Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience.

PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

Assessing the impact of semen quality on embryo development in an egg donation model.

OBJECTIVE: To investigate if any of the World Health Organization semen parameters and/or male age are associated with embryo development. DESIGN: Retrospective chart review between January 2008 and May 2015. SETTING: Academic fertility practice. PATIENTS: Anonymous egg donors aged ≤30 years. INTERVENTIONS: Chart review. MAIN OUTCOME MEASURES: Sperm parameters were evaluated on a continuum and were dichotomized to determine if low values (strict morphology < 4%, concentration < 15 × 106, low motility < 40%) or older age (>50 years) are associated with embryo morphology. Repeated linear regression measures to determine the associations and multivariate testing to determine independent effects for each predictor were performed. RESULTS: Three hundred eighty-four donors with 574 egg donation cycles were identified, and 205 subjects with 275 cycles were included in the final analysis. The mean donor age was 25.31 ± 2.81 years, with a mean antral follicle count of 28.09 ± 10.5. The mean male age was 43.25 ± 6.65 years. The mean World Health Organization semen parameters at fertilization were 55.8 × 106 ± 44.3 × 106/mL concentration, 44.8% ± 20.2% motility, and 6.9% ± 5.3% strict morphology. Neither male age nor sperm morphology was associated with embryo morphology. A low total motile count was significantly associated with a higher cell number in day-3 embryos and a 1.56-times higher chance of poor day-3 cell symmetry. There was no statistically significant difference in blastocyst formation, clinical pregnancy, or live-birth rates. CONCLUSIONS: Although statistically significant, the effect of the low total motile count on day-3 cell number and cell symmetry are likely clinically insignificant. Male age, race, or poor sperm morphology were not associated with a poor cycle outcome or impaired embryo development. The use of intracytoplasmic sperm injection likely alleviates the negative effect of diminished semen quality on treatment outcome.

Predictors of adequate physical activity within a multiethnic polycystic ovary syndrome patient population: a cross-sectional assessment.

BACKGROUND: Physical activity is a cornerstone for treatment of women with polycystic ovary syndrome (PCOS), but there are limited data on their exercise behaviors. A previous study identified PCOS patients of non-White ethnicity to be at higher risk for inadequate physical activity. Further data is needed to identify groups that would benefit from additional counseling in achieving adequate physical activity (APA). Therefore, this study examined correlates of APA within a multiethnic PCOS patient population. METHODS: Cross-sectional assessment of exercise behaviors within a multiethnic PCOS patient population was performed using the International Physical Activity Questionnaire (IPAQ). Kruskal-Wallis test was used to compare metabolic equivalents from physical activity among racial/ethnic groups. APA was defined as at least 150 min of moderate-intensity, or 75 min of vigorous-intensity, or an equivalent combination of moderate- and vigorous-intensity activity per week. Logistic regression analyses were performed to identify correlates of APA. RESULTS: Four hundred and sixty-five women of various racial/ethnic backgrounds were included in analysis: 62% (n = 287) self-identified as White, 15% (n = 71) as Hispanic, 11% (n = 52) as East/Southeast Asian, 7% (n = 32) as South Asian, and 5% (n = 23) as Black/African American. Significant differences were observed in metabolic equivalents (METs) from vigorous-intensity and total (moderate plus vigorous-intensity) exercise across racial/ethnic groups (p < 0.01); South Asian patients had the lowest metabolic expenditure in moderate-intensity, vigorous-intensity, and total exercise. Overall prevalence of APA was 66%; South Asian patients exhibited the lowest prevalence (46.9%). Ethnicity was a predictor for APA when controlled for age (p = 0.01); this finding was attenuated in logistic regression models that also controlled for age and body mass index (p = 0.05) as well as education level and parity (p = 0.16). CONCLUSIONS: South Asian patients with PCOS exhibited the lowest metabolic expenditure and frequency of APA in our cohort. Differences in frequency of APA across racial/ethnic groups appear to be influenced by anthropometric and sociodemographic factors. Our findings present an opportunity for women's health providers to be cognizant and provide additional counseling regarding physical exercise to at-risk PCOS patients to improve their known higher risk for adverse long-term metabolic outcomes.

Comparison of metabolic syndrome elements in White and Asian women with polycystic ovary syndrome: results of a regional, American cross-sectional study.

