C.-N. Kao

Phenotypic comparison of Caucasian and Asian women with polycystic ovary syndrome: a cross-sectional study

OBJECTIVE To determine whether manifestations of polycystic ovary syndrome (PCOS), particularly androgen excess, differ between Caucasian and Asian women in the San Francisco Bay Area. DESIGN Cross-sectional study. SETTING Multidisciplinary PCOS clinic at a tertiary academic center. PATIENT(S) 121 Caucasian and 28 Asian women, aged 18-44, examined between 2006 and 2011 with PCOS verified by a reproductive endocrinologist and dermatologist according to the Rotterdam criteria. INTERVENTION(S) Transvaginal ultrasounds, comprehensive dermatologic exams, and serum testing. MAIN OUTCOME MEASURE(S) Hirsutism defined as a modified Ferriman-Gallwey (mFG) score ≥ 8, acne, androgenic alopecia, and biochemical hyperandrogenism. RESULT(S) Caucasian and Asian women had a similar prevalence of all measures of androgen excess. Both groups had similar total mFG scores and site-specific mFG scores, except Asian women had a lower site-specific mFG score for the chest. Although Asian women were more likely to use laser hair removal, the results were unchanged when the women with a history of laser hair removal were excluded. CONCLUSION(S) Caucasian and Asian women with PCOS living in the same geographic region had a similar prevalence of hirsutism as well as other markers for androgen excess. Further studies are necessary to evaluate the need for ethnic-specific mFG scores in women with PCOS.

Impact of pituitary suppression on antral follicle count and oocyte recovery after ovarian stimulation

OBJECTIVE To investigate the potential influence of short-term pituitary suppression on antral follicle count (AFC) and correlate the AFC with the number of oocytes retrieved after ovarian stimulation. DESIGN Retrospective study. SETTING University fertility center. PATIENT(S) A total of 1,479 infertile patients. INTERVENTION(S) Patients had baseline AFC, when they were not on any medications known to cause pituitary suppression, and follow-up AFC (suppressed AFC) while on E2, GnRH agonist (GnRH-a), oral contraceptive (OC) pills, or OC pills/GnRH-a in preparation for ovarian stimulation, performed within 6 months of initial baseline AFC. MAIN OUTCOME MEASURE(S) The AFC at baseline, AFC during pituitary suppression, and the number of oocytes retrieved. RESULT(S) Although there was an average unadjusted decline of 0.4, 0.9, 2.2, and 3.0 in AFC while patients were on E2, GnRH-a, OC pills, and OC pills/GnRH-a, respectively, this decline was driven by age, baseline AFC, and the hormones used. Although baseline and suppressed AFC were found to be good predictors of the number of oocytes retrieved after ovarian stimulation, statistically, suppressed AFC was found to be a marginally better predictor. CONCLUSION(S) Short-term pituitary suppression has a negative impact on AFC. This decline in AFC may influence the number of oocytes retrieved, suggesting the suppressive impact of exogenous hormones on the biological capacity of the ovary during stimulation.

Raising threshold for diagnosis of polycystic ovary syndrome excludes population of patients with metabolic risk

OBJECTIVE To characterize the population of patients excluded from a diagnosis of polycystic ovary syndrome (PCOS) when follicle number criteria are increased to 25 per ovary as suggested by the Androgen Excess and Polycystic Ovary Syndrome Societys recent task force. DESIGN Cross-sectional study. SETTING Tertiary academic center. PATIENT(S) A total of 259 women with PCOS according to Rotterdam criteria who were systematically examined from 2007 to 2015, with 1,100 ovulatory women participating in the Ovarian Aging (OVA) Study as controls. INTERVENTION(S) Anthropometric measurements, serum testing, ultrasonic imaging, and comprehensive dermatologic exams. MAIN OUTCOME MEASURE(S) Body mass index (BMI), waist to hip ratio (WHR), serum cholesterol, fasting glucose and insulin, follicle count per ovary, biochemical hyperandrogenemia, and hirsutism. RESULT(S) Forty-seven of 259 women meeting the Rotterdam criteria (18.1%) were excluded from a diagnosis of PCOS when the follicle number criteria was increased to 25. These women had clinical evidence of hyperandrogenism (68.1%) and biochemical hyperandrogenemia (44.7%), although fewer reported oligoanovulation (26.8%). The excluded women had elevated total cholesterol, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR) when compared with controls despite controlling for age and BMI. CONCLUSION(S) The women excluded from the PCOS diagnosis by raising the threshold of follicle number per ovary to ≥25 continue to show evidence of metabolic risk.

