Associations of Polycystic Ovary Syndrome With Indicators of Brain Health at Midlife in the CARDIA Cohort.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with an adverse cardiometabolic profile early in life. Increasing evidence links cardiovascular risk factors, such as diabetes and hypertension, to accelerated cognitive aging. However, less is known about PCOS and its relationship to brain health, particularly at midlife. Our goal was to investigate possible associations between PCOS and midlife cognitive function and brain MRI findings in an ongoing prospective study. METHODS: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a geographically diverse prospective cohort study of individuals who were 18-30 years at baseline (1985-1986) and followed for 30 years. We identified women with PCOS from an ancillary study (CARDIA Women's study (CWS); n = 1,163) as those with elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhea. At year 30, participants completed cognitive testing, including the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory), Digit Symbol Substitution Test (processing speed and executive function), Stroop test (attention and cognitive control), and category and letter fluency tests (semantics and attention). A subset completed brain MRI to assess brain structure and white matter integrity. Multivariable linear regression models estimated the association between PCOS and outcomes, adjusting for age, race, education, and study center. RESULTS: Of the 1163 women in CWS, 907 completed cognitive testing, and of these, 66 (7.1%) met criteria for PCOS (age 54.7 years). Women with and without PCOS were similar for age, BMI, smoking/drinking status, and income. At year 30, participants with PCOS performed lower (mean z score; 95% CI) on Stroop (-0.323 (-0.69 to -7.37); p = 0.008), RAVLT (-0.254 (-0.473 to -0.034); p = 0.002), and category fluency (-0.267 (-0.480 to -0.040); p = 0.02) tests. Of the 291 participants with MRI, 25 (8.5%) met PCOS criteria and demonstrated lower total white matter fractional anisotropy, a measure of white matter integrity (coefficient (95% CI) -0.013 (-0.021 to -0.005); p = 0.002), though not abnormal white matter. DISCUSSION: Our results suggest that women with PCOS have lower cognitive performance and lower white matter integrity at midlife. Additional research is needed to confirm these findings and to determine potential mechanistic pathways including potential modifiable factors.

Platelet-rich plasma infusion as an adjunct treatment for persistent thin lining in frozen embryo transfer cycles: first US experience report.

PURPOSE: To study effect of intrauterine infusion of platelet-rich plasma (PRP) on endometrial growth in the setting of thin endometrial lining in patients with prior cancelled or failed frozen embryo transfer (FET) cycles. MATERIALS AND METHODS: Single-arm cohort study of forty-six patients (51 cycles) with endometrial lining thickness (EMT) < 6 mm in prior cancelled or failed FET cycles requesting intrauterine PRP treatment in upcoming FET cycle. The primary outcomes were final EMT in FET cycle and change in EMT after PRP. The secondary outcomes were overall pregnancy rate, clinical pregnancy rate, miscarriage rate, ongoing pregnancy, and live birth rates. RESULTS: The mean pre-PRP EMT in all FET cycles was 4.0 ± 1.1 mm, and mean post-PRP EMT (final) was 7.1 ± 1.0 mm. Of 51 cycles, 33 (64.7%) reached ≥ 7 mm after PRP administration. There was a significant difference between pre-PRP EMT and post-PRP EMT in all FET cycles, with mean difference of 3.0 ± 1.5 mm. Three cycles were cancelled for failure to reach adequate lining. Total pregnancy rate was 72.9% in our cohort of 48 cycles that proceeded to transfer. Clinical pregnancy rate was 54.2% (26/48 FET cycles); clinical miscarriage rate was 14.3% (5/35 pregnancies). Twenty six women had live birth (18 with EMT ≥ 7 mm and 8 with EMT < 7 mm). Response to PRP was not correlated with any pre-cycle characteristics. CONCLUSION: We demonstrate a significant improvement in lining thickness and pregnancy rates in this challenging cohort of women after PRP infusion, with no adverse events. Cost-effectiveness of PRP with benefits and alternatives should be carefully considered.

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.

Association of obstructive sleep apnea risk with depression and anxiety symptoms in women with polycystic ovary syndrome.