OBJECTIVE: To examine differences in metabolic dysfunction between White, East Asian, and South Asian women with polycystic ovary syndrome (PCOS) living in the San Francisco Bay Area, California. DESIGN: Cross-sectional study. SETTING: Referral clinic at an academic center. PATIENTS: A total of 243 White, 25 South Asian, and 38 East Asian women with PCOS, according to the Rotterdam criteria, aged 14-57 years, were recruited from May 2006 to May 2017. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Fasting and 2-hour insulin and glucose, homeostasis model assessment of insulin resistance, and fasting lipids. Metabolic syndrome and its five individual components were defined according to the National Cholesterol Education Program Adult Treatment Panel guidelines. RESULTS: Median baseline body mass index (25.9 vs. 24.8 vs. 24.0 kg/m2) and age (28.3 vs. 25.2 vs. 29.4 years) did not differ between White, South Asian, and East Asian women. Two-hour insulin levels were elevated in East and South Asian women at >25-30 and >30 years, respectively, compared with White women in the same age groups. Two-hour glucose level was also elevated in East Asian women compared with White women at age >30 years. No other differences were detected in continuous metabolic markers or in the risk of metabolic syndrome and its components across the three race categories. CONCLUSIONS: White, South Asian, and East Asian women with PCOS living in the same geographic region have comparable metabolic profiles to one another, although Asian women have higher 2-hour insulin levels and East Asian women, in particular, have higher 2-hour glucose levels.

Effect of culture conditions and method of conception on mouse live birth rate.

OBJECTIVE: To understand in a mouse model whether there are differences in the decidua and live birth rate after transfer of blastocysts generated by in vitro fertilization (IVF) or by superovulation with spontaneous mating into unstimulated recipients. DESIGN: Animal experiment. SETTING: University-affiliated tertiary hospital. ANIMAL(S): Mice. INTERVENTION(S): IVF embryos were generated and cultured in either Whitten medium (WM, suboptimal conditions) and 20% O2 or KSOM medium with amino acids (KAA, optimal conditions) and 5% O2. The control blastocysts from superovulated mice were flushed out of the uterus 3.5 days (E3.5) after mating (FB group). The resulting blastocysts were transferred to nonsuperovulated CF1 recipients mated to vasectomized males. To understand whether anomalies of decidua were present, the expression of genes involved in decidual development and inflammation was analyzed at E7.5 and E18.5. Similarly, immunostaining was used to evaluate whether the pathways involved in activation of mTORC1 (p-S6) and Cox2 signaling (Cox 2 staining) were altered. MAIN OUTCOME MEASURE(S): Live birth rate, gene expression, and immunostaining of decidua. RESULT(S): Implantation rates at E7.5 were similar, but in vivo embryos (FB groups) were predicted to result in live births 3.3 times higher (2.2-5.1) and 6.6 times higher (4.7-9.3) compared with optimal and suboptimal cultures, respectively. Expression of genes involved in decidual development and inflammation or localization and intensity of staining for p-S6 (mTOR pathway), or inflammation (Cox 2 pathway) were not different among the groups. CONCLUSION(S): The predicted live birth rate was decreased in mouse embryos generated by IVF compared with embryos generated by mating, whereas the implantation rate was not different. Suboptimal culture conditions resulted in lower birth rate. We did not find evidence of abnormalities in decidualization that could explain these findings. These data indicate that blastocysts cultured in stressful conditions are less competent, suggesting that decreasing the number of embryonic manipulations may result in higher live birth rates.

Improved diagnostic performance for the diagnosis of polycystic ovary syndrome using age-stratified criteria.

