A novel system for rapid conversion of Gardner embryo grades to linear scale numeric variables.

RESEARCH QUESTION: Can Gardner embryo grades be converted to numeric interval variables to improve the incorporation of embryo grading in statistical analyses? DESIGN: An equation that can be used to convert Gardner embryo grades to regular interval scale variables was developed: the numerical embryo quality scoring index (NEQsi). The NEQsi system was then validated with a retrospective chart analysis assessing IVF cycles (n = 1711) conducted at a single Canadian fertility centre between 2014 and 2022. Gardner embryo grades on file were assigned using EmbryoScope and converted to NEQsi scores. Descriptive statistics, univariate logistic regressions and generalized estimating equations with cycle outcomes were prepared to demonstrate the relationship between NEQsi score and probability of pregnancy. RESULTS: NEQsi produces interval numerical scores that range from 2 to 11. Patient case files in which single embryo transfers occurred (n = 1711) were examined and the Gardner embryo grades on file were converted to NEQsi scores. NEQsi scores ranged from 3 to 11, with a median score of 9. A positive linear relationship existed between the NEQsi scores and the probability of pregnancy (as assessed by quantitative ß-HCG). The NEQsi score was a significant predictor of pregnancy (P < 0.001). CONCLUSION: Gardner embryo grades can be converted to interval variables and used directly statistical analyses.

Dominant follicle growth patterns and associated endocrine dynamics in anovulatory and ovulatory waves in women.

Growth patterns and associated endocrine profiles were compared between dominant anovulatory (ADF) and ovulatory follicles (OvF) developing from different waves within and between menstrual cycles in women. Follicular mapping profiles of 49 healthy women of reproductive age and blood samples were obtained every 1-3 days. Sixty-three dominant follicles were classified into wave 1 (W1ADF; n = 8) and wave 2 (W2ADF; n = 6) anovulatory follicles and wave 2 (W2OvF; n = 33) and wave 3 (W3OvF; n = 16) ovulatory follicles. Comparisons were made between W1ADF and W2ADF, W2ADF and W2OvF, and W2OvF and W3OvF. The waves were numbered 1, 2, or 3 based on when the waves emerged relative to the preceding ovulation. W1ADF emerged closer to the preceding ovulation, and W2ADF emerged in the late luteal or early follicular phase. The interval from emergence to maximum diameter was shorter for W2ADF than W1ADF and for W3OvF than W2OvF. Selection of W3OvF occurred at a smaller diameter compared to W2OvF. W1ADF regressed at a faster rate than W2ADF. Also, W1ADF were associated with lower mean FSH and higher mean estradiol than W2ADF. In contrast, W3OvF were associated with higher FSH and LH compared to W2OvF. However, W2OvF were associated with higher progesterone than W3OvF. This study contributes to the understanding of the physiologic mechanisms underlying selection of the dominant follicle, ovulation, and pathophysiology of anovulation in women, as well as optimization of ovarian stimulation protocols for assisted reproduction.

A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions.

STUDY OBJECTIVE: To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans. DESIGN: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT). SETTING: Tertiary care gynecology surgical centre. PATIENTS: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL. INTERVENTIONS: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight. MEASUREMENTS: Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG. MAIN RESULTS: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed. CONCLUSIONS: Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.

Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive-aged women with polycystic ovary syndrome: A systematic review and meta-analysis of 45 observational studies.

Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is inconclusive. Altered muscle mass may aggravate PCOS complications. Our systematic review and meta-analysis evaluated whether PCOS alters muscle mass and function. Databases (MEDLINE, Web of Science, Scopus) were searched through September 2, 2020, for studies documenting skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Forty-five studies (n = 3676 participants) were eligible. Women with PCOS had increased total (0.83 [0.08,1.58] kg; p = 0.03; I2  = 72.0%) yet comparable trunk (0.84 [-0.37,2.05] kg; p = 0.15; I2  = 73.0%) LBM or FFM versus controls. Results of meta-regression analyses showed no associations between mean differences between groups in total testosterone or homeostatic model assessment of insulin resistance and total or trunk LBM or FFM (All: p ≥ 0.75). Mean differences in body mass index (BMI) were associated with total (0.65 [0.23,1.06] kg; p < 0.01; I2  = 56.9%) and trunk (0.56 [0.11,1.01] kg; p = 0.02; I2  = 42.8%) LBM or FFM. The PCOS subgroup with BMI ≥ 25 kg/m2 had greater total LBM or FFM versus controls (1.58 [0.82,2.34] kg; p < 0.01; I2  = 64.0%) unlike the PCOS subgroup with BMI < 25 kg/m2 (-0.45 [-1.94,1.05] kg; p = 0.53; I2  = 69.5%). Appendicular lean mass and muscle strength data were contradictory and described narratively, as meta-analyses were impossible. Women with PCOS have higher total and trunk lean tissue mass attributed to overweight/obesity, unlike hyperandrogenism or insulin resistance.

A rodent model of human dose-equivalent progestin-only implantable contraception.