STUDY OBJECTIVE: To determine whether obstructive sleep apnea (OSA) risk is associated with depression and anxiety symptoms in women with polycystic ovary syndrome (PCOS). METHODS: This is a cross-sectional study of women with PCOS, by the Rotterdam criteria, seen at a single academic center between June 2017 and June 2020. Depression symptoms, anxiety symptoms, and OSA risk were assessed with the self-administered Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Berlin questionnaires, respectively. Univariate and multivariate logistic regression analyses were used to determine the odds of moderate/severe symptoms of depression (PHQ-9 ≥ 10) and anxiety (GAD-7 ≥ 10) in the high-risk vs low-risk OSA groups. The primary multivariate model adjusted for age, body mass index, free testosterone, and insulin resistance. RESULTS: Of the 200 participants, the mean age was 28.0 years and 38% screened high risk for OSA. Women who screened high-risk OSA had > 3 times the odds of moderate/severe depression (odds ratio [OR]: 3.19; 95% confidence interval [CI]: 1.76-5.78; P < .001) and > 2 times the odds of having moderate/severe anxiety (OR: 2.49; 95% CI: 1.34-4.64; P = .004). These associations were only slightly attenuated in the adjusted models: the adjusted OR for moderate/severe depression was 3.06 (95% CI: 1.36-6.88; P = .01) and the aOR for moderate/severe anxiety was 2.39 (95% CI: 1.03-5.59; P = .04). CONCLUSIONS: Among women with PCOS, those at high risk of OSA experienced elevated depression and anxiety symptoms compared with those at low risk for OSA, independent of the effects of age, body mass index, hyperandrogenism, and insulin resistance. CITATION: Zhou X, Jaswa E, Pasch L, Shinkai K, Cedars MI, Huddleston HG. Association of obstructive sleep apnea risk with depression and anxiety symptoms in women with polycystic ovary syndrome. J Clin Sleep Med. 2021;17(10):XXX-XXX.

Highly elevated level of antimüllerian hormone associated with preterm delivery in polycystic ovary syndrome patients who underwent ovulation induction.

OBJECTIVE: To determine the relationship between high antimüllerian hormone (AMH) levels and increased preterm delivery risk in populations of women with polycystic ovary syndrome (PCOS) or unexplained infertility undergoing ovulation induction. DESIGN: Secondary analysis of data from two multicenter randomized clinical trials: Pregnancy in Polycystic Ovary Syndrome II (PPCOS II); and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS). SETTING: Not applicable. PATIENTS: Live births at ≥24 weeks' gestation from both the PPCOS II (n = 172) and AMIGOS (n = 222) cohorts were evaluated, and those at risk for iatrogenic preterm delivery including placental conditions, fetal growth restriction, multiple gestations, hypertensive diseases of pregnancy, and pre-gestational diabetes were excluded. The final analysis included 118 women with PCOS from the PPCOS II cohort and 146 women with unexplained infertility from the AMIGOS cohort. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Spontaneous preterm delivery. RESULTS: In the PCOS population, median AMH overall was 5.5 ng/dL (interquartile range 2.9-9.3 ng/dL). In all, 62% of participants who delivered preterm had AMH levels above the 75th percentile. When comparing clinical covariates between the preterm and term deliveries, women with PCOS who delivered preterm had notably higher AMH than their term counterparts (11.1 vs. 5.4 ng/mL). In the univariate logistic regression analysis, each unit increase in AMH raised the odds of preterm delivery by 14% (odds ratio 1.14, 95% confidence interval 1.02-1.26). The effect was magnified only after adjusting for age, race, body mass index, smoking status, testosterone, homeostatic model assessment for insulin resistance, and treatment randomization group (adjusted odds ratio 1.25, 95% confidence interval 1.06-1.49). Unlike in the PCOS population, the unexplained infertility cohort had no significant difference in AMH levels between those with or without preterm delivery (2.3 vs. 2.6 ng/mL). CONCLUSIONS: Our findings suggest that women with PCOS and high AMH who conceived after ovulation induction represent a high-risk group for preterm delivery. These data indicate that closer monitoring in the third trimester of pregnancies in PCOS patients with early first trimester AMH levels above 9.3 ng/mL may be warranted. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.

Increased Body Mass Index Is Associated With A Nondilutional Reduction in Antimüllerian Hormone.

CONTEXT: Controversy exists regarding if and how body mass index (BMI) impacts antimüllerian hormone (AMH) in women with and without polycystic ovary syndrome (PCOS). Understanding the BMI-AMH relationship has critical implications for clinical interpretation of laboratory values and could illuminate underlying ovarian physiology. OBJECTIVE: To test the hypotheses that (1) BMI is associated with reduced AMH in PCOS and ovulatory controls (OVAs) and (2) the reduction in AMH is not accounted for by dilutional effects. DESIGN/SETTING: Multicenter cohort. PARTICIPANTS: Women aged 25 to 40 years from 2 clinical populations: 640 with PCOS, 921 women as OVAs. MAIN OUTCOME MEASURES: Ovarian reserve indices: AMH, antral follicle count (AFC), and AMH to AFC ratio (AMH/AFC) as a marker of per-follicle AMH production. RESULTS: In both cohorts, increasing BMI and waist circumference were associated with reductions in AMH and AMH/AFC, after adjusting for age, race, smoking, and site in multivariate regression models. Increasing BMI was associated with reduced AFC in PCOS but not OVAs. Body surface area (BSA), which unlike BMI is strongly proportional to plasma volume, was added to investigate a potential dilutive effect of body size on AMH concentrations. After controlling for BSA, BMI retained independent associations with AMH in both cohorts; BSA no longer associated with AMH. CONCLUSIONS: In an adjusted analysis, BMI, but not BSA, was associated with reduced AMH; these data do not support a role for hemodilution in mediating the relationship between increased body size and reduced AMH. Decreased AMH production by the follicle unit may be responsible for reduced AMH with increasing BMI.