OBJECTIVE: To determine optimal criteria for polycystic ovary morphology. DESIGN: Cross-sectional study. SETTING: Multidisciplinary polycystic ovary syndrome (PCOS) clinic at a tertiary academic center. PATIENT(S): Subjects with PCOS were seen between 2006 and 2015 and met PCOS 1992 National Institutes of Health criteria. Controls were from the Ovarian Aging (OVA) study (2006-2011), a longitudinal study including healthy women with regular menstrual cycles. INTERVENTION(S): Clinical data collection. MAIN OUTCOME MEASURE(S): Follicle number per ovary (FNPO) and ovarian volume (OV). RESULT(S): A total of 245 subjects with PCOS and 756 OVA study subjects were included in the FNPO analysis and had a mean (± SD) FNPO of 22.6 ± 12.4 and 10 ± 5.3, respectively. Receiver operating characteristic curves were created for both FNPO and OV and analyzed across age group categories (25 to <30, 30 to <35, and 35 to <40 years). Youden's and minimum distance (d) were used to compare efficacies of FNPO and OV thresholds. The optimal threshold for distinguishing PCOS from OVA controls was FNPO > 13. There was a decreasing trend in FNPO threshold with increasing age group (>15, >14, and >12, respectively). A total of 297 PCOS subjects and 756 OVA study subjects were included in the OV analysis and had a mean maximum OV of 10 ± 5 cm3 and 6.5 ± 5 cm3, respectively. The overall threshold was OV > 6.75 cm3, with a trend toward decreasing OV with increase in age group (>8.5, >7, and >6.25 cm3, respectively). CONCLUSION(S): Our findings reflect that age-stratified thresholds demonstrate superior diagnostic performance, with an improved balance of sensitivity and specificity compared with a single threshold. We propose age-specific thresholds for better diagnostic performance.

Semen Parameters Among 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.

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.

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.

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.

OBJECTIVE: To compare age-associated changes in cardiovascular risk markers in lean and obese reproductive-aged women with polycystic ovary syndrome (PCOS) with community controls. DESIGN: Longitudinal study at an academic medical centre PATIENTS: Patients diagnosed with PCOS by 2004 Rotterdam criteria in a multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS cohort study and subsequently agreed to participate in a longitudinal study. The comparison controls were from the prospective, longitudinal Ovarian Aging (OVA) study, which consists of healthy women with regular menstrual cycles recruited from 2006 to 2011. MEASUREMENTS: Cardiovascular risk markers and hormone parameters at baseline and follow-up. RESULTS: Obese and lean PCOS (n = 38) and control women (n = 296) completed two study visits. The follow-up time (3.5 ± 1.5 vs 4.0 ± 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m2 /y [-0.11, 0.36] vs +0.26 [-0.18, 0.87] P = .19) did not differ between obese and lean PCOS and controls. In PCOS subjects, total testosterone decreased in both obese and lean, but the decrease was greater in obese subjects (-0.09 nmol/L per year; 95% CI: -0.16, -0.02 vs -0.04 nmol/L per year; 95%CI: -0.11, 0.03). Compared to their respective controls, obese and lean PCOS saw worsening triglyceride (TG) levels (P < .05) and HOMA-IR (P < .05) over time, but there was no difference in change in LDL, HDL, fasting glucose, C-reactive protein or ALT. CONCLUSIONS: In a longitudinal study, reproductive-aged women with PCOS demonstrated declines in biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced steeper increases in cardiovascular risk factors associated with insulin resistance, including triglycerides and HOMA-IR.

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

OBJECTIVE: 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. DESIGN: Cross-sectional study at academic medical centres across the United States. PATIENTS: Women with PCOS were diagnosed by Rotterdam criteria and included 282 subjects from the multisite PPCOS II trial and 109 patients from a tertiary academic centre's multidisciplinary PCOS clinic. Controls included 245 participants in the ovarian ageing (OVA) study, a community-based cohort of ovulatory women not seeking treatment for fertility. MEASUREMENTS: Determination of AMH by a central laboratory. Receiver-operating characteristic (ROC) analyses were used to investigate the accuracy of AMH thresholds for prediction of PCOS diagnosis with stratification by age. RESULTS: The optimal threshold of AMH to distinguish PCOS from controls was 55.36 pmol/L (sensitivity: 0.82, specificity: 0.78, J: 0.60). When examining the population by age groups, the optimal AMH threshold decreased with increasing age. CONCLUSIONS: AMH is an effective biomarker of PCOS. Age-stratified thresholds more accurately predicted PCOS than an overall population-based threshold.