Antimüllerian hormone levels and antral follicle counts are not reduced compared with community controls in patients with rigorously defined unexplained infertility

OBJECTIVE To test the hypothesis that women with unexplained infertility demonstrate evidence of diminished ovarian reserve when compared with a population of community controls. DESIGN Cross-sectional study. SETTING Multicenter university-based clinical practices. PATIENT(S) Study participants included 277 healthy, normo-ovulatory female partners with rigorously defined unexplained infertility randomly selected from a multicenter trial (Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation). Controls included 226 healthy, normo-ovulatory women not seeking treatment for fertility from a community-based cohort (Ovarian Aging study). INTERVENTION(S) Serum antimüllerian hormone (AMH) assay at a central laboratory, FSH, fasting serum metabolic testing, transvaginal ultrasonography for antral follicle counts (AFCs), anthropometric measurements. MAIN OUTCOME MEASURE(S) Average AMH, AFC, and AMH/AFC were compared between infertile and control women by age. Analyses of covariance compared these outcomes while controlling for confounders, including age, race, body mass index, smoking history, and study site. RESULT(S) In our models, AMH, AFC, and AMH/AFC ovarian reserve indices did not differ between infertile women and community-based controls, after controlling for age, race, body mass index, smoking history, and study site. CONCLUSION(S) Currently utilized predictors of ovarian reserve do not discriminate women with rigorously defined unexplained infertility from healthy community-based women of similar demographic characteristics. Contrary to our hypothesis, among women with FSH in the normal range (≤12 IU/L), women with unexplained infertility did not show evidence of decreased ovarian reserve as measured by AMH and AFC. Ovarian reserve markers in isolation may not serve as predictors of future fertility.

Age‐stratified thresholds of anti‐Müllerian hormone improve prediction of polycystic ovary syndrome over a population‐based threshold

Due to its consistent elevation in polycystic ovary syndrome (PCOS) and correlation with polycystic ovarian morphology (PCOM), anti‐Mullerian hormone (AMH) has been proposed as a marker of the syndrome. However, prior studies reporting thresholds of AMH for a PCOS diagnosis have been limited by small sample size, inappropriate controls, and heterogeneous AMH assays. We sought to evaluate the suitability of a standardized AMH assay as a biomarker of PCOS.

Birth weight and childhood growth in daughters of women with irregular menstrual cycles

Abstract Menstrual irregularity has been associated with insulin resistance, type 2 diabetes mellitus and markers of metabolic dysfunction. This study aimed to determine whether irregular menstrual cycles (MCs) in reproductive-age women are associated with the weight of their daughters at birth and growth up to age five. We studied 4863 pregnant women with menstrual history data in a prospective cohort, recruited from the Kaiser Health Plan (1959–1966). Serial measures of their daughters’ weight and height were abstracted from medical records. We used analysis of covariance, stratified by maternal body mass index, to explore the association between maternal MC and infant birth weight (BW). We included 4774 daughters in a repeated measures analysis to compare the effect of maternal MC on childhood weight through age five. Daughters of non-obese women with irregular MC had a statistically significant lower BW compared to daughters of women with regular MC; this difference was notably amplified among obese women. The daughters’ weights were not statistically different when growth was assessed from birth to five years. We conclude that daughters of obese women with irregular MC, in particular, had significantly lower BW compared to daughters of women with regular MC, which did not persist over five years of follow-up.

Impact of the levonorgestrel-releasing intrauterine device on controlled ovarian stimulation outcomes