Obesity and depression are risk factors for future eating disorder-related attitudes and behaviors in women with polycystic ovary syndrome.

OBJECTIVE(S): To identify clinical predictors of future eating disorder symptoms in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: University center. PATIENT(S): One hundred sixty-four women with PCOS by the Rotterdam criteria. INTERVENTION(S): Participants were characterized at a baseline visit between 2006 and 2017. A questionnaire including the validated Eating Disorder Examination-Questionnaire (EDE-Q) was self-administered at follow-up. MAIN OUTCOME MEASURE(S): EDE-Q global score (0-6, higher scores indicate more severe symptoms). RESULT(S): One hundred sixty-four women completed the follow-up survey an average of 5.3 years after the baseline visit. Compared with a normative population, women with PCOS had higher EDE-Q global scores (2.3 vs. 1.5) and scored higher on all subscales. Within the PCOS cohort, the following baseline clinical characteristics were independently predictive of scoring in the highest EDE-Q global score tertile: body mass index, waist circumference, hyperandrogenemia, high sensitivity C-reactive protein, and depression scores. Obesity at baseline conferred a 6.9-fold increase in the odds of elevated EDE-Q score (adjusted odds ratio = 6.89; 95% confidence interval, 2.70, 17.62), while a positive depression screen conferred 3.6-fold increased odds (adjusted odds ratio = 3.58; 95% confidence interval, 1.74-7.35). Compared with white women, nonwhite women were at risk of higher EDE-Q scores. CONCLUSION(S): Women with PCOS are at risk of disordered eating attitudes and behaviors, which may interfere with attempts at lifestyle interventions. Clinicians should screen women with PCOS for eating disorder psychopathology, especially those with obesity or depression. An exclusive focus on weight loss may have unintended consequences.

Associations Between Anti-Mullerian Hormone and Cardiometabolic Health in Reproductive Age Women Are Explained by Body Mass Index.

CONTEXT: The relationship between reproductive and cardiometabolic aging is unclear. It is unknown if the relationship differs across different clinical populations. OBJECTIVE: To determine whether markers of ovarian reserve are associated with cardiometabolic risk in reproductive aged women with unexplained infertility (UI), polycystic ovary syndrome (PCOS), and regularly cycling women (OVA). DESIGN AND SETTING: Cross-sectional data from 8 US-based academic centers. PARTICIPANTS: Women aged 25-40 from 3 clinical populations: 870 with UI, 640 with PCOS, and 921 community-based OVA. MAIN OUTCOME MEASURES: Multivariable linear regression models were used to relate anti-mullerian hormone (AMH) and antral follicle count with cardiometabolic parameters including body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment-insulin resistance (HOMA-IR), lipids, and C-reactive protein. RESULTS: In age and study site-adjusted models, AMH inversely related to BMI in the UI and OVA groups (P = 0.02 and P < 0.001). Among women with PCOS, AMH inversely related to BMI (P < 0.001), and also to WC (P < 0.001), fasting insulin (P < 0.01), HOMA-IR (P < 0.01), triglycerides (P = 0.04), and C-reactive protein (P < 0.001) and directly related to higher total (P = 0.02), low-density lipoprotein (P < 0.01), and high-density lipoprotein cholesterol (P < 0.01). In OVA, AMH also varied inversely with WC (P < 0.001), fasting insulin (P = 0.02), and HOMA-IR (P = 0.02). Adjustment for BMI eliminated associations in the OVA group but in PCOS, the relationship of AMH to total (P = 0.03) and low-density lipoprotein cholesterol (P = 0.003) remained. CONCLUSION: Associations observed between AMH and cardiometabolic indices are largely explained by BMI in women with and without PCOS. (J Clin Endocrinol Metab XX: 0-0, 2019).

Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD). METHODS: Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status. RESULTS: Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2 , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02). CONCLUSION: Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.

