patient satisfaction, but the differences were not significant. Patients’ satisfaction with the therapeutic response could be predicted from their pretreatment hirsutism scores or circulating sex hormone–binding globulin levels.

Study strengths and weaknesses

The study’s major strengths are the large number of patients included, the uniformity of criteria for diagnosis, and the prolonged follow-up. This is one of the few studies to report the impact of therapy on health-related quality of life in patients with PCOS and to assess response to therapy with use of objective measures, such as changes in the modified Ferriman-Gallwey score.

However, the criteria used to diagnose PCOS—the NIH 1990 criteria—currently are used less commonly than the Rotterdam 2003 criteria, and they are less inclusive for the diagnosis of PCOS.

The OC pill formulation used in this study contained the progestogen ethynodiol diacetate, which is not used routinely in modern clinical practice. In addition, the majority of patients were non-Hispanic white, which limits extrapolating these findings to other races and ethnicities.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Ezeh and colleagues conducted a retrospective analysis to evaluate the effectiveness of long-term combination suppressive therapy on hirsutism, acne, and menstrual disturbances in patients with PCOS and to identify the elements that could predict therapeutic response.

Details of the study

This chart review examined data from 200 nondiabetic patients with PCOS who presented between October 1987 and June 2002. PCOS diagnosis was based on the National Institutes of Health (NIH) 1990 criteria. During the initial visit, patients underwent a detailed medical history and physical exam, including a modified Ferriman-Gallwey hirsutism score and hormonal evaluation.

Treatment regimens. Patients were treated with suppressive therapy that consisted of an oral contraceptive (OC) (35 µg ethinyl estradiol plus 1 mg ethynodiol diacetate), an antiandrogen (spironolactone 200 mg/day), or a combination of these drugs. They were followed every 4 to 12 months (mean follow-up time, 34.2 months; range, 6–155 months), and subjective therapy response was assessed from medical records and by improvements in hirsutism scores.

Study findings. The 138 patients treated with combination suppressive therapy reported higher rates of subjective improvement in hirsutism compared with patients treated with other regimens (89.9% vs 72.0%, P<.0001). They also had a significant objective reduction in their modified Ferriman-Gallwey hirsutism score (6.0 vs 3.2; P = .0001). The combination therapy was superior to either regimen alone; the response to therapy for symptom resolution took at least 6 months and continued for up to 60 months of combination suppressive therapy.

Adding electrolysis treatment to the combination regimen resulted in improved patient satisfaction, but the differences were not significant. Patients’ satisfaction with the therapeutic response could be predicted from their pretreatment hirsutism scores or circulating sex hormone–binding globulin levels.

Study strengths and weaknesses

The study’s major strengths are the large number of patients included, the uniformity of criteria for diagnosis, and the prolonged follow-up. This is one of the few studies to report the impact of therapy on health-related quality of life in patients with PCOS and to assess response to therapy with use of objective measures, such as changes in the modified Ferriman-Gallwey score.

However, the criteria used to diagnose PCOS—the NIH 1990 criteria—currently are used less commonly than the Rotterdam 2003 criteria, and they are less inclusive for the diagnosis of PCOS.

The OC pill formulation used in this study contained the progestogen ethynodiol diacetate, which is not used routinely in modern clinical practice. In addition, the majority of patients were non-Hispanic white, which limits extrapolating these findings to other races and ethnicities.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Ezeh and colleagues conducted a retrospective analysis to evaluate the effectiveness of long-term combination suppressive therapy on hirsutism, acne, and menstrual disturbances in patients with PCOS and to identify the elements that could predict therapeutic response.

Details of the study

This chart review examined data from 200 nondiabetic patients with PCOS who presented between October 1987 and June 2002. PCOS diagnosis was based on the National Institutes of Health (NIH) 1990 criteria. During the initial visit, patients underwent a detailed medical history and physical exam, including a modified Ferriman-Gallwey hirsutism score and hormonal evaluation.

Treatment regimens. Patients were treated with suppressive therapy that consisted of an oral contraceptive (OC) (35 µg ethinyl estradiol plus 1 mg ethynodiol diacetate), an antiandrogen (spironolactone 200 mg/day), or a combination of these drugs. They were followed every 4 to 12 months (mean follow-up time, 34.2 months; range, 6–155 months), and subjective therapy response was assessed from medical records and by improvements in hirsutism scores.

Study findings. The 138 patients treated with combination suppressive therapy reported higher rates of subjective improvement in hirsutism compared with patients treated with other regimens (89.9% vs 72.0%, P<.0001). They also had a significant objective reduction in their modified Ferriman-Gallwey hirsutism score (6.0 vs 3.2; P = .0001). The combination therapy was superior to either regimen alone; the response to therapy for symptom resolution took at least 6 months and continued for up to 60 months of combination suppressive therapy.

Adding electrolysis treatment to the combination regimen resulted in improved patient satisfaction, but the differences were not significant. Patients’ satisfaction with the therapeutic response could be predicted from their pretreatment hirsutism scores or circulating sex hormone–binding globulin levels.

Study strengths and weaknesses

The study’s major strengths are the large number of patients included, the uniformity of criteria for diagnosis, and the prolonged follow-up. This is one of the few studies to report the impact of therapy on health-related quality of life in patients with PCOS and to assess response to therapy with use of objective measures, such as changes in the modified Ferriman-Gallwey score.

However, the criteria used to diagnose PCOS—the NIH 1990 criteria—currently are used less commonly than the Rotterdam 2003 criteria, and they are less inclusive for the diagnosis of PCOS.

The OC pill formulation used in this study contained the progestogen ethynodiol diacetate, which is not used routinely in modern clinical practice. In addition, the majority of patients were non-Hispanic white, which limits extrapolating these findings to other races and ethnicities.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Midlife woman with low libido causing distress

At her annual gynecologic visit, a 55-year-old woman notes that she has almost no interest in sex. In the past, her libido was good and relations were pleasurable. Since her mid-40s, she has noticed a gradual decline in libido and orgasmic response. Sexual frequency has declined from once or twice weekly to just a few times per month. She has been married for 25 years and describes the relationship as caring and strong. Her husband is healthy with a good libido; his intermittent erectile dysfunction is treated with a phosphodiesterase-5 inhibitor. The patient’s low libido is distressing, as the decline in sexual frequency is causing some conflict for the couple. She requests that her testosterone level be checked because she heard that treatment with testosterone cream will solve this problem.

Evaluating and treating low libido in menopausal women

Low libido is a very common sexual problem for women. When sexual problems are accompanied by distress, they are classified as sexual dysfunctions. Although ObGyns should discuss sexual concerns at every comprehensive visit, if the patient has no associated distress, treatment is not necessarily indicated. A woman with low libido or anorgasmia who is satisfied with her sex life and is not bothered by these issues does not require any intervention.

Currently, the only indication for testosterone therapy that is supported by clinical trial evidence is low sexual desire with associated distress, known as hypoactive sexual desire disorder (HSDD). Although other sexual problems also commonly occur in menopausal women, such as disorders of orgasm and pain, testosterone is not recommended for these problems. In addition, testosterone is not approved by the US Food and Drug Administration (FDA) for the treatment of female sexual dysfunction.

Routinely inquire about sexual functioning

Ask your patients about sexual concerns at every comprehensive visit. You can easily incorporate into the review of systems a general question, such as, “Do you have any sexual concerns?” If the patient does mention a sexual problem, schedule a separate visit (given appointment time constraints) to address it. History and physical examination information you gather during the comprehensive visit will be helpful in the subsequent problem-focused visit.

Taking a thorough history is key when addressing a patient’s sexual problems, since identifying possible etiologies guides treatment. Often, the cause of female sexual dysfunction is multifactorial and includes physiologic, psychologic, and relationship issues.

Explore potential causes, recommend standard therapies

Common causes of low libido in menopausal women include vasomotor symptoms, insomnia, urinary incontinence, cancer or another major medical problem, weight gain, poor body image, genitourinary syndrome of menopause (GSM) with dyspareunia, fatigue, stress, aging, relationship duration, lack of novelty, relationship conflict, and a partner’s sexual problems. Other common etiologies include depression, anxiety, and substance use disorders, as well as medications used to treat these disorders, including selective serotonin reuptake inhibitors (SSRIs).

Continue to: There are many effective therapies...

There are many effective therapies for low sexual desire to consider prior to initiating a trial of testosterone, which should be considered for HSDD only if the disorder persists after addressing all other possible contributing factors (TABLE 1).

Sex therapy, for example, provides information on sexual functioning and helps improve communication and mutual pleasure and satisfaction. Strongly encourage—if not require—a consultation with a sex therapist before prescribing testosterone for low libido. Any testosterone-derived improvement in sexual functioning will be enhanced by improved communication and additional strategies to achieve mutual pleasure.

Hormone therapy. Vasomotor symptoms, with their associated sleep disruption, fatigue, and reduced quality of life (QOL), often adversely impact sexual desire. Estrogen therapy does not appear to improve libido in otherwise asymptomatic women; however, in women with bothersome vasomotor symptoms treated with estrogen, sexual interest may increase as a result of improved sleep, fatigue, and overall QOL. The benefits of systemic hormone therapy generally outweigh its risks for most healthy women younger than age 60 who have bothersome hot flashes and night sweats.¹

Nonhormonal and other therapies. GSM with dyspareunia is a principal cause of sexual dysfunction in older women.² Many safe and effective treatments are available, including low-dose vaginal estrogen therapy, nonhormonal moisturizers and lubricants, ospemifene, vaginal dehydroepiandrosterone, and pelvic floor physical therapy.³ Urinary incontinence commonly occurs in midlife women and contributes to low libido.⁴

Lifestyle approaches. Address fatigue and stress by having the patient adjust her work and sleep schedules, obtain help with housework and meals, and engage in mind-body interventions, counseling, or yoga. Sexual function may benefit from yoga practice, likely as a result of the patient experiencing reduced stress and enhanced body image. Improving overall health and body image with regular exercise, optimal diet, and weight management may contribute to a more satisfying sex life after the onset of menopause.

Relationship refresh. Women’s sexual interest often declines with relationship duration, and both men and women who are in new relationships generally have increased libido, affirming the importance of novelty over the long term. Couples will benefit from “date nights,” weekends away from home, and trying novel positions, locations, and times for sex. Couple’s counseling may address relationship conflict.

Expert referral. Depression, anxiety, and substance use disorders are prevalent in menopausal women and contribute to sexual dysfunction. Effective therapy is available, although some pharmacologic treatments (including SSRIs) may be an additional cause of sexual dysfunction. In addition to recommending appropriate counseling and support, referring the patient to a psychopharmacologist with expertise in managing sexual adverse effects of medications may optimize care.

Continue to: Sexual function improves, but patient still wants to try testosterone

The patient returns for follow-up visits scheduled specifically to address her sexual concerns. Sex is more comfortable and pleasurable since initiating low-dose vaginal estrogen therapy. Having been on an SSRI since her mid-40s for mild depression, the patient switched to bupropion and notes improved libido and orgasmic response. She is exercising more regularly and working with a nutritionist to address a 15-lb weight gain after menopause. The couple saw a sex therapist and is communicating better about sex with more novelty in their repertoire. They are enjoying a regular date night. Although the patient’s sex life has improved with these interventions, she is still very interested in trying testosterone.

Testosterone’s effects on HSDD in menopausal women

After addressing the many factors that contribute to sexual disinterest, a trial of testosterone may be appropriate for a menopausal woman who continues to experience low libido with associated distress.

Testosterone levels decrease with aging in both men and women. Although testosterone levels decline by approximately 50% with bilateral oophorectomy, there is no decline in androgen levels with natural menopause.⁵ Testosterone circulates tightly bound to sex hormone–binding globulin (SHBG), so free or active testosterone will be reduced by oral estrogens, which increase SHBG levels.⁶ As most menopausal women will have a low testosterone level due to aging, measuring the testosterone level does not provide information about the etiology of the sexual problem.

Although some studies have identified an association between endogenous androgen levels and sexual function, the associations are modest and are of uncertain clinical significance.^7-9 Not surprisingly, other factors, such as physical and psychologic health and the quality of the relationship, often are reported as more important predictors of sexual satisfaction than androgen levels.¹⁰

While endogenous testosterone levels may not correlate with sexual function, clinical trials of carefully selected menopausal women with HSDD have shown that androgen treatment generally results in improved sexual function.¹¹ Studies demonstrate substantial improvements in sexual desire, orgasmic response, and frequency in menopausal women treated with high doses of intramuscular testosterone, which result in supraphysiologic androgen levels.^12,13 While it is interesting that women with testosterone levels in the male low range have sizeable increases in sexual desire and response, long-term use of high-dose testosterone would result in unacceptable androgenic adverse effects and risks.