Ovarian morphology is associated with insulin resistance in women with polycystic ovary syndrome: a cross sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a very common disorder well known to be associated with insulin resistance and metabolic disease. Insulin resistance is likely involved in the promotion of the PCOS reproductive phenotype and may mediate some of the ovarian morphology seen in the disorder. The phenotype of each individual woman with PCOS can vary widely as can her metabolic risk. METHODS: This is a cross-sectional study of patients seen in a multidisciplinary PCOS clinic at the University of California at San Francisco between 2006 and 2014. All participants underwent systematic evaluation with anthropometric measurements, comprehensive skin exam, transvaginal ultrasound and laboratory studies at the time of their initial visit to the clinic. Serum samples were stored and androgen studies were carried out on all stored samples at the University of Virginia. Logistic regression was employed to evaluate the association between ovarian volume or follicle number and metabolic parameters (fasting insulin, HOMA-IR, fasting glucose, 2 h glucose, waist circumference) and hyperandrogenism (free testosterone, total testosterone, DHEAS, acanthosis nigricans), controlling for age. RESULTS: Three-hundred thirteen patients seen during the study period met Rotterdam criteria for PCOS and had sufficient measurements for inclusion in our analysis. The odds ratio of elevated HOMA-IR for patients with a maximum ovarian volume >10 cc was 1.9 compared to those with a maximum ovarian volume of ≤10 cc (95% CI 1.0-3.4). The odds ratio of abnormal fasting insulin for patients with higher ovarian volume was 1.8 (95% CI 1.0-3.4) compared with those with lower ovarian volume. Follicle number was not significantly associated with any metabolic parameters. CONCLUSIONS: Increased ovarian volume is associated with markers of insulin resistance in PCOS. In concordance with prior studies, we did not find follicle number to be predictive of metabolic risk. Ovarian volume may serve as a useful tool to aid clinicians in their risk stratification and counseling of patients with PCOS.

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 Society's 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.

Vigorous exercise is associated with superior metabolic profiles in polycystic ovary syndrome independent of total exercise expenditure.

OBJECTIVE: To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. DESIGN: Cross-sectional study. SETTING: Tertiary academic institution. PATIENT(S): Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013. INTERVENTION(S): International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. MAIN OUTCOME MEASURE(S): Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). RESULT(S): The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99). CONCLUSION(S): Women with PCOS who met DHHS guidelines for exercise demonstrated superior metabolic health parameters. Vigorous but not moderate activity is associated with reduced odds of the metabolic syndrome, independent of age, BMI, and total energy expenditure. PCOS patients should be encouraged to meet activity guidelines via vigorous physical activity.

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.

Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer.

The impact of long-term tamoxifen therapy on ovarian function is not known. Understanding these effects will help reproductive-aged patients who desire future pregnancy make more informed decisions regarding their treatment. This is a retrospective cohort study in patients identified through the UCSF Cancer Registry and SPORE database. We enrolled women with a history of ductal carcinoma in situ (DCIS) or early stage invasive breast cancer who were premenopausal at diagnosis and did not receive chemotherapy. Menstrual histories were obtained through electronic and paper surveys. We compared the age of menopause onset and menstrual pattern changes between women who received tamoxifen (TAM) and those who did not receive tamoxifen (control). Neither group received chemotherapy. 250 subjects were included in this study (125 TAM, 125 control). Mean age of menopause onset was 51.0 for both the groups and was not associated with duration of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes, including amenorrhea, were more frequent in the TAM group than control group (any change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control, p < 0.001). Older age was associated with an increased risk of developing amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use in the absence of chemotherapy is not associated with an earlier age onset of menopause in patients with DCIS or invasive breast cancer and is unlikely to significantly accelerate ovarian aging.

Behavior and brain gene expression changes in mice exposed to preimplantation and prenatal stress.

Preimplantation culture of mouse embryos has been suggested to result in reduced anxiety-like behavior in adulthood. Here, we investigated the effects of in vitro fertilization (IVF), embryo culture, and different diets on anxiety-like behavior using the elevated plus maze (EPM). We hypothesized that exposure to suboptimal conditions during the preimplantation stage would interact with the suboptimal diet to alter behavior. The expression of genes related to anxiety was then assessed by quantitative real-time polymerase chain reaction in various brain regions. When fed a normal diet during gestation and a moderately high-fat Western diet (WD) postnatally, naturally conceived (NC) and IVF mice showed similar anxiety-like behavior on the EPM. However, when fed a low-protein diet prenatally and a high-fat diet postnatally (LP/HF), NC mice showed a modest increase in anxiety-like behavior, whereas IVF mice showed the opposite: a strongly reduced anxiety-like behavior on the EPM. The robust reduction in anxiety-like behavior in IVF males fed the LP/HF diets was, intriguingly, associated with reduced expression of MAO-A, CRFR2, and GABA markers in the hypothalamus and cortex. These findings are discussed in relation to the developmental origin of health and disease hypothesis and the 2-hit model, which suggests that 2 events, occurring at different times in development, can act synergistically with long-term consequences observed during adulthood.

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

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.

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.