Depression Over the Lifespan in a Population-Based Cohort of Women With Polycystic Ovary Syndrome: Longitudinal Analysis.

OBJECTIVE: To (i) determine whether women with polycystic ovary syndrome (PCOS) from a population-based cohort experience elevated depression symptoms and (ii) characterize the trajectory of symptoms over the lifespan. DESIGN: The association between PCOS and longitudinal depression scores was investigated among 1127 black and white women participating in Coronary Artery Risk Development in Young Adults study. PCOS was ascertained at baseline (ages 20 to 32) by U.S. National Institutes of Health (NIH) criteria, incorporating androgens and symptoms of oligomenorrhea and hirsutism. The Center for Epidemiologic Studies-Depression (CES-D) scale was repeated prospectively in 5-year intervals over 25 years. Mixed-effects models evaluated the association between depression scores and PCOS after adjustment for confounders and characterized the trajectory of scores. The impact of race was explored. RESULTS: Eighty-three of 1127 (7.4%) participants met NIH PCOS criteria. Of these, 33 (40%) were black and 50 (60%) were white. CES-D scores were higher among women with PCOS [coefficient (coef) 2.51; 95% CI 1.49, 3.54; P < 0.01] across the lifespan. Scores decreased across the lifespan in women with and without PCOS (coef -0.1 point per year; P < 0.001). Black women experienced higher depression burden than white women (coef 1.80; 95% CI 1.20, 2.41; P < 0.001); however, an interaction was not detected between PCOS and race (P = 0.68). CONCLUSIONS: Women with PCOS-NIH from a population-based cohort are at risk for higher depression scores across the lifespan. Depression scores decline over time in women with PCOS in a trajectory similar to that in women without PCOS. Racial differences in depression risk should be acknowledged clinically and further explored.

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.

Clinical course of depression symptoms and predictors of enduring depression risk in women with polycystic ovary syndrome: Results of a longitudinal study.

OBJECTIVE: To [1] characterize depression symptoms over time and [2] test the hypothesis that adverse metabolic parameters would associate with risk of enduring depression risk in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: University center. PATIENT(S): One hundred sixty-three women with PCOS. INTERVENTION(S): The Beck Depression Inventory Fast Screen (BDI-FS) was self-administered at baseline and follow-up to identify depression risk, using a cutoff score >4. MAIN OUTCOME MEASURE(S): BDI-FS scores. RESULT(S): Median baseline age was 29.0 years, and median follow-up interval was 5.5 years. Fifty-nine of 163 women had positive depression screens at baseline (36%); 52 women (32%) screened positive at follow-up. Median change in BDI-II score was 0 (interquartile range, -2, 1) over the study period. Of the 59 women at risk for depression at baseline, 22 screened negative at follow-up (37%), while 37 women remained at risk (63%). Considering these 59 women with positive depression screens at baseline, higher body mass index (BMI) was associated with increased odds of enduring depression risk at follow-up (adjusted odds ratio = 1.09; 95% confidence interval, 1.00, 1.18), in a multivariate logistic regression model. Compared with women with normal body weight at baseline, obese women (BMI >30 kg/m2) had five-fold increased odds of enduring depression risk at follow-up (adjusted odds ratio = 5.07; 95% confidence interval, 1.07, 24.0). CONCLUSION(S): The prevalence of depression was relatively stable over time in a cohort of women with PCOS. Elevated BMI is a hallmark of enduring depression risk. These results may assist providers in developing targeted intervention strategies to reduce the prevalence of long-term depressive symptoms in women with PCOS.

Association among depression, symptom experience, and quality of life in polycystic ovary syndrome.