Continue to: Testosterone in low doses...

Testosterone in low doses. It is more relevant to consider the impact on female sexual function of low doses of testosterone, which raise the reduced testosterone levels seen in older women to the higher levels seen in reproductive-aged women.

A series of double-blind, multicenter, randomized, placebo-controlled trials in menopausal women with HSDD examined the impact on sexual function of a transdermal testosterone patch (300 μg) that increased blood testosterone levels to the upper limit of normal for young women.^14-17 In these studies, compared with placebo, women using testosterone reported significant improvements in sexual desire, arousal, orgasmic response, frequency, and sexually related distress. Findings were consistent in surgically and naturally menopausal women, with and without the use of concurrent estrogen therapy. Improvements were clinically limited, however. On average, testosterone-treated women experienced 1 to 1.5 additional satisfying sexual events in a 4-week period compared with those treated with placebo. The percentage of women reporting a clinically meaningful benefit from treatment was significantly greater in women treated with testosterone (52%) compared with the placebo-treated women (31%).¹⁸ An appreciable placebo response was seen, typical of most studies of therapies for sexual dysfunction.

Safety concerns

Potential risks of testosterone treatment include acne, hirsutism, irreversible deepening of the voice, and adverse changes in lipids and liver function (TABLE 2).¹⁹ Adverse effects are dose dependent and are unlikely with physiologically dosed testosterone.

A 1-year study of testosterone patches in approximately 800 menopausal women with HSDD (with a subgroup of women followed for an additional year) provides the most comprehensive safety data available.¹⁷ Unwanted hair growth occurred more often in women receiving testosterone, without significant differences in blood biochemistry,hematologic parameters, carbohydrate metabolism, or lipids. Breast cancer was diagnosed in more women receiving testosterone than placebo. Although this finding may have been due to chance, the investigators concluded that long-term effects of testosterone treatment remain uncertain.

The FDA reviewed the data from the testosterone patch studies and determined that testosterone patches were effective for the treatment of HSDD in menopausal women, but more information was needed on long-term safety before approval could be granted. Another company then developed a testosterone gel product that produced similar blood levels as the testosterone patch. It was presumed that there would be similar efficacy; the principal goal of these studies was to examine long-term safety, particularly with respect to breast cancer and cardiovascular disease. Unexpectedly, although it raised testosterone blood levels to the upper limit of normal for young women, the testosterone gel product was no more effective than placebo.²⁰ The clinical trial was ended, with safety data never published.

Continue to: Availability of testosterone formulations

Currently, no androgen therapies are FDA approved for the treatment of female sexual dysfunction. Although the best evidence regarding testosterone efficacy and safety involves the use of testosterone patches (300 μg), appropriately dosed for women, these patches are not currently available. FDA-approved testosterone patches are approved for the treatment of male hypogonadism, but use of these patches in women is not recommended since they would result in very high circulating testosterone levels.

Testosterone subcutaneous implants, pellets, and intramuscular injections also are not recommended for women because of the risk of excessive dosing. Small trials of menopausal women taking oral estrogen with low sexual desire found that oral formulations of testosterone improved libido in this study population.²¹ The combination of esterified estrogens (0.625 mg) and methyltestosterone (1.25 mg) is available as a compounded, non-FDA approved product. Oral androgen formulations generally are not advised, due to potential adverse effects on lipids and liver function.²²

Compounded testosterone products. Ointments and creams may be compounded by prescription (TABLE 3). Product purity, dose, bioavailability, and quality typically are untested, and substantial variability exists between formulations and batches.²³ Applying 1% testosterone cream or gel (0.5 g/day) topically to the thigh or lower abdomen should increase the low testosterone levels typically seen in menopausal women to the higher levels seen in younger women.^24,25 Application to the vulva or vagina is not advised, as it may cause local irritation and is unpredictably absorbed.

Adapting male testosterone products. High-quality FDA-approved testosterone gel formulations are available for male hypogonadism. However, since women have approximately one-tenth the circulating testosterone levels of men, supraphysiologic dosing is a risk when these products are prescribed for women. Most testosterone products approved for men are provided in pumps or packets, and they are difficult to dose-adjust for women. Applying one-tenth the male dose of 1% testosterone gel (Testim), which comes in a resealable unit-dose tube, is an alternative to compounding. For men, the dose is 1 tube per day, so women should make 1 tube last for 10 days by using 3 to 4 drops of testosterone gel per day. Close physical contact must be avoided immediately after application, as topical hormone creams and gels are easily transferred to others. The safety and efficacy of compounded or dose-adjusted male testosterone products used in women are unknown.

Follow treated women closely. Women who elect to use transdermal testosterone therapy should be seen at 8 to 12 weeks to assess treatment response. Regular follow-up visits are required to assess response, satisfaction, and adverse effects, including acne and hirsutism. Since there may be little correlation between serum testosterone levels and the prescribed dose of a compounded testosterone product, testosterone levels should be measured regularly as a safety measure. The goal is to keep serum testosterone concentrations within the normal range for reproductive-aged women to reduce the likelihood of adverse effects. Testosterone levels should not be tested as an efficacy measure, however, as there is no testosterone level that will assure a satisfactory sex life.

CASE Conclusion

After a thorough discussion of high placebo response rates, potential adverse effects, unknown long-term risks, and off-label nature of testosterone use, the patient elects a trial of compounded 1% testosterone cream. Her clinician informs her of the limitations of compounded formulations and the need for regular testing of testosterone levels to prevent supraphysiologic dosing. At a follow-up visit 8 weeks later, she reports improved sexual desire and elects to continue treatment and monitoring. After using testosterone for 2 years, the patient is uncertain that she still is experiencing a significant benefit, stops testosterone treatment, and remains satisfied with her sex life.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Midlife woman with low libido causing distress

At her annual gynecologic visit, a 55-year-old woman notes that she has almost no interest in sex. In the past, her libido was good and relations were pleasurable. Since her mid-40s, she has noticed a gradual decline in libido and orgasmic response. Sexual frequency has declined from once or twice weekly to just a few times per month. She has been married for 25 years and describes the relationship as caring and strong. Her husband is healthy with a good libido; his intermittent erectile dysfunction is treated with a phosphodiesterase-5 inhibitor. The patient’s low libido is distressing, as the decline in sexual frequency is causing some conflict for the couple. She requests that her testosterone level be checked because she heard that treatment with testosterone cream will solve this problem.

Evaluating and treating low libido in menopausal women

Low libido is a very common sexual problem for women. When sexual problems are accompanied by distress, they are classified as sexual dysfunctions. Although ObGyns should discuss sexual concerns at every comprehensive visit, if the patient has no associated distress, treatment is not necessarily indicated. A woman with low libido or anorgasmia who is satisfied with her sex life and is not bothered by these issues does not require any intervention.

Currently, the only indication for testosterone therapy that is supported by clinical trial evidence is low sexual desire with associated distress, known as hypoactive sexual desire disorder (HSDD). Although other sexual problems also commonly occur in menopausal women, such as disorders of orgasm and pain, testosterone is not recommended for these problems. In addition, testosterone is not approved by the US Food and Drug Administration (FDA) for the treatment of female sexual dysfunction.

Routinely inquire about sexual functioning

Ask your patients about sexual concerns at every comprehensive visit. You can easily incorporate into the review of systems a general question, such as, “Do you have any sexual concerns?” If the patient does mention a sexual problem, schedule a separate visit (given appointment time constraints) to address it. History and physical examination information you gather during the comprehensive visit will be helpful in the subsequent problem-focused visit.

Taking a thorough history is key when addressing a patient’s sexual problems, since identifying possible etiologies guides treatment. Often, the cause of female sexual dysfunction is multifactorial and includes physiologic, psychologic, and relationship issues.

Explore potential causes, recommend standard therapies

Common causes of low libido in menopausal women include vasomotor symptoms, insomnia, urinary incontinence, cancer or another major medical problem, weight gain, poor body image, genitourinary syndrome of menopause (GSM) with dyspareunia, fatigue, stress, aging, relationship duration, lack of novelty, relationship conflict, and a partner’s sexual problems. Other common etiologies include depression, anxiety, and substance use disorders, as well as medications used to treat these disorders, including selective serotonin reuptake inhibitors (SSRIs).

Continue to: There are many effective therapies...

There are many effective therapies for low sexual desire to consider prior to initiating a trial of testosterone, which should be considered for HSDD only if the disorder persists after addressing all other possible contributing factors (TABLE 1).

Sex therapy, for example, provides information on sexual functioning and helps improve communication and mutual pleasure and satisfaction. Strongly encourage—if not require—a consultation with a sex therapist before prescribing testosterone for low libido. Any testosterone-derived improvement in sexual functioning will be enhanced by improved communication and additional strategies to achieve mutual pleasure.

Hormone therapy. Vasomotor symptoms, with their associated sleep disruption, fatigue, and reduced quality of life (QOL), often adversely impact sexual desire. Estrogen therapy does not appear to improve libido in otherwise asymptomatic women; however, in women with bothersome vasomotor symptoms treated with estrogen, sexual interest may increase as a result of improved sleep, fatigue, and overall QOL. The benefits of systemic hormone therapy generally outweigh its risks for most healthy women younger than age 60 who have bothersome hot flashes and night sweats.¹

Nonhormonal and other therapies. GSM with dyspareunia is a principal cause of sexual dysfunction in older women.² Many safe and effective treatments are available, including low-dose vaginal estrogen therapy, nonhormonal moisturizers and lubricants, ospemifene, vaginal dehydroepiandrosterone, and pelvic floor physical therapy.³ Urinary incontinence commonly occurs in midlife women and contributes to low libido.⁴

Lifestyle approaches. Address fatigue and stress by having the patient adjust her work and sleep schedules, obtain help with housework and meals, and engage in mind-body interventions, counseling, or yoga. Sexual function may benefit from yoga practice, likely as a result of the patient experiencing reduced stress and enhanced body image. Improving overall health and body image with regular exercise, optimal diet, and weight management may contribute to a more satisfying sex life after the onset of menopause.

Relationship refresh. Women’s sexual interest often declines with relationship duration, and both men and women who are in new relationships generally have increased libido, affirming the importance of novelty over the long term. Couples will benefit from “date nights,” weekends away from home, and trying novel positions, locations, and times for sex. Couple’s counseling may address relationship conflict.

Expert referral. Depression, anxiety, and substance use disorders are prevalent in menopausal women and contribute to sexual dysfunction. Effective therapy is available, although some pharmacologic treatments (including SSRIs) may be an additional cause of sexual dysfunction. In addition to recommending appropriate counseling and support, referring the patient to a psychopharmacologist with expertise in managing sexual adverse effects of medications may optimize care.

Continue to: Sexual function improves, but patient still wants to try testosterone

The patient returns for follow-up visits scheduled specifically to address her sexual concerns. Sex is more comfortable and pleasurable since initiating low-dose vaginal estrogen therapy. Having been on an SSRI since her mid-40s for mild depression, the patient switched to bupropion and notes improved libido and orgasmic response. She is exercising more regularly and working with a nutritionist to address a 15-lb weight gain after menopause. The couple saw a sex therapist and is communicating better about sex with more novelty in their repertoire. They are enjoying a regular date night. Although the patient’s sex life has improved with these interventions, she is still very interested in trying testosterone.

Testosterone’s effects on HSDD in menopausal women

After addressing the many factors that contribute to sexual disinterest, a trial of testosterone may be appropriate for a menopausal woman who continues to experience low libido with associated distress.

Testosterone levels decrease with aging in both men and women. Although testosterone levels decline by approximately 50% with bilateral oophorectomy, there is no decline in androgen levels with natural menopause.⁵ Testosterone circulates tightly bound to sex hormone–binding globulin (SHBG), so free or active testosterone will be reduced by oral estrogens, which increase SHBG levels.⁶ As most menopausal women will have a low testosterone level due to aging, measuring the testosterone level does not provide information about the etiology of the sexual problem.