OBJECTIVE To report differences in ovarian stimulation outcomes in women using a levonorgestrel-releasing intrauterine device (LNG-IUD). DESIGN Retrospective cohort study. SETTING University-based infertility practice. PATIENT(S) Female patients pursuing either social oocyte cryopreservation or oocyte donation. INTERVENTION(S) Chart review of all female patients presenting from January 1, 2012, to June 30, 2017, for social oocyte cryopreservation or oocyte donation. Demographic data, cycle performance data, and the presence or absence of an LNG-IUD at the time of ovarian stimulation were compared. MAIN OUTCOME MEASURE(S) Total oocyte yield and total mature oocyte yield. Secondary measures included clinical pregnancy rate and live birth rate in recipients of donor oocytes. RESULT(S) Univariate analysis of predicted oocyte yield and mature oocyte yield showed no significant difference between subjects with and without an LNG. When controlling for history of recent hormonal contraceptive use, initial antral follicle count (AFC), age, body mass index (BMI), gonadotropin dose, and stimulation day/protocol, no significant differences were seen in total oocyte yield or mature oocyte yield in the presence or absence of an LNG-IUD. Univariate analysis of the effect of LNG-IUDs on the predicted clinical pregnancy rate and live birth rate did not significantly differ for oocyte recipients. Controlling for history of recent hormonal contraceptive use, initial AFC, age, BMI, gonadotropin dose, and stimulation day/protocol also showed no significant differences in the predicted clinical pregnancy rate and live birth rate. CONCLUSION(S) LNG-IUDs do not affect cycle performance in women undergoing ovarian stimulation cycles.

Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study

OBJECTIVE To estimate rates of ovarian aging in polycystic ovary syndrome (PCOS) subjects versus a community control population. DESIGN Longitudinal. SETTING Tertiary academic center. SUBJECT(S) PCOS subjects diagnosed according to the 2004 Rotterdam criteria were systematically enrolled in a PCOS cohort study. The comparison control subjects were from the Ovarian Aging study, a prospective longitudinal study of ovarian aging in healthy women with regular menstrual cycles. INTERVENTION(S) Clinical data collection over two study visits. MAIN OUTCOME MEASURE(S) Antral follicle count (AFC), ovarian volume (OV), and antimüllerian hormone level (AMH). RESULT(S) PCOS subjects were found to have higher baseline values for all ovarian reserve markers compared with control subjects. Univariate models indicated that, compared with control subjects, PCOS patients experienced significantly faster rates of decline for both AFC and AMH. Change in OV did not differ significantly. To account for potential confounder effects, multiple analysis of covariance models were evaluated for the best fit, considering age, body mass index, and baseline ovarian reserve markers. Adjusted models demonstrated that PCOS patients do not experience a significant difference in AFC decline compared with control subjects, but they do experience a faster rate of decline in AMH (P<.01) and slower rate of decline in OV (P<.01). CONCLUSION(S) Ovarian aging in PCOS is characterized by a more rapid decline in AMH and a slower decline in OV compared with control subjects.

SEMEN PARAMETERS AMONGST TRANSGENDER WOMEN WITH A HISTORY OF HORMONAL TREATMENT

OBJECTIVE To report on the semen quality parameters in transgender women who pursued semen cryopreservation either in the presence or absence of gender-affirming hormonal medication. MATERIALS AND METHODS This retrospective cohort study was conducted as a chart review of consecutive transgender women presenting for semen cryopreservation between January 1, 2012 and March 31, 2018. Demographic data and semen parameters were assessed. Primary outcomes were the semen parameters in subjects with either no exposure, previous exposure or current exposure to gender-affirming hormonal medication. RESULTS Twenty-eight patients presented for semen cryopreservation and produced 69 specimens. Using a Kruskal-Wallis test, semen analyses were compared between patients who had never used gender-affirming hormonal medication, those who had previously used hormonal medication but discontinued prior to specimen collection, and those who used medication at the time of specimen collection. Median semen parameters for each group were as follows: volume-2.7 mL, 2.1 mL, 0.9 mL, respectively (P = .12); concentration-63.6 M/mL, 39.0 M/mL, 2.4 M/mL, respectively (P < .01); percent motility-51.5%, 34.3%, 15.6%, respectively (P < .01); and the total motile count was 63.2 M,39.1 M, 0.2 M, respectively (P < .01). Fifteen specimens were collected after discontinuing hormonal medication with a mean discontinuation period of 4.4 months. CONCLUSION Specimens collected in the presence of hormonal medication were associated with abnormal semen parameters. Specimens collected after discontinuation of gender-affirming treatments were comparable to transgender women who had never used hormonal medication. Transgender women should be counseled about the potential impact of gender-affirming hormones and to consider fertility preservation prior to gender-affirming treatments.

Women with polycystic ovary syndrome demonstrate worsening markers of cardiovascular risk over the short-term despite declining hyperandrogenaemia: Results of a longitudinal study with community controls

To compare age‐associated changes in cardiovascular risk markers in lean and obese reproductive‐aged women with polycystic ovary syndrome (PCOS) with community controls.