BACKGROUND: Clinical stigmata of polycystic ovary syndrome include hirsutism, obesity, menstrual disturbances, and infertility. These symptoms impair health-related quality of life. Depression is also common. The relationship among depression, symptom self-perception, and quality of life in polycystic ovary syndrome is poorly understood. OBJECTIVE: We sought to investigate the relationship between health-related quality of life and depression in women with polycystic ovary syndrome. STUDY DESIGN: We conducted a secondary analysis of a multicenter, randomized clinical trial (Pregnancy in Polycystic Ovary Syndrome II, NCT00719186) comparing clomiphene citrate vs letrozole in the treatment of infertility. Subjects included 732 women ages 18-40 years with polycystic ovary syndrome by modified Rotterdam criteria. The validated Polycystic Ovary Syndrome Health-Related Quality of Life survey was self-administered, assessing the following domains: emotions, body hair, body weight, menstrual problems, and infertility; scores range from 1-7, with lower numbers indicating poorer quality of life. Depression was evaluated via the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire. Quality-of-life scores were compared between depressed and nondepressed women. Multivariate linear regression models analyzed the association between depression and quality-of-life scores, controlling for age, body mass index, hirsutism score, and duration of infertility. RESULTS: In all, 64 women (8.4%) met criteria for depression. Depressed women reported reduced quality of life in all domains compared to nondepressed women: mood (3.1 vs 4.6, P < .001), body hair (3.5 vs 4.2, P = .002), weight (2.0 vs 3.5, P < .001), menstrual problems (3.3 vs 4.1, P < .001), and infertility (1.9 vs 3.0, P < .001). Global quality-of-life score was reduced in depressed women (2.8 vs 3.9, P < .001). Impairments in quality of life in depressed women persisted in all domains after controlling for objective parameters including age, body mass index, hirsutism score, and infertility duration. CONCLUSION: Depression is associated with reduced quality of life related to polycystic ovary syndrome symptoms. Disturbances in health-related quality of life in depressed women are not explained by objective measures including body mass index, hirsutism scores, and duration of infertility. Depression may color the experience of polycystic ovary syndrome symptoms and should be considered when there is significant discordance between subjective and objective measures in women with polycystic ovary syndrome.

Insulin resistance is associated with depression risk in polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that insulin resistance is associated with depression risk in polycystic ovary syndrome (PCOS). DESIGN: Secondary analysis of data from a multicenter randomized trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): Seven hundred thirty-eight women with PCOS by modified Rotterdam criteria seeking pregnancy enrolled in a randomized clinical trial comparing clomiphene citrate versus letrozole. INTERVENTION(S): The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire was self-administered to identify depression using a validated algorithm at enrollment. Demographic and anthropometric data were collected, and serum assays were performed. Insulin resistance was estimated using the homeostatic model of insulin resistance (HOMA-IR), with a cutoff of >2.2 considered abnormal. MAIN OUTCOME MEASURE(S): Demographic, endocrine, and metabolic parameters associated with depression. RESULT(S): In a univariate logistic regression analysis, elevated HOMA-IR was associated with 2.3-fold increased odds of depression (odds ratio [OR] = 2.32; 95% confidence interval [CI], 1.28-4.21). This association remained significant after controlling for age and body mass index (adjusted OR [aOR] = 2.23; 95% CI, 1.11-4.46) and in a model including additional potential confounders (aOR = 2.03; 95% CI, 1.00-4.16). CONCLUSION(S): Insulin resistance has a strong and independent association with depression in PCOS and may serve as a physiologic mediator. Our findings corroborate a growing body of evidence linking insulin resistance to depressed mood. The association between insulin resistance and depressed mood warrants further investigation to elucidate mechanisms and identify potential therapeutic targets.

In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration.

PURPOSE: The study aims to test the hypothesis that platelet-rich plasma (PRP) stimulates cellular processes involved in endometrial regeneration relevant to clinical management of poor endometrial growth or intrauterine scarring. METHODS: Human endometrial stromal fibroblasts (eSF), endometrial mesenchymal stem cells (eMSC), bone marrow-derived mesenchymal stem cells (BM-MSC), and Ishikawa endometrial adenocarcinoma cells (IC) were cultured with/without 5% activated (a) PRP, non-activated (na) PRP, aPPP (platelet-poor-plasma), and naPPP. Treatment effects were evaluated with cell proliferation (WST-1), wound healing, and chemotaxis Transwell migration assays. Mesenchymal-to-epithelial transition (MET) was evaluated by cytokeratin and vimentin expression. Differential gene expression of various markers was analyzed by multiplex Q-PCR. RESULTS: Activated PRP enhanced migration of all cell types, compared to naPRP, aPPP, naPPP, and vehicle controls, in a time-dependent manner (p < 0.05). The WST-1 assay showed increased stromal and mesenchymal cell proliferation by aPRP vs. naPRP, aPPP, and naPPP (p < 0.05), while IC proliferation was enhanced by aPRP and aPPP (p < 0.05). There was no evidence of MET. Expressions of MMP1, MMP3, MMP7, and MMP26 were increased by aPRP (p < 0.05) in eMSC and eSF. Transcripts for inflammation markers/chemokines were upregulated by aPRP vs. aPPP (p < 0.05) in eMSC and eSF. No difference in estrogen or progesterone receptor mRNAs was observed. CONCLUSIONS: This is the first study evaluating the effect of PRP on different human endometrial cells involved in tissue regeneration. These data provide an initial ex vivo proof of principle for autologous PRP to promote endometrial regeneration in clinical situations with compromised endometrial growth and scarring.

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.