Although some studies have identified an association between endogenous androgen levels and sexual function, the associations are modest and are of uncertain clinical significance.^7-9 Not surprisingly, other factors, such as physical and psychologic health and the quality of the relationship, often are reported as more important predictors of sexual satisfaction than androgen levels.¹⁰

While endogenous testosterone levels may not correlate with sexual function, clinical trials of carefully selected menopausal women with HSDD have shown that androgen treatment generally results in improved sexual function.¹¹ Studies demonstrate substantial improvements in sexual desire, orgasmic response, and frequency in menopausal women treated with high doses of intramuscular testosterone, which result in supraphysiologic androgen levels.^12,13 While it is interesting that women with testosterone levels in the male low range have sizeable increases in sexual desire and response, long-term use of high-dose testosterone would result in unacceptable androgenic adverse effects and risks.

Continue to: Testosterone in low doses...

Testosterone in low doses. It is more relevant to consider the impact on female sexual function of low doses of testosterone, which raise the reduced testosterone levels seen in older women to the higher levels seen in reproductive-aged women.

A series of double-blind, multicenter, randomized, placebo-controlled trials in menopausal women with HSDD examined the impact on sexual function of a transdermal testosterone patch (300 μg) that increased blood testosterone levels to the upper limit of normal for young women.^14-17 In these studies, compared with placebo, women using testosterone reported significant improvements in sexual desire, arousal, orgasmic response, frequency, and sexually related distress. Findings were consistent in surgically and naturally menopausal women, with and without the use of concurrent estrogen therapy. Improvements were clinically limited, however. On average, testosterone-treated women experienced 1 to 1.5 additional satisfying sexual events in a 4-week period compared with those treated with placebo. The percentage of women reporting a clinically meaningful benefit from treatment was significantly greater in women treated with testosterone (52%) compared with the placebo-treated women (31%).¹⁸ An appreciable placebo response was seen, typical of most studies of therapies for sexual dysfunction.

Safety concerns

Potential risks of testosterone treatment include acne, hirsutism, irreversible deepening of the voice, and adverse changes in lipids and liver function (TABLE 2).¹⁹ Adverse effects are dose dependent and are unlikely with physiologically dosed testosterone.

A 1-year study of testosterone patches in approximately 800 menopausal women with HSDD (with a subgroup of women followed for an additional year) provides the most comprehensive safety data available.¹⁷ Unwanted hair growth occurred more often in women receiving testosterone, without significant differences in blood biochemistry,hematologic parameters, carbohydrate metabolism, or lipids. Breast cancer was diagnosed in more women receiving testosterone than placebo. Although this finding may have been due to chance, the investigators concluded that long-term effects of testosterone treatment remain uncertain.

The FDA reviewed the data from the testosterone patch studies and determined that testosterone patches were effective for the treatment of HSDD in menopausal women, but more information was needed on long-term safety before approval could be granted. Another company then developed a testosterone gel product that produced similar blood levels as the testosterone patch. It was presumed that there would be similar efficacy; the principal goal of these studies was to examine long-term safety, particularly with respect to breast cancer and cardiovascular disease. Unexpectedly, although it raised testosterone blood levels to the upper limit of normal for young women, the testosterone gel product was no more effective than placebo.²⁰ The clinical trial was ended, with safety data never published.

Continue to: Availability of testosterone formulations

Currently, no androgen therapies are FDA approved for the treatment of female sexual dysfunction. Although the best evidence regarding testosterone efficacy and safety involves the use of testosterone patches (300 μg), appropriately dosed for women, these patches are not currently available. FDA-approved testosterone patches are approved for the treatment of male hypogonadism, but use of these patches in women is not recommended since they would result in very high circulating testosterone levels.

Testosterone subcutaneous implants, pellets, and intramuscular injections also are not recommended for women because of the risk of excessive dosing. Small trials of menopausal women taking oral estrogen with low sexual desire found that oral formulations of testosterone improved libido in this study population.²¹ The combination of esterified estrogens (0.625 mg) and methyltestosterone (1.25 mg) is available as a compounded, non-FDA approved product. Oral androgen formulations generally are not advised, due to potential adverse effects on lipids and liver function.²²

Compounded testosterone products. Ointments and creams may be compounded by prescription (TABLE 3). Product purity, dose, bioavailability, and quality typically are untested, and substantial variability exists between formulations and batches.²³ Applying 1% testosterone cream or gel (0.5 g/day) topically to the thigh or lower abdomen should increase the low testosterone levels typically seen in menopausal women to the higher levels seen in younger women.^24,25 Application to the vulva or vagina is not advised, as it may cause local irritation and is unpredictably absorbed.

Adapting male testosterone products. High-quality FDA-approved testosterone gel formulations are available for male hypogonadism. However, since women have approximately one-tenth the circulating testosterone levels of men, supraphysiologic dosing is a risk when these products are prescribed for women. Most testosterone products approved for men are provided in pumps or packets, and they are difficult to dose-adjust for women. Applying one-tenth the male dose of 1% testosterone gel (Testim), which comes in a resealable unit-dose tube, is an alternative to compounding. For men, the dose is 1 tube per day, so women should make 1 tube last for 10 days by using 3 to 4 drops of testosterone gel per day. Close physical contact must be avoided immediately after application, as topical hormone creams and gels are easily transferred to others. The safety and efficacy of compounded or dose-adjusted male testosterone products used in women are unknown.

Follow treated women closely. Women who elect to use transdermal testosterone therapy should be seen at 8 to 12 weeks to assess treatment response. Regular follow-up visits are required to assess response, satisfaction, and adverse effects, including acne and hirsutism. Since there may be little correlation between serum testosterone levels and the prescribed dose of a compounded testosterone product, testosterone levels should be measured regularly as a safety measure. The goal is to keep serum testosterone concentrations within the normal range for reproductive-aged women to reduce the likelihood of adverse effects. Testosterone levels should not be tested as an efficacy measure, however, as there is no testosterone level that will assure a satisfactory sex life.

CASE Conclusion

After a thorough discussion of high placebo response rates, potential adverse effects, unknown long-term risks, and off-label nature of testosterone use, the patient elects a trial of compounded 1% testosterone cream. Her clinician informs her of the limitations of compounded formulations and the need for regular testing of testosterone levels to prevent supraphysiologic dosing. At a follow-up visit 8 weeks later, she reports improved sexual desire and elects to continue treatment and monitoring. After using testosterone for 2 years, the patient is uncertain that she still is experiencing a significant benefit, stops testosterone treatment, and remains satisfied with her sex life.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Midlife woman with low libido causing distress

At her annual gynecologic visit, a 55-year-old woman notes that she has almost no interest in sex. In the past, her libido was good and relations were pleasurable. Since her mid-40s, she has noticed a gradual decline in libido and orgasmic response. Sexual frequency has declined from once or twice weekly to just a few times per month. She has been married for 25 years and describes the relationship as caring and strong. Her husband is healthy with a good libido; his intermittent erectile dysfunction is treated with a phosphodiesterase-5 inhibitor. The patient’s low libido is distressing, as the decline in sexual frequency is causing some conflict for the couple. She requests that her testosterone level be checked because she heard that treatment with testosterone cream will solve this problem.

Evaluating and treating low libido in menopausal women

Low libido is a very common sexual problem for women. When sexual problems are accompanied by distress, they are classified as sexual dysfunctions. Although ObGyns should discuss sexual concerns at every comprehensive visit, if the patient has no associated distress, treatment is not necessarily indicated. A woman with low libido or anorgasmia who is satisfied with her sex life and is not bothered by these issues does not require any intervention.

Currently, the only indication for testosterone therapy that is supported by clinical trial evidence is low sexual desire with associated distress, known as hypoactive sexual desire disorder (HSDD). Although other sexual problems also commonly occur in menopausal women, such as disorders of orgasm and pain, testosterone is not recommended for these problems. In addition, testosterone is not approved by the US Food and Drug Administration (FDA) for the treatment of female sexual dysfunction.

Routinely inquire about sexual functioning

Ask your patients about sexual concerns at every comprehensive visit. You can easily incorporate into the review of systems a general question, such as, “Do you have any sexual concerns?” If the patient does mention a sexual problem, schedule a separate visit (given appointment time constraints) to address it. History and physical examination information you gather during the comprehensive visit will be helpful in the subsequent problem-focused visit.

Taking a thorough history is key when addressing a patient’s sexual problems, since identifying possible etiologies guides treatment. Often, the cause of female sexual dysfunction is multifactorial and includes physiologic, psychologic, and relationship issues.

Explore potential causes, recommend standard therapies

Common causes of low libido in menopausal women include vasomotor symptoms, insomnia, urinary incontinence, cancer or another major medical problem, weight gain, poor body image, genitourinary syndrome of menopause (GSM) with dyspareunia, fatigue, stress, aging, relationship duration, lack of novelty, relationship conflict, and a partner’s sexual problems. Other common etiologies include depression, anxiety, and substance use disorders, as well as medications used to treat these disorders, including selective serotonin reuptake inhibitors (SSRIs).

Continue to: There are many effective therapies...

There are many effective therapies for low sexual desire to consider prior to initiating a trial of testosterone, which should be considered for HSDD only if the disorder persists after addressing all other possible contributing factors (TABLE 1).

Sex therapy, for example, provides information on sexual functioning and helps improve communication and mutual pleasure and satisfaction. Strongly encourage—if not require—a consultation with a sex therapist before prescribing testosterone for low libido. Any testosterone-derived improvement in sexual functioning will be enhanced by improved communication and additional strategies to achieve mutual pleasure.

Hormone therapy. Vasomotor symptoms, with their associated sleep disruption, fatigue, and reduced quality of life (QOL), often adversely impact sexual desire. Estrogen therapy does not appear to improve libido in otherwise asymptomatic women; however, in women with bothersome vasomotor symptoms treated with estrogen, sexual interest may increase as a result of improved sleep, fatigue, and overall QOL. The benefits of systemic hormone therapy generally outweigh its risks for most healthy women younger than age 60 who have bothersome hot flashes and night sweats.¹

Nonhormonal and other therapies. GSM with dyspareunia is a principal cause of sexual dysfunction in older women.² Many safe and effective treatments are available, including low-dose vaginal estrogen therapy, nonhormonal moisturizers and lubricants, ospemifene, vaginal dehydroepiandrosterone, and pelvic floor physical therapy.³ Urinary incontinence commonly occurs in midlife women and contributes to low libido.⁴

Lifestyle approaches. Address fatigue and stress by having the patient adjust her work and sleep schedules, obtain help with housework and meals, and engage in mind-body interventions, counseling, or yoga. Sexual function may benefit from yoga practice, likely as a result of the patient experiencing reduced stress and enhanced body image. Improving overall health and body image with regular exercise, optimal diet, and weight management may contribute to a more satisfying sex life after the onset of menopause.

Relationship refresh. Women’s sexual interest often declines with relationship duration, and both men and women who are in new relationships generally have increased libido, affirming the importance of novelty over the long term. Couples will benefit from “date nights,” weekends away from home, and trying novel positions, locations, and times for sex. Couple’s counseling may address relationship conflict.

Expert referral. Depression, anxiety, and substance use disorders are prevalent in menopausal women and contribute to sexual dysfunction. Effective therapy is available, although some pharmacologic treatments (including SSRIs) may be an additional cause of sexual dysfunction. In addition to recommending appropriate counseling and support, referring the patient to a psychopharmacologist with expertise in managing sexual adverse effects of medications may optimize care.

Continue to: Sexual function improves, but patient still wants to try testosterone

The patient returns for follow-up visits scheduled specifically to address her sexual concerns. Sex is more comfortable and pleasurable since initiating low-dose vaginal estrogen therapy. Having been on an SSRI since her mid-40s for mild depression, the patient switched to bupropion and notes improved libido and orgasmic response. She is exercising more regularly and working with a nutritionist to address a 15-lb weight gain after menopause. The couple saw a sex therapist and is communicating better about sex with more novelty in their repertoire. They are enjoying a regular date night. Although the patient’s sex life has improved with these interventions, she is still very interested in trying testosterone.

Testosterone’s effects on HSDD in menopausal women

After addressing the many factors that contribute to sexual disinterest, a trial of testosterone may be appropriate for a menopausal woman who continues to experience low libido with associated distress.

Testosterone levels decrease with aging in both men and women. Although testosterone levels decline by approximately 50% with bilateral oophorectomy, there is no decline in androgen levels with natural menopause.⁵ Testosterone circulates tightly bound to sex hormone–binding globulin (SHBG), so free or active testosterone will be reduced by oral estrogens, which increase SHBG levels.⁶ As most menopausal women will have a low testosterone level due to aging, measuring the testosterone level does not provide information about the etiology of the sexual problem.

Although some studies have identified an association between endogenous androgen levels and sexual function, the associations are modest and are of uncertain clinical significance.^7-9 Not surprisingly, other factors, such as physical and psychologic health and the quality of the relationship, often are reported as more important predictors of sexual satisfaction than androgen levels.¹⁰

While endogenous testosterone levels may not correlate with sexual function, clinical trials of carefully selected menopausal women with HSDD have shown that androgen treatment generally results in improved sexual function.¹¹ Studies demonstrate substantial improvements in sexual desire, orgasmic response, and frequency in menopausal women treated with high doses of intramuscular testosterone, which result in supraphysiologic androgen levels.^12,13 While it is interesting that women with testosterone levels in the male low range have sizeable increases in sexual desire and response, long-term use of high-dose testosterone would result in unacceptable androgenic adverse effects and risks.

Continue to: Testosterone in low doses...

Testosterone in low doses. It is more relevant to consider the impact on female sexual function of low doses of testosterone, which raise the reduced testosterone levels seen in older women to the higher levels seen in reproductive-aged women.

A series of double-blind, multicenter, randomized, placebo-controlled trials in menopausal women with HSDD examined the impact on sexual function of a transdermal testosterone patch (300 μg) that increased blood testosterone levels to the upper limit of normal for young women.^14-17 In these studies, compared with placebo, women using testosterone reported significant improvements in sexual desire, arousal, orgasmic response, frequency, and sexually related distress. Findings were consistent in surgically and naturally menopausal women, with and without the use of concurrent estrogen therapy. Improvements were clinically limited, however. On average, testosterone-treated women experienced 1 to 1.5 additional satisfying sexual events in a 4-week period compared with those treated with placebo. The percentage of women reporting a clinically meaningful benefit from treatment was significantly greater in women treated with testosterone (52%) compared with the placebo-treated women (31%).¹⁸ An appreciable placebo response was seen, typical of most studies of therapies for sexual dysfunction.

Safety concerns

Potential risks of testosterone treatment include acne, hirsutism, irreversible deepening of the voice, and adverse changes in lipids and liver function (TABLE 2).¹⁹ Adverse effects are dose dependent and are unlikely with physiologically dosed testosterone.

A 1-year study of testosterone patches in approximately 800 menopausal women with HSDD (with a subgroup of women followed for an additional year) provides the most comprehensive safety data available.¹⁷ Unwanted hair growth occurred more often in women receiving testosterone, without significant differences in blood biochemistry,hematologic parameters, carbohydrate metabolism, or lipids. Breast cancer was diagnosed in more women receiving testosterone than placebo. Although this finding may have been due to chance, the investigators concluded that long-term effects of testosterone treatment remain uncertain.

The FDA reviewed the data from the testosterone patch studies and determined that testosterone patches were effective for the treatment of HSDD in menopausal women, but more information was needed on long-term safety before approval could be granted. Another company then developed a testosterone gel product that produced similar blood levels as the testosterone patch. It was presumed that there would be similar efficacy; the principal goal of these studies was to examine long-term safety, particularly with respect to breast cancer and cardiovascular disease. Unexpectedly, although it raised testosterone blood levels to the upper limit of normal for young women, the testosterone gel product was no more effective than placebo.²⁰ The clinical trial was ended, with safety data never published.

Continue to: Availability of testosterone formulations

Currently, no androgen therapies are FDA approved for the treatment of female sexual dysfunction. Although the best evidence regarding testosterone efficacy and safety involves the use of testosterone patches (300 μg), appropriately dosed for women, these patches are not currently available. FDA-approved testosterone patches are approved for the treatment of male hypogonadism, but use of these patches in women is not recommended since they would result in very high circulating testosterone levels.

Testosterone subcutaneous implants, pellets, and intramuscular injections also are not recommended for women because of the risk of excessive dosing. Small trials of menopausal women taking oral estrogen with low sexual desire found that oral formulations of testosterone improved libido in this study population.²¹ The combination of esterified estrogens (0.625 mg) and methyltestosterone (1.25 mg) is available as a compounded, non-FDA approved product. Oral androgen formulations generally are not advised, due to potential adverse effects on lipids and liver function.²²

Compounded testosterone products. Ointments and creams may be compounded by prescription (TABLE 3). Product purity, dose, bioavailability, and quality typically are untested, and substantial variability exists between formulations and batches.²³ Applying 1% testosterone cream or gel (0.5 g/day) topically to the thigh or lower abdomen should increase the low testosterone levels typically seen in menopausal women to the higher levels seen in younger women.^24,25 Application to the vulva or vagina is not advised, as it may cause local irritation and is unpredictably absorbed.

Adapting male testosterone products. High-quality FDA-approved testosterone gel formulations are available for male hypogonadism. However, since women have approximately one-tenth the circulating testosterone levels of men, supraphysiologic dosing is a risk when these products are prescribed for women. Most testosterone products approved for men are provided in pumps or packets, and they are difficult to dose-adjust for women. Applying one-tenth the male dose of 1% testosterone gel (Testim), which comes in a resealable unit-dose tube, is an alternative to compounding. For men, the dose is 1 tube per day, so women should make 1 tube last for 10 days by using 3 to 4 drops of testosterone gel per day. Close physical contact must be avoided immediately after application, as topical hormone creams and gels are easily transferred to others. The safety and efficacy of compounded or dose-adjusted male testosterone products used in women are unknown.

Follow treated women closely. Women who elect to use transdermal testosterone therapy should be seen at 8 to 12 weeks to assess treatment response. Regular follow-up visits are required to assess response, satisfaction, and adverse effects, including acne and hirsutism. Since there may be little correlation between serum testosterone levels and the prescribed dose of a compounded testosterone product, testosterone levels should be measured regularly as a safety measure. The goal is to keep serum testosterone concentrations within the normal range for reproductive-aged women to reduce the likelihood of adverse effects. Testosterone levels should not be tested as an efficacy measure, however, as there is no testosterone level that will assure a satisfactory sex life.

CASE Conclusion

After a thorough discussion of high placebo response rates, potential adverse effects, unknown long-term risks, and off-label nature of testosterone use, the patient elects a trial of compounded 1% testosterone cream. Her clinician informs her of the limitations of compounded formulations and the need for regular testing of testosterone levels to prevent supraphysiologic dosing. At a follow-up visit 8 weeks later, she reports improved sexual desire and elects to continue treatment and monitoring. After using testosterone for 2 years, the patient is uncertain that she still is experiencing a significant benefit, stops testosterone treatment, and remains satisfied with her sex life.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Uterine fibroids are the most common solid pelvic tumor in women and a leading indication for hysterectomy in the United States.¹ As a result, they represent significant morbidity for many women and are a major public health problem. By age 50, 70% of white women and 80% of black women have fibroids.²

Although fibroids are sometimes asymptomatic, the symptoms most commonly reported are abnormal uterine bleeding (AUB) with resultant anemia and bulk/pressure symptoms. Uterine fibroids also are associated with reproductive dysfunction, such as recurrent pregnancy loss, and even infertility.³

The clinical diagnosis of uterine fibroids is made based on a combination of physical examination and imaging studies, including pelvic ultrasonography, saline infusion sonography, and magnetic resonance imaging (MRI). When medical management, such as combination oral contraceptive pills, fails in patients with AUB and/or bulk predominant symptoms or patients present with compromised fertility, the only option for conservative surgical management is a myomectomy.⁴

The route of myomectomy—hysteroscopy, laparotomy, conventional laparoscopic myomectomy (LM), or robot-assisted laparoscopic myomectomy (RALM)—depends on the size, number, location, and consistency of the uterine fibroids and, to a certain extent, the indication for the myomectomy. In some cases, multiple routes must be used to achieve optimal results, and sometimes these procedures have to be staged. In this literature review and technical summary, we focus on conventional LM and RALM approaches.

Literature review: In the right hands, LM and RALM have clear benefits

In the past, laparotomy was the surgical route of choice for fibroid removal. This surgery was associated with a long hospital stay, a high rate of blood transfusions, postoperative pain, and a lengthy recovery period. As minimally invasive surgery gained popularity, conventional LM became more commonly performed and was accepted by many as the gold standard approach for myomectomy.⁵

LM has considerable advantages over laparotomy

Compared with the traditional, more invasive route, the conventional LM approach has many benefits. These include less blood loss, decreased postoperative pain, shorter recovery time, shorter hospitalization stay, and decreased perioperative complications.⁶ LM should be considered the first-line approach unless the size of an intramural myoma exceeds 10 to 12 cm or multiple myomas (consensus, approximately 4 or more) are present and necessitate several incisions according to their varying locations within the uterus.^7,8 While this is a recommendation, reports have been published on the successful laparoscopic approach to myomas larger than 20 cm, demonstrating that a skilled, experienced surgeon can perform this procedure safely.^9-11

Many studies comparing LM with the abdominal approach showed that LM is associated with decreased blood loss, less postoperative pain, shorter hospital stay, and quicker recovery.^12-14 Unfortunately, myomectomy via conventional laparoscopy can be technically challenging, thereby limiting patient accessibility to this approach. Major challenges with conventional LM include enucleation of the fibroid along the correct plane and a multilayered hysterotomy closure.¹⁵ The obvious concern with the latter is the potential risk for uterine rupture when improperly performed as a result of deficient suturing skills. Accordingly, several cases of uterine rupture in the second and third trimester of pregnancy after LM led to recommendations for stricter selection criteria, which excluded patients with fibroids larger than 5 cm, multiple fibroids, and deep intramural fibroids.¹⁶

Continue to: The RALM approach

RALM was developed as a surgical alternative and to help overcome conventional laparoscopy challenges, such as suturing, as well as to offer minimally invasive options to a broader patient pool. In 2004, Advincula and colleagues reported the first case series of 35 women who underwent RALM.¹⁷ Since that report was published, multiple retrospective studies have confirmed RALM’s safety, feasibility, and efficacy.

How RALM stacks up against laparotomy. Compared with traditional abdominal myomectomy (AM), RALM has been associated with less blood loss, shorter hospital stay, quicker recovery time, fewer complications, and higher costs.¹⁸ In a comparative analysis of surgical outcomes and costs of RALM versus AM, Nash and colleagues found that RALM patients required less intravenous narcotics, had shorter hospital stays, and had equivalent clinical outcomes compared with AM-treated patients.¹⁹ In addition, the authors observed a correlation between increased specimen size and decreased operative efficiency with RALM. Retrospective cohort studies by Mansour and colleagues and Sangha and colleagues echoed similar conclusions.^20,21

RALM versus conventional LM. The comparisons between conventional LM and RALM are not as clear-cut, and although evidence strongly suggests a role for RALM, more comparative studies are needed.

In 2013, Pundir and colleagues completed a meta-analysis and systematic review comparing RALM with AM and LM.²² They reviewed 10 observational studies; 7 compared RALM with AM, 4 compared RALM with LM, and 1 study compared RALM with AM and LM (this was included in both groups). In the comparison between RALM and AM, estimated blood loss, blood transfusion, and length of hospital stay were significantly lower with RALM, risk of complication was similar, and operating time and costs were significantly higher. The cost findings were not too dissimilar to conclusions drawn by Advincula and colleagues in an earlier study.¹⁸

Further, when Pundir and colleagues compared RALM with LM, blood transfusion risk and costs were higher with RALM, but no significant differences were noted in estimated blood loss, operating time, length of hospital stay, and complications.²² In this analysis, RALM showed significant short-term benefits when compared with AM but no benefit when compared with LM.

Continue to: Benefits after RALM over time

Long-term benefits from RALM, such as symptom recurrence rates and fertility outcomes, have been demonstrated. In 2015, Pitter and colleagues published the first paper on symptom recurrence after RALM.²³ In this retrospective survey, 426 women underwent RALM for symptom relief or infertility across 3 practice sites; 62.9% reported being symptom free after 3 years. In addition, 80% of symptom-free women who had undergone RALM to improve fertility outcomes conceived after 3 years. The mean (SD) time to pregnancy was 7.9 (9.4) months. Overall, pregnancy rates improved and symptom recurrence increased with the interval of time since surgery.²³

In another study, Pitter and colleagues reported on pregnancy outcomes in greater detail.²⁴ They evaluated 872 women who underwent RALM between October 2005 and November 2010 at 3 centers. Of these women, 107 conceived, resulting in 127 pregnancies and 92 deliveries through 2011. The means (SD) for age at myomectomy, number of myomas removed, and myoma size were 34.8 (4.5) years, 3.9 (3.2), and 7.5 (3.0) cm (weight, 191.7 [144.8] g), respectively. Overall, the pregnancy outcomes in this study were comparable to those reported in the literature for conventional LM.

Cela and colleagues reported similar outcomes based on their review of 48 patients who underwent RALM between 2007 and 2011.²⁵ Seven women became pregnant (8 pregnancies). There were no spontaneous abortions or uterine ruptures. Following suit, Kang and colleagues reported outcomes in 100 women who underwent RALM for deep intramural fibroids (FIGO type 2 to 5).26 The average (SD) number of fibroids was 3.8 (3.5) with a mean (SD) size of 7.5 (2.1) cm. All patients recovered without major complications, and 75% of those pursuing pregnancy conceived.

The importance of LM and RALM 

After this brief review of the data on conventional LM and RALM, it is fair to conclude that both surgical options are a game changer for the minimally invasive management of uterine fibroids. Despite strong evidence that suggests laparoscopy is superior to laparotomy for myomectomy, the technical demands required for performing conventional LM may explain why it is underutilized and why the advantages of robotic surgery—with its 3-dimensional imaging and articulated instruments—make this approach an attractive alternative.

The myomectomy technique we prefer at our institution

At our medical center, we approach the majority of abdominal myomectomies via conventional LM or RALM. We carefully select candidates with the goal of ensuring a successful procedure and minimizing the risk of conversion. When selecting candidates, we consider these factors:

• size, number, location, and consistency of the fibroids
• patient’s body habitus, and
• relative size of the uterus to the length of the patient’s torso.

Additionally, any concerns raised during the preoperative workup regarding a suspected risk of occult leiomyosarcoma preclude a minimally invasive approach. Otherwise, deciding between 
conventional LM and RALM is based on surgeon preference.

Watch how it’s done

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View these surgical techniques on the multimedia channel

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Robot-assisted laparoscopic myomectomy

Arnold P. Advincula, MD, Victoria M. Fratto, MD, and Caroline Key 
A systematic approach to surgery in a 39-year-old woman with heavy menstrual bleeding who desires future fertility. Features include robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair and demonstration of the ExCITE technique for tissue extraction.

 

Laparoscopic myomectomy technique

William H. Parker, MD
A step-by-step demonstration of the laparoscopic myomectomy technique used to resect a 7-cm posterior fibroid in a 44-year-old woman.

 

 

Laparoscopic myomectomy with enclosed transvaginal tissue extraction

Ceana Nezhat, MD, and Erica Dun, MD, MPH
A surgical case of a 41-yearold woman with radiating lower abdominal pain and menorrhagia who desired removal of symptomatic myomas. Preoperative transvaginal ultrasonography revealed a 4-cm posterior pedunculated myoma and a 5-cm fundal intramural myoma.

Continue to: Preoperative MRI guides surgical approach

An MRI scan is a critical component of the patient’s preoperative evaluation. It helps to define the uterine architecture as it relates to fibroids and to rule out the presence of adenomyosis. In general, we do not offer RALM to patients who have more than 15 myomas, a single myoma that is larger than 12 to 15 cm, or when the uterus is more than 2 fingerbreadths above the umbilicus (unless the patient’s torso allows for an adequate insufflated workspace). We also try to avoid preoperative treatment with a gonadotropin–releasing hormone agonist to minimize softening of the myoma and blurring of the dissection planes.

Steps in the procedure

Once the patient is intubated, properly positioned, prepped, and draped, we turn our attention toward peritoneal entry. Factors that influence entry include the patient’s surgical history, radiologic imaging, physical examination (particularly the exam under anesthesia), and surgeon preference for optimizing access. Quite often we use a left upper quadrant entry via Palmer’s point, with subsequent port placement individualized to the patient’s pathology and abdominal topography. Three or more incisions are required to accommodate the camera and at least 2 to 3 operative instruments. Port sizes vary from 5 to 12 mm depending on the desired equipment and surgeon preference (conventional LM versus RALM [FIGURE 1]). 

A uterine manipulator is a crucial tool used when performing LM.²⁷ This instrument enables elevation of the uterus to allow for adequate visualization of the targeted myomas, traction-countertraction during enucleation, and strategic positioning during hysterotomy repair. We also use a bedside-mounted electric uterine positioning system that provides static orientation of the uterus by interfacing with the uterine manipulator, thereby obviating the need for a bedside assistant to provide that service (FIGURE 2).

Once we observe adequate myometrial blanching from the vasopressin administration, we make a strategic hysterotomy incision (preferably transverse) to allow the surgeon to more ergonomically close the defect. We then identify the pseudocapsule so that the surgeon can circumferentially enucleate the myoma and dissect it from its fibrous attachments to the surrounding myometrium.

Continue to: The energy devices used to perform the hysterotomy...

A reliable tenaculum is critical to the success of any enucleation, whether the approach is conventional LM or RALM, in order to provide adequate traction on the myoma (FIGURE 4). We try to minimize the number of hysterotomy incisions not only to reduce further blood loss, as the majority of bleeding ensues from the surrounding myometrium, but also to minimize compromise of myometrial integrity. Additionally, we take care to avoid entry into the endometrial cavity.

As we enucleate a myoma, we place it in either the anterior or posterior cul de sac. Most important, if we enucleate multiple myomas, we keep careful track of their number. We string the myomas together with suture until we extract them to ensure this. 

While hysterotomy closure can be performed with either barbed or nonbarbed sutures in a single- or a multi-layered fashion, we prefer to use a barbed suture.^29,30 Just as enucleation requires appropriate instruments, suturing requires proper needle drivers (FIGURE 5). We advise judicious use of energy to minimize thermal effects and maintain the viability of the surrounding myometrium. Once we have sutured the myometrium closed, we place an adhesion barrier. 

Although discussion of tissue extraction is beyond the scope of this Update, any surgeon embarking on either conventional LM or RALM must have a strategy for safe contained tissue extraction given the recent concerns over uncontained power morcellation.^31,32

Surgical skill and careful patient selection are key to optimal outcomes

Patients seeking conservative surgical management of their uterine fibroids should be considered candidates for either a conventional LM or RALM. Both the scientific literature and technologic advances make these approaches viable options, especially when the surgeon’s skill is appropriate and the patient’s candidacy is adequately vetted. A well thought out surgical strategy from start to finish will ensure the chances for successful completion and optimized outcomes. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Uterine fibroids are the most common solid pelvic tumor in women and a leading indication for hysterectomy in the United States.¹ As a result, they represent significant morbidity for many women and are a major public health problem. By age 50, 70% of white women and 80% of black women have fibroids.²

Although fibroids are sometimes asymptomatic, the symptoms most commonly reported are abnormal uterine bleeding (AUB) with resultant anemia and bulk/pressure symptoms. Uterine fibroids also are associated with reproductive dysfunction, such as recurrent pregnancy loss, and even infertility.³

The clinical diagnosis of uterine fibroids is made based on a combination of physical examination and imaging studies, including pelvic ultrasonography, saline infusion sonography, and magnetic resonance imaging (MRI). When medical management, such as combination oral contraceptive pills, fails in patients with AUB and/or bulk predominant symptoms or patients present with compromised fertility, the only option for conservative surgical management is a myomectomy.⁴

The route of myomectomy—hysteroscopy, laparotomy, conventional laparoscopic myomectomy (LM), or robot-assisted laparoscopic myomectomy (RALM)—depends on the size, number, location, and consistency of the uterine fibroids and, to a certain extent, the indication for the myomectomy. In some cases, multiple routes must be used to achieve optimal results, and sometimes these procedures have to be staged. In this literature review and technical summary, we focus on conventional LM and RALM approaches.

Literature review: In the right hands, LM and RALM have clear benefits

In the past, laparotomy was the surgical route of choice for fibroid removal. This surgery was associated with a long hospital stay, a high rate of blood transfusions, postoperative pain, and a lengthy recovery period. As minimally invasive surgery gained popularity, conventional LM became more commonly performed and was accepted by many as the gold standard approach for myomectomy.⁵

LM has considerable advantages over laparotomy

Compared with the traditional, more invasive route, the conventional LM approach has many benefits. These include less blood loss, decreased postoperative pain, shorter recovery time, shorter hospitalization stay, and decreased perioperative complications.⁶ LM should be considered the first-line approach unless the size of an intramural myoma exceeds 10 to 12 cm or multiple myomas (consensus, approximately 4 or more) are present and necessitate several incisions according to their varying locations within the uterus.^7,8 While this is a recommendation, reports have been published on the successful laparoscopic approach to myomas larger than 20 cm, demonstrating that a skilled, experienced surgeon can perform this procedure safely.^9-11

Many studies comparing LM with the abdominal approach showed that LM is associated with decreased blood loss, less postoperative pain, shorter hospital stay, and quicker recovery.^12-14 Unfortunately, myomectomy via conventional laparoscopy can be technically challenging, thereby limiting patient accessibility to this approach. Major challenges with conventional LM include enucleation of the fibroid along the correct plane and a multilayered hysterotomy closure.¹⁵ The obvious concern with the latter is the potential risk for uterine rupture when improperly performed as a result of deficient suturing skills. Accordingly, several cases of uterine rupture in the second and third trimester of pregnancy after LM led to recommendations for stricter selection criteria, which excluded patients with fibroids larger than 5 cm, multiple fibroids, and deep intramural fibroids.¹⁶

Continue to: The RALM approach

RALM was developed as a surgical alternative and to help overcome conventional laparoscopy challenges, such as suturing, as well as to offer minimally invasive options to a broader patient pool. In 2004, Advincula and colleagues reported the first case series of 35 women who underwent RALM.¹⁷ Since that report was published, multiple retrospective studies have confirmed RALM’s safety, feasibility, and efficacy.

How RALM stacks up against laparotomy. Compared with traditional abdominal myomectomy (AM), RALM has been associated with less blood loss, shorter hospital stay, quicker recovery time, fewer complications, and higher costs.¹⁸ In a comparative analysis of surgical outcomes and costs of RALM versus AM, Nash and colleagues found that RALM patients required less intravenous narcotics, had shorter hospital stays, and had equivalent clinical outcomes compared with AM-treated patients.¹⁹ In addition, the authors observed a correlation between increased specimen size and decreased operative efficiency with RALM. Retrospective cohort studies by Mansour and colleagues and Sangha and colleagues echoed similar conclusions.^20,21

RALM versus conventional LM. The comparisons between conventional LM and RALM are not as clear-cut, and although evidence strongly suggests a role for RALM, more comparative studies are needed.

In 2013, Pundir and colleagues completed a meta-analysis and systematic review comparing RALM with AM and LM.²² They reviewed 10 observational studies; 7 compared RALM with AM, 4 compared RALM with LM, and 1 study compared RALM with AM and LM (this was included in both groups). In the comparison between RALM and AM, estimated blood loss, blood transfusion, and length of hospital stay were significantly lower with RALM, risk of complication was similar, and operating time and costs were significantly higher. The cost findings were not too dissimilar to conclusions drawn by Advincula and colleagues in an earlier study.¹⁸

Further, when Pundir and colleagues compared RALM with LM, blood transfusion risk and costs were higher with RALM, but no significant differences were noted in estimated blood loss, operating time, length of hospital stay, and complications.²² In this analysis, RALM showed significant short-term benefits when compared with AM but no benefit when compared with LM.

Continue to: Benefits after RALM over time

Long-term benefits from RALM, such as symptom recurrence rates and fertility outcomes, have been demonstrated. In 2015, Pitter and colleagues published the first paper on symptom recurrence after RALM.²³ In this retrospective survey, 426 women underwent RALM for symptom relief or infertility across 3 practice sites; 62.9% reported being symptom free after 3 years. In addition, 80% of symptom-free women who had undergone RALM to improve fertility outcomes conceived after 3 years. The mean (SD) time to pregnancy was 7.9 (9.4) months. Overall, pregnancy rates improved and symptom recurrence increased with the interval of time since surgery.²³

In another study, Pitter and colleagues reported on pregnancy outcomes in greater detail.²⁴ They evaluated 872 women who underwent RALM between October 2005 and November 2010 at 3 centers. Of these women, 107 conceived, resulting in 127 pregnancies and 92 deliveries through 2011. The means (SD) for age at myomectomy, number of myomas removed, and myoma size were 34.8 (4.5) years, 3.9 (3.2), and 7.5 (3.0) cm (weight, 191.7 [144.8] g), respectively. Overall, the pregnancy outcomes in this study were comparable to those reported in the literature for conventional LM.

Cela and colleagues reported similar outcomes based on their review of 48 patients who underwent RALM between 2007 and 2011.²⁵ Seven women became pregnant (8 pregnancies). There were no spontaneous abortions or uterine ruptures. Following suit, Kang and colleagues reported outcomes in 100 women who underwent RALM for deep intramural fibroids (FIGO type 2 to 5).26 The average (SD) number of fibroids was 3.8 (3.5) with a mean (SD) size of 7.5 (2.1) cm. All patients recovered without major complications, and 75% of those pursuing pregnancy conceived.

The importance of LM and RALM 

After this brief review of the data on conventional LM and RALM, it is fair to conclude that both surgical options are a game changer for the minimally invasive management of uterine fibroids. Despite strong evidence that suggests laparoscopy is superior to laparotomy for myomectomy, the technical demands required for performing conventional LM may explain why it is underutilized and why the advantages of robotic surgery—with its 3-dimensional imaging and articulated instruments—make this approach an attractive alternative.

The myomectomy technique we prefer at our institution

At our medical center, we approach the majority of abdominal myomectomies via conventional LM or RALM. We carefully select candidates with the goal of ensuring a successful procedure and minimizing the risk of conversion. When selecting candidates, we consider these factors:

• size, number, location, and consistency of the fibroids
• patient’s body habitus, and
• relative size of the uterus to the length of the patient’s torso.

Additionally, any concerns raised during the preoperative workup regarding a suspected risk of occult leiomyosarcoma preclude a minimally invasive approach. Otherwise, deciding between 
conventional LM and RALM is based on surgeon preference.

Watch how it’s done

---

View these surgical techniques on the multimedia channel

---

Robot-assisted laparoscopic myomectomy

Arnold P. Advincula, MD, Victoria M. Fratto, MD, and Caroline Key 
A systematic approach to surgery in a 39-year-old woman with heavy menstrual bleeding who desires future fertility. Features include robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair and demonstration of the ExCITE technique for tissue extraction.

 

Laparoscopic myomectomy technique

William H. Parker, MD
A step-by-step demonstration of the laparoscopic myomectomy technique used to resect a 7-cm posterior fibroid in a 44-year-old woman.

 

 

Laparoscopic myomectomy with enclosed transvaginal tissue extraction

Ceana Nezhat, MD, and Erica Dun, MD, MPH
A surgical case of a 41-yearold woman with radiating lower abdominal pain and menorrhagia who desired removal of symptomatic myomas. Preoperative transvaginal ultrasonography revealed a 4-cm posterior pedunculated myoma and a 5-cm fundal intramural myoma.

Continue to: Preoperative MRI guides surgical approach

An MRI scan is a critical component of the patient’s preoperative evaluation. It helps to define the uterine architecture as it relates to fibroids and to rule out the presence of adenomyosis. In general, we do not offer RALM to patients who have more than 15 myomas, a single myoma that is larger than 12 to 15 cm, or when the uterus is more than 2 fingerbreadths above the umbilicus (unless the patient’s torso allows for an adequate insufflated workspace). We also try to avoid preoperative treatment with a gonadotropin–releasing hormone agonist to minimize softening of the myoma and blurring of the dissection planes.

Steps in the procedure

Once the patient is intubated, properly positioned, prepped, and draped, we turn our attention toward peritoneal entry. Factors that influence entry include the patient’s surgical history, radiologic imaging, physical examination (particularly the exam under anesthesia), and surgeon preference for optimizing access. Quite often we use a left upper quadrant entry via Palmer’s point, with subsequent port placement individualized to the patient’s pathology and abdominal topography. Three or more incisions are required to accommodate the camera and at least 2 to 3 operative instruments. Port sizes vary from 5 to 12 mm depending on the desired equipment and surgeon preference (conventional LM versus RALM [FIGURE 1]). 

A uterine manipulator is a crucial tool used when performing LM.²⁷ This instrument enables elevation of the uterus to allow for adequate visualization of the targeted myomas, traction-countertraction during enucleation, and strategic positioning during hysterotomy repair. We also use a bedside-mounted electric uterine positioning system that provides static orientation of the uterus by interfacing with the uterine manipulator, thereby obviating the need for a bedside assistant to provide that service (FIGURE 2).

Once we observe adequate myometrial blanching from the vasopressin administration, we make a strategic hysterotomy incision (preferably transverse) to allow the surgeon to more ergonomically close the defect. We then identify the pseudocapsule so that the surgeon can circumferentially enucleate the myoma and dissect it from its fibrous attachments to the surrounding myometrium.

Continue to: The energy devices used to perform the hysterotomy...

A reliable tenaculum is critical to the success of any enucleation, whether the approach is conventional LM or RALM, in order to provide adequate traction on the myoma (FIGURE 4). We try to minimize the number of hysterotomy incisions not only to reduce further blood loss, as the majority of bleeding ensues from the surrounding myometrium, but also to minimize compromise of myometrial integrity. Additionally, we take care to avoid entry into the endometrial cavity.

As we enucleate a myoma, we place it in either the anterior or posterior cul de sac. Most important, if we enucleate multiple myomas, we keep careful track of their number. We string the myomas together with suture until we extract them to ensure this. 

While hysterotomy closure can be performed with either barbed or nonbarbed sutures in a single- or a multi-layered fashion, we prefer to use a barbed suture.^29,30 Just as enucleation requires appropriate instruments, suturing requires proper needle drivers (FIGURE 5). We advise judicious use of energy to minimize thermal effects and maintain the viability of the surrounding myometrium. Once we have sutured the myometrium closed, we place an adhesion barrier. 

Although discussion of tissue extraction is beyond the scope of this Update, any surgeon embarking on either conventional LM or RALM must have a strategy for safe contained tissue extraction given the recent concerns over uncontained power morcellation.^31,32

Surgical skill and careful patient selection are key to optimal outcomes

Patients seeking conservative surgical management of their uterine fibroids should be considered candidates for either a conventional LM or RALM. Both the scientific literature and technologic advances make these approaches viable options, especially when the surgeon’s skill is appropriate and the patient’s candidacy is adequately vetted. A well thought out surgical strategy from start to finish will ensure the chances for successful completion and optimized outcomes. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Uterine fibroids are the most common solid pelvic tumor in women and a leading indication for hysterectomy in the United States.¹ As a result, they represent significant morbidity for many women and are a major public health problem. By age 50, 70% of white women and 80% of black women have fibroids.²

Although fibroids are sometimes asymptomatic, the symptoms most commonly reported are abnormal uterine bleeding (AUB) with resultant anemia and bulk/pressure symptoms. Uterine fibroids also are associated with reproductive dysfunction, such as recurrent pregnancy loss, and even infertility.³

The clinical diagnosis of uterine fibroids is made based on a combination of physical examination and imaging studies, including pelvic ultrasonography, saline infusion sonography, and magnetic resonance imaging (MRI). When medical management, such as combination oral contraceptive pills, fails in patients with AUB and/or bulk predominant symptoms or patients present with compromised fertility, the only option for conservative surgical management is a myomectomy.⁴

The route of myomectomy—hysteroscopy, laparotomy, conventional laparoscopic myomectomy (LM), or robot-assisted laparoscopic myomectomy (RALM)—depends on the size, number, location, and consistency of the uterine fibroids and, to a certain extent, the indication for the myomectomy. In some cases, multiple routes must be used to achieve optimal results, and sometimes these procedures have to be staged. In this literature review and technical summary, we focus on conventional LM and RALM approaches.

Literature review: In the right hands, LM and RALM have clear benefits

In the past, laparotomy was the surgical route of choice for fibroid removal. This surgery was associated with a long hospital stay, a high rate of blood transfusions, postoperative pain, and a lengthy recovery period. As minimally invasive surgery gained popularity, conventional LM became more commonly performed and was accepted by many as the gold standard approach for myomectomy.⁵

LM has considerable advantages over laparotomy

Compared with the traditional, more invasive route, the conventional LM approach has many benefits. These include less blood loss, decreased postoperative pain, shorter recovery time, shorter hospitalization stay, and decreased perioperative complications.⁶ LM should be considered the first-line approach unless the size of an intramural myoma exceeds 10 to 12 cm or multiple myomas (consensus, approximately 4 or more) are present and necessitate several incisions according to their varying locations within the uterus.^7,8 While this is a recommendation, reports have been published on the successful laparoscopic approach to myomas larger than 20 cm, demonstrating that a skilled, experienced surgeon can perform this procedure safely.^9-11

Many studies comparing LM with the abdominal approach showed that LM is associated with decreased blood loss, less postoperative pain, shorter hospital stay, and quicker recovery.^12-14 Unfortunately, myomectomy via conventional laparoscopy can be technically challenging, thereby limiting patient accessibility to this approach. Major challenges with conventional LM include enucleation of the fibroid along the correct plane and a multilayered hysterotomy closure.¹⁵ The obvious concern with the latter is the potential risk for uterine rupture when improperly performed as a result of deficient suturing skills. Accordingly, several cases of uterine rupture in the second and third trimester of pregnancy after LM led to recommendations for stricter selection criteria, which excluded patients with fibroids larger than 5 cm, multiple fibroids, and deep intramural fibroids.¹⁶

Continue to: The RALM approach

RALM was developed as a surgical alternative and to help overcome conventional laparoscopy challenges, such as suturing, as well as to offer minimally invasive options to a broader patient pool. In 2004, Advincula and colleagues reported the first case series of 35 women who underwent RALM.¹⁷ Since that report was published, multiple retrospective studies have confirmed RALM’s safety, feasibility, and efficacy.

How RALM stacks up against laparotomy. Compared with traditional abdominal myomectomy (AM), RALM has been associated with less blood loss, shorter hospital stay, quicker recovery time, fewer complications, and higher costs.¹⁸ In a comparative analysis of surgical outcomes and costs of RALM versus AM, Nash and colleagues found that RALM patients required less intravenous narcotics, had shorter hospital stays, and had equivalent clinical outcomes compared with AM-treated patients.¹⁹ In addition, the authors observed a correlation between increased specimen size and decreased operative efficiency with RALM. Retrospective cohort studies by Mansour and colleagues and Sangha and colleagues echoed similar conclusions.^20,21

RALM versus conventional LM. The comparisons between conventional LM and RALM are not as clear-cut, and although evidence strongly suggests a role for RALM, more comparative studies are needed.

In 2013, Pundir and colleagues completed a meta-analysis and systematic review comparing RALM with AM and LM.²² They reviewed 10 observational studies; 7 compared RALM with AM, 4 compared RALM with LM, and 1 study compared RALM with AM and LM (this was included in both groups). In the comparison between RALM and AM, estimated blood loss, blood transfusion, and length of hospital stay were significantly lower with RALM, risk of complication was similar, and operating time and costs were significantly higher. The cost findings were not too dissimilar to conclusions drawn by Advincula and colleagues in an earlier study.¹⁸

Further, when Pundir and colleagues compared RALM with LM, blood transfusion risk and costs were higher with RALM, but no significant differences were noted in estimated blood loss, operating time, length of hospital stay, and complications.²² In this analysis, RALM showed significant short-term benefits when compared with AM but no benefit when compared with LM.

Continue to: Benefits after RALM over time

Long-term benefits from RALM, such as symptom recurrence rates and fertility outcomes, have been demonstrated. In 2015, Pitter and colleagues published the first paper on symptom recurrence after RALM.²³ In this retrospective survey, 426 women underwent RALM for symptom relief or infertility across 3 practice sites; 62.9% reported being symptom free after 3 years. In addition, 80% of symptom-free women who had undergone RALM to improve fertility outcomes conceived after 3 years. The mean (SD) time to pregnancy was 7.9 (9.4) months. Overall, pregnancy rates improved and symptom recurrence increased with the interval of time since surgery.²³

In another study, Pitter and colleagues reported on pregnancy outcomes in greater detail.²⁴ They evaluated 872 women who underwent RALM between October 2005 and November 2010 at 3 centers. Of these women, 107 conceived, resulting in 127 pregnancies and 92 deliveries through 2011. The means (SD) for age at myomectomy, number of myomas removed, and myoma size were 34.8 (4.5) years, 3.9 (3.2), and 7.5 (3.0) cm (weight, 191.7 [144.8] g), respectively. Overall, the pregnancy outcomes in this study were comparable to those reported in the literature for conventional LM.

Cela and colleagues reported similar outcomes based on their review of 48 patients who underwent RALM between 2007 and 2011.²⁵ Seven women became pregnant (8 pregnancies). There were no spontaneous abortions or uterine ruptures. Following suit, Kang and colleagues reported outcomes in 100 women who underwent RALM for deep intramural fibroids (FIGO type 2 to 5).26 The average (SD) number of fibroids was 3.8 (3.5) with a mean (SD) size of 7.5 (2.1) cm. All patients recovered without major complications, and 75% of those pursuing pregnancy conceived.

The importance of LM and RALM 

After this brief review of the data on conventional LM and RALM, it is fair to conclude that both surgical options are a game changer for the minimally invasive management of uterine fibroids. Despite strong evidence that suggests laparoscopy is superior to laparotomy for myomectomy, the technical demands required for performing conventional LM may explain why it is underutilized and why the advantages of robotic surgery—with its 3-dimensional imaging and articulated instruments—make this approach an attractive alternative.

The myomectomy technique we prefer at our institution

At our medical center, we approach the majority of abdominal myomectomies via conventional LM or RALM. We carefully select candidates with the goal of ensuring a successful procedure and minimizing the risk of conversion. When selecting candidates, we consider these factors:

• size, number, location, and consistency of the fibroids
• patient’s body habitus, and
• relative size of the uterus to the length of the patient’s torso.

Additionally, any concerns raised during the preoperative workup regarding a suspected risk of occult leiomyosarcoma preclude a minimally invasive approach. Otherwise, deciding between 
conventional LM and RALM is based on surgeon preference.

Watch how it’s done

---

View these surgical techniques on the multimedia channel

---

Robot-assisted laparoscopic myomectomy

Arnold P. Advincula, MD, Victoria M. Fratto, MD, and Caroline Key 
A systematic approach to surgery in a 39-year-old woman with heavy menstrual bleeding who desires future fertility. Features include robot-specific techniques that facilitate fibroid enucleation and hysterotomy repair and demonstration of the ExCITE technique for tissue extraction.

 

Laparoscopic myomectomy technique

William H. Parker, MD
A step-by-step demonstration of the laparoscopic myomectomy technique used to resect a 7-cm posterior fibroid in a 44-year-old woman.

 

 

Laparoscopic myomectomy with enclosed transvaginal tissue extraction

Ceana Nezhat, MD, and Erica Dun, MD, MPH
A surgical case of a 41-yearold woman with radiating lower abdominal pain and menorrhagia who desired removal of symptomatic myomas. Preoperative transvaginal ultrasonography revealed a 4-cm posterior pedunculated myoma and a 5-cm fundal intramural myoma.

Continue to: Preoperative MRI guides surgical approach

An MRI scan is a critical component of the patient’s preoperative evaluation. It helps to define the uterine architecture as it relates to fibroids and to rule out the presence of adenomyosis. In general, we do not offer RALM to patients who have more than 15 myomas, a single myoma that is larger than 12 to 15 cm, or when the uterus is more than 2 fingerbreadths above the umbilicus (unless the patient’s torso allows for an adequate insufflated workspace). We also try to avoid preoperative treatment with a gonadotropin–releasing hormone agonist to minimize softening of the myoma and blurring of the dissection planes.

Steps in the procedure

Once the patient is intubated, properly positioned, prepped, and draped, we turn our attention toward peritoneal entry. Factors that influence entry include the patient’s surgical history, radiologic imaging, physical examination (particularly the exam under anesthesia), and surgeon preference for optimizing access. Quite often we use a left upper quadrant entry via Palmer’s point, with subsequent port placement individualized to the patient’s pathology and abdominal topography. Three or more incisions are required to accommodate the camera and at least 2 to 3 operative instruments. Port sizes vary from 5 to 12 mm depending on the desired equipment and surgeon preference (conventional LM versus RALM [FIGURE 1]). 

A uterine manipulator is a crucial tool used when performing LM.²⁷ This instrument enables elevation of the uterus to allow for adequate visualization of the targeted myomas, traction-countertraction during enucleation, and strategic positioning during hysterotomy repair. We also use a bedside-mounted electric uterine positioning system that provides static orientation of the uterus by interfacing with the uterine manipulator, thereby obviating the need for a bedside assistant to provide that service (FIGURE 2).

Once we observe adequate myometrial blanching from the vasopressin administration, we make a strategic hysterotomy incision (preferably transverse) to allow the surgeon to more ergonomically close the defect. We then identify the pseudocapsule so that the surgeon can circumferentially enucleate the myoma and dissect it from its fibrous attachments to the surrounding myometrium.

Continue to: The energy devices used to perform the hysterotomy...

A reliable tenaculum is critical to the success of any enucleation, whether the approach is conventional LM or RALM, in order to provide adequate traction on the myoma (FIGURE 4). We try to minimize the number of hysterotomy incisions not only to reduce further blood loss, as the majority of bleeding ensues from the surrounding myometrium, but also to minimize compromise of myometrial integrity. Additionally, we take care to avoid entry into the endometrial cavity.

As we enucleate a myoma, we place it in either the anterior or posterior cul de sac. Most important, if we enucleate multiple myomas, we keep careful track of their number. We string the myomas together with suture until we extract them to ensure this. 

While hysterotomy closure can be performed with either barbed or nonbarbed sutures in a single- or a multi-layered fashion, we prefer to use a barbed suture.^29,30 Just as enucleation requires appropriate instruments, suturing requires proper needle drivers (FIGURE 5). We advise judicious use of energy to minimize thermal effects and maintain the viability of the surrounding myometrium. Once we have sutured the myometrium closed, we place an adhesion barrier. 

Although discussion of tissue extraction is beyond the scope of this Update, any surgeon embarking on either conventional LM or RALM must have a strategy for safe contained tissue extraction given the recent concerns over uncontained power morcellation.^31,32

Surgical skill and careful patient selection are key to optimal outcomes

Patients seeking conservative surgical management of their uterine fibroids should be considered candidates for either a conventional LM or RALM. Both the scientific literature and technologic advances make these approaches viable options, especially when the surgeon’s skill is appropriate and the patient’s candidacy is adequately vetted. A well thought out surgical strategy from start to finish will ensure the chances for successful completion and optimized outcomes. 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The most useful applications (apps) for health care professionals and students? Medical calculator apps (along with drug reference and disease diagnosis apps), according to surveys of clinicians and students.^1,2 The utility of calculator apps to these groups is not surprising; calculator apps fall in the category of clinical decision-making apps, which also includes decision support systems, clinical treatment guidelines, disease diagnosis aids, differential diagnosis aids, laboratory test ordering, laboratory test interpretation, and medical exams.³ Calculator apps obviously save time as most health care providers have not memorized the many medical formulas and do not have computational speed. I have previously discussed other, more ObGyn-specific calculators, such as due date calculators.^4,5 In this App Review column, however, I would like to highlight 3 general calculator apps: Calculate by QxMD, CliniCalc Medical Calculator, and Medscape. Researchers found all 3 apps 100% accurate and contained the most functions desired by internists.⁶ The apps are available at no cost and include many unique calculators. My colleagues and I actually used Calculate by QxMD to verify calculations in a previous study.⁷

A clinical example for how to apply calculators in practice is as follows: A multiparous patient at term has undergone an unscheduled cesarean delivery for arrest of dilation and intra-amniotic infection. You need to decide if the patient requires anti‑coagulants for deep venous thrombosis (DVT) prophylaxis and her necessary daily dose for gentamicin for postpartum infection prophylaxis. You can use Medscape’s body mass index (BMI) calculator to find out that this patient’s BMI is 45 kg/m² and that DVT prophylaxis is in fact indicated. You also can use QxMD’s ideal body weight calculator to get the patient’s weight and determine the appropriate daily dose for gentamicin.

The TABLE provides more information on the apps, with its inclusions based on a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature used, and important special features).⁷

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The most useful applications (apps) for health care professionals and students? Medical calculator apps (along with drug reference and disease diagnosis apps), according to surveys of clinicians and students.^1,2 The utility of calculator apps to these groups is not surprising; calculator apps fall in the category of clinical decision-making apps, which also includes decision support systems, clinical treatment guidelines, disease diagnosis aids, differential diagnosis aids, laboratory test ordering, laboratory test interpretation, and medical exams.³ Calculator apps obviously save time as most health care providers have not memorized the many medical formulas and do not have computational speed. I have previously discussed other, more ObGyn-specific calculators, such as due date calculators.^4,5 In this App Review column, however, I would like to highlight 3 general calculator apps: Calculate by QxMD, CliniCalc Medical Calculator, and Medscape. Researchers found all 3 apps 100% accurate and contained the most functions desired by internists.⁶ The apps are available at no cost and include many unique calculators. My colleagues and I actually used Calculate by QxMD to verify calculations in a previous study.⁷

A clinical example for how to apply calculators in practice is as follows: A multiparous patient at term has undergone an unscheduled cesarean delivery for arrest of dilation and intra-amniotic infection. You need to decide if the patient requires anti‑coagulants for deep venous thrombosis (DVT) prophylaxis and her necessary daily dose for gentamicin for postpartum infection prophylaxis. You can use Medscape’s body mass index (BMI) calculator to find out that this patient’s BMI is 45 kg/m² and that DVT prophylaxis is in fact indicated. You also can use QxMD’s ideal body weight calculator to get the patient’s weight and determine the appropriate daily dose for gentamicin.

The TABLE provides more information on the apps, with its inclusions based on a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature used, and important special features).⁷

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The most useful applications (apps) for health care professionals and students? Medical calculator apps (along with drug reference and disease diagnosis apps), according to surveys of clinicians and students.^1,2 The utility of calculator apps to these groups is not surprising; calculator apps fall in the category of clinical decision-making apps, which also includes decision support systems, clinical treatment guidelines, disease diagnosis aids, differential diagnosis aids, laboratory test ordering, laboratory test interpretation, and medical exams.³ Calculator apps obviously save time as most health care providers have not memorized the many medical formulas and do not have computational speed. I have previously discussed other, more ObGyn-specific calculators, such as due date calculators.^4,5 In this App Review column, however, I would like to highlight 3 general calculator apps: Calculate by QxMD, CliniCalc Medical Calculator, and Medscape. Researchers found all 3 apps 100% accurate and contained the most functions desired by internists.⁶ The apps are available at no cost and include many unique calculators. My colleagues and I actually used Calculate by QxMD to verify calculations in a previous study.⁷

A clinical example for how to apply calculators in practice is as follows: A multiparous patient at term has undergone an unscheduled cesarean delivery for arrest of dilation and intra-amniotic infection. You need to decide if the patient requires anti‑coagulants for deep venous thrombosis (DVT) prophylaxis and her necessary daily dose for gentamicin for postpartum infection prophylaxis. You can use Medscape’s body mass index (BMI) calculator to find out that this patient’s BMI is 45 kg/m² and that DVT prophylaxis is in fact indicated. You also can use QxMD’s ideal body weight calculator to get the patient’s weight and determine the appropriate daily dose for gentamicin.

The TABLE provides more information on the apps, with its inclusions based on a shortened version of the APPLICATIONS scoring system, APPLI (app comprehensiveness, price, platform, literature used, and important special features).⁷

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Your patient wants ovarian reserve testing. Is her request reasonable?

A 34-year-old woman, recently married, plans to delay attempting pregnancy for a few years. She requests ovarian reserve testing to inform this timeline.

This is not an unreasonable inquiry, given her age (<35 years), after which there is natural acceleration in the rate of decline in the quality of oocytes. Regardless of the results of testing, attempting pregnancy or pursuing fertility preservation as soon as possible (particularly in patients >35 years) is associated with better outcomes.

A woman is born with all the eggs she will ever have. Oocyte atresia occurs throughout a woman’s lifetime, from 1,000,000 eggs at birth to only 1,000 by the time of menopause.¹ A woman’s ovarian reserve reflects the number of oocytes present in the ovaries and is the result of complex interactions of age, genetics, and environmental variables.

Ovarian reserve testing, however, only has been consistently shown to predict ovarian response to stimulation with gonadotropins; these tests might reflect in vitro fertilization (IVF) birth outcomes to a lesser degree, but have not been shown to predict natural fecundability.^2,3 Essentially, ovarian reserve testing provides a partial view of reproductive potential.

Ovarian reserve testing also does not reflect an age-related decline in oocyte quality, particularly after age 35.^4,5 As such, female age is the principal driver of fertility potential, regardless of oocyte number. A woman with abnormal ovarian reserve tests may benefit from referral to a fertility specialist for counseling that integrates her results, age, and medical history, with the caveat that abnormal results do not necessarily mean she needs assisted reproductive technology (ART) to conceive.

In this article, we review 6 common questions about the ovarian reserve, providing current data to support the answers.

Continue to: #1 What tests are part of an ovarian reserve assessment?

#1 What tests are part of an ovarian reserve assessment? What is their utility?

FSH and estradiol

Follicle-stimulating hormone (FSH) and estradiol should be checked together in the early follicular phase (days 2 to 4 of the cycle). Elevated levels of one or both hormones suggest diminished ovarian reserve; an FSH level greater than 10 mIU/mL and/or an estradiol level greater than 80 pg/mL represent abnormal results⁶ (TABLE 1). Because FSH demonstrates significant intercycle variability, a single abnormal result should be confirmed in a subsequent cycle.⁷

In addition to high intercycle variability, an FSH level is reliable only in the setting of normal hypothalamic and pituitary function.⁷ Conditions such a prolactinoma (or other causes of hyperprolactinemia), other intracranial masses, prior central radiation, hormone-based medication use, and inadequate energy reserve (as the result of anorexia nervosa, resulting in hypothalamic suppression), might result in a low or inappropriately normal FSH level that does not reflect ovarian function.¹¹

Antral follicle count

Antral follicle count (AFC) is defined as the total number of follicles measuring 2 to 10 mm, in both ovaries, in the early follicular phase (days 2 to 4 of the cycle). A count of fewer than 6 to 10 antral follicles in total is considered consistent with diminished ovarian reserve^6,12,13 (TABLE 1). Antral follicle count is not predictive of natural fecundity but, rather, projects ovarian response during IVF. Antral follicle count has been shown to decrease by 5% a year with increasing age among women with or without infertility.¹⁴

Studies have highlighted concerns regarding interobserver and intraobserver variability in determining the AFC but, in experienced hands, the AFC is a reliable test of ovarian reserve.^15,16 Visualization of antral follicles can be compromised in obese patients.¹¹ Conversely, AFC sometimes also overestimates ovarian reserve, because atretic follicles might be included in the count.^11,15 Last, AFC is reduced in patients who take a hormone-based medication but recovers with cessation of the medication.¹⁷ Ideally, a woman should stop all hormone-based medications for 2 or 3 months (≥2 or 3 spontaneous cycles) before AFC is measured.

Continue to: Anti-Müllerian hormone

A transforming growth factor β superfamily peptide produced by preantral and early antral follicles of the ovary, anti-Müllerian hormone (AMH) is a direct and quantitative marker of ovarian reserve.¹⁸ AMH is detectable at birth; the level rises slowly until puberty, reaching a peak at approximately 16 years of age,¹⁹ then remains relatively stable until 25 years, after which AMH and age are inversely correlated, reflecting ongoing oocyte atresia. AMH declines roughly 5% a year with increasing age.¹⁴

A low level of AMH (<1 ng/mL) suggests diminished ovarian reserve^20,21 (TABLE 1). AMH has been consistently validated only for predicting ovarian response during IVF.^2,20 To a lesser extent, AMH might reflect the likelihood of pregnancy following ART, although studies are inconsistent on this point.²² AMH is not predictive of natural fecundity or time to spontaneous conception.^3,23 Among 700 women younger than age 40, AMH levels were not significantly different among those with or without infertility, and a similar percentage of women in both groups had what was characterized as a “very low” AMH level (<0.7 ng/mL).¹⁴

At the other extreme, a high AMH value (>3.5 ng/mL) predicts a hyper-response to ovarian stimulation with gonadotropins and elevated risk of ovarian hyperstimulation syndrome. In conjunction with clinical and other laboratory findings, an elevated level of AMH also can suggest polycystic ovary syndrome. No AMH cutoff for a diagnosis of polycystic ovary syndrome exists, although a level of greater than 5 to 7.8 ng/mL has been proposed as a point of delineation.^24,25

Unlike FSH and AFC, AMH is generally considered to be a valid marker of ovarian reserve throughout the menstrual cycle. AMH levels are higher in the follicular phase of the cycle and lower in the midluteal phase, but the differences are minor and seldom alter the patient’s overall prognosis.^26-29 As with FSH and AFC, levels of AMH are significantly lower in patients who are pregnant or taking hormone-based medications: Hormonal contraception lowers AMH level by 30% to 50%.^17,30,31 Ideally, patients should stop all hormone-based medications for 2 or 3 months (≥2 or 3 spontaneous cycles) before testing ovarian reserve.

#2 Who should have ovarian reserve testing?

The clinical criteria and specific indications for proceeding with ovarian reserve testing are summarized in TABLE 2.^13,32-34 Such testing is not indicated in women who are planning to attempt pregnancy but who do not have risk factors for diminished ovarian reserve. These tests cannot predict their success at becoming pregnant; age is a far more appropriate predictor of pregnancy and risk of miscarriage.³ At most, an abnormal result in a patient who meets one of the clinical criteria for testing could prompt earlier referral to a reproductive specialist for consultation—after it is explained to her that abnormal ovarian reserve tests do not, alone, mean that ART is required.

Continue to: #3 Can I reassure my patient about her reproductive potential using these tests?

Normal findings on ovarian reserve testing suggests that a woman might have a normal (that is, commensurate with age-matched peers) number of eggs in her ovaries. But normal test results do not mean she will have an easy time conceiving. Similarly, abnormal results do not mean that she will have difficulty conceiving.

Ovarian reserve testing reflects only the number of oocytes, not their quality, which is primarily determined by maternal age.³⁵ Genetic testing of embryos during IVF shows that the percentage of embryos that are aneuploid (usually resulting from abnormal eggs) rises with advancing maternal age, beginning at 35 years.⁵ The increasing rate of oocyte aneuploidy is also reflected in the rising rate of loss of clinically recognized pregnancies with advancing maternal age: from 11% in women younger than age 34 to greater than 36% in women older than age 42.⁴

Furthermore, ovarian reserve testing does not reflect other potential genetic barriers to reproduction, such as a chromosomal translocation that can result in recurrent pregnancy loss. Fallopian tube obstruction and uterine issues, such as fibroids or septa, and male factors are also not reflected in ovarian reserve testing.

#4 My patient is trying to get pregnant and has abnormal ovarian reserve testing results. Will she need IVF?"

Not necessarily. Consultation with a fertility specialist to discuss the nuances of abnormal test results and management options is ideal but, essentially, as the American Society for Reproductive Medicine states, “evidence of [diminished ovarian reserve] does not necessarily equate with inability to conceive.” Furthermore, the Society states, “there is insufficient evidence to recommend that any ovarian reserve test now available should be used as a sole criterion for the use of ART.”

Once counseled, patients might elect to pursue more aggressive treatment, but they might not necessarily need it. Age must figure significantly into treatment decisions, because oocyte quality—regardless of number—begins to decline at 35 years of age, with an associated increasing risk of infertility and miscarriage.

In a recently published study of 750 women attempting pregnancy, women with a low AMH level (<0.7 ng/mL) or high FSH level (>10 mIU/mL), or both, did not have a significantly lower likelihood of achieving spontaneous pregnancy within 1 year, compared with women with normal results of ovarian reserve testing.³

Continue to: #5 My patient is not ready to be pregnant

#5 My patient is not ready to be pregnant. If her results are abnormal, should she freeze eggs?

For patients who might be interested in seeking fertility preservation and ART, earlier referral to a reproductive specialist to discuss risks and benefits of oocyte or embryo cryopreservation is always preferable. The younger a woman is when she undergoes fertility preservation, the better. Among patients planning to delay conception, each one’s decision is driven by her personal calculations of the cost, risk, and benefit of egg or embryo freezing—a picture of which ovarian reserve testing is only one piece.

#6 Can these tests predict menopause?

Menopause is a clinical diagnosis, defined as 12 months without menses (without hormone use or other causes of amenorrhea). In such women, FSH levels are elevated, but biochemical tests are not part of the menopause diagnosis.³⁶ In the years leading to menopause, FSH levels are highly variable and unreliable in predicting time to menopause.

AMH has been shown to correlate with time to menopause. (Once the AMH level becomes undetectable, menopause occurs in a mean of 6 years.^37,38) Patients do not typically have serial AMH measurements, however, so it is not usually known when the hormone became undetectable. Therefore, AMH is not a useful test for predicting time to menopause.

Premature ovarian insufficiency (loss of ovarian function in women younger than age 40), should be considered in women with secondary amenorrhea of 4 months or longer. The diagnosis requires confirmatory laboratory assessment,³⁶ and findings include an FSH level greater than 25 mIU/mL on 2 tests performed at least 1 month apart.^39,40

Ovarian reserve tests: A partial view of reproductive potential

The answers we have provided highlight several key concepts and conclusions that should guide clinical practice and decisions made by patients:

1. Ovarian reserve tests best serve to predict ovarian response during IVF; to a far lesser extent, they might predict birth outcomes from IVF. These tests have not, however, been shown to predict spontaneous pregnancy.
2. Ovarian reserve tests should be administered purposefully, with counseling beforehand regarding their limitations.
3. Abnormal ovarian reserve test results do not necessitate ART; however, they may prompt a patient to accelerate her reproductive timeline and consult with a reproductive endocrinologist to consider her age and health-related risks of infertility or pregnancy loss.
4. Patients should be counseled that, regardless of the results of ovarian reserve testing, attempting conception or pursuing fertility preservation at a younger age (in particular, at <35 years of age) is associated with better outcomes.

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CASE Your patient wants ovarian reserve testing. Is her request reasonable?

A 34-year-old woman, recently married, plans to delay attempting pregnancy for a few years. She requests ovarian reserve testing to inform this timeline.

This is not an unreasonable inquiry, given her age (<35 years), after which there is natural acceleration in the rate of decline in the quality of oocytes. Regardless of the results of testing, attempting pregnancy or pursuing fertility preservation as soon as possible (particularly in patients >35 years) is associated with better outcomes.

A woman is born with all the eggs she will ever have. Oocyte atresia occurs throughout a woman’s lifetime, from 1,000,000 eggs at birth to only 1,000 by the time of menopause.¹ A woman’s ovarian reserve reflects the number of oocytes present in the ovaries and is the result of complex interactions of age, genetics, and environmental variables.

Ovarian reserve testing, however, only has been consistently shown to predict ovarian response to stimulation with gonadotropins; these tests might reflect in vitro fertilization (IVF) birth outcomes to a lesser degree, but have not been shown to predict natural fecundability.^2,3 Essentially, ovarian reserve testing provides a partial view of reproductive potential.

Ovarian reserve testing also does not reflect an age-related decline in oocyte quality, particularly after age 35.^4,5 As such, female age is the principal driver of fertility potential, regardless of oocyte number. A woman with abnormal ovarian reserve tests may benefit from referral to a fertility specialist for counseling that integrates her results, age, and medical history, with the caveat that abnormal results do not necessarily mean she needs assisted reproductive technology (ART) to conceive.

In this article, we review 6 common questions about the ovarian reserve, providing current data to support the answers.

Continue to: #1 What tests are part of an ovarian reserve assessment?

#1 What tests are part of an ovarian reserve assessment? What is their utility?

FSH and estradiol

Follicle-stimulating hormone (FSH) and estradiol should be checked together in the early follicular phase (days 2 to 4 of the cycle). Elevated levels of one or both hormones suggest diminished ovarian reserve; an FSH level greater than 10 mIU/mL and/or an estradiol level greater than 80 pg/mL represent abnormal results⁶ (TABLE 1). Because FSH demonstrates significant intercycle variability, a single abnormal result should be confirmed in a subsequent cycle.⁷