BACKGROUND: Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. METHODS: Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30µg/d, medium-0.17µg/d, low-0.09µg/d, placebo-0.00µg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. RESULTS: Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. CONCLUSION: Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

Effects of Dietary Glycemic Index and Glycemic Load on Cardiometabolic and Reproductive Profiles in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Women with polycystic ovary syndrome (PCOS) exhibit cardiometabolic (e.g., insulin resistance) and associated reproductive disruptions. Lifestyle modification (e.g., diet) is recommended as the first-line therapy to manage PCOS; however, a favorable dietary regimen remains unclear beyond energy restriction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to summarize evidence on impacts of dietary glycemic index (GI) or glycemic load (GL) on cardiometabolic and reproductive profiles to update the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Cochrane, Web of Science, and Scopus were searched through 30 October 2019, and confirmed on 25 March 2020, to identify RCTs (≥8 wk) comparing the effects of diets with lower (LGI/LGL) and higher (HGI/HGL) GI/GL on glucoregulatory outcomes, lipid profile, anthropometrics, and androgen status in PCOS. The primary outcome was HOMA-IR. Data were pooled by random-effects models and expressed as weighted mean differences and 95% CIs. The risk of bias was assessed by the Cochrane tool. Ten RCTs (n = 403) were eligible. Eight evaluated LGI and 2 LGL diets. LGI diets decreased HOMA-IR (-0.78; -1.20, -0.37; I2 = 86.6%), fasting insulin (-2.39; -4.78, 0.00 µIU/mL; I2 = 76.8%), total cholesterol (-11.13; -18.23, -4.04 mg/dL; I2 = 0.0%), LDL cholesterol (-6.27; -12.01, -0.53 mg/dL; I2 = 0.0%), triglycerides (-14.85; -28.75, -0.95 mg/dL; I2 = 31.0%), waist circumference (-2.81; -4.40, -1.23 cm; I2 = 53.9%), and total testosterone (-0.21; -0.32, -0.09 nmol/L; I2 = 8.6%) compared with HGI diets (all: P ≤ 0.05) without affecting fasting glucose, HDL cholesterol, weight, or free androgen index (all: P ≥ 0.07). Some results were contradictory and only described narratively for 2 RCTs that evaluated LGL diets, since inclusion in meta-analyses was not possible. LGI diets improved glucoregulatory outcomes (HOMA-IR, insulin), lipid profiles, abdominal adiposity, and androgen status, conceivably supporting their inclusion for dietary management of PCOS. Further RCTs should confirm these observations and address whether LGI diets improve more patient-pressing complications, including ovulatory cyclicity, infertility, and cardiovascular disease risk in this high-risk population. This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42020175300.

Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation.

Elucidation of multiple waves of antral ovarian follicular development during the menstrual cycle has challenged traditional concepts of female reproductive physiology and foundations of assisted reproductive therapies. Approximately two-thirds of women develop two follicle waves throughout an interovulatory interval and the remainder exhibit three waves of follicle development. Major and minor waves of follicle development have been observed. Major waves are those in which a dominant follicle develops; dominant follicles either regress or ovulate. In minor waves, physiologic selection of a dominant follicle is not manifest. Knowledge of waves of antral follicular development has led to the global adoption of novel ovarian stimulation strategies in which stimulation can be initiated at various times throughout the cycle. Random-start and luteal-phase ovarian stimulation regimens have had important clinical applications for women requiring urgent oocyte or embryo cryopreservation for fertility preservation prior to chemotherapy. Ovarian stimulation twice in the same cycle, referred to as double stimulation, may be used to optimize clinical outcomes in women with a poor ovarian response to stimulation as well as in those requiring fertility preservation before chemotherapy.

A randomized controlled trial of a lifestyle intervention with longitudinal follow-up on ovarian dysmorphology in women with polycystic ovary syndrome.

OBJECTIVE: Effects of lifestyle modification on reproductive function in polycystic ovary syndrome (PCOS) remain poorly elucidated. We compared the effects of a pulse-based diet (lentils, beans, split peas and chickpeas) with Therapeutic Lifestyle Changes (TLC) diet on ultrasonographic markers of ovarian morphology, hyperandrogenism and menstrual irregularity in PCOS. DESIGN: Randomized controlled trial. PATIENTS: Women with PCOS (18-35 years). MEASUREMENTS: Thirty women randomized to the pulse-based and 31 to TLC groups completed a 16-week intervention without energy restriction. Groups performed aerobic exercise (minimum of 5 days/wk; 45 minutes/d) and received health counselling (monthly) and longitudinal follow-up. Follicle numbers per ovary (FNPO, 2-9 mm), ovarian volume (OV), free androgen index (FAI) and menstrual cycle length were measured pre- and postintervention. RESULTS: Follicle numbers per ovary (mean change ± SD, -10 ± 15), OV (-2.7 ± 4.8 mL), FAI (-3 ± 2) and menstrual cycle length (-13 ± 47 days) decreased over time in both groups (All: P < .01), without group-by-time interactions (All: P ≥ .13). Attrition rate was 33.7% and comparable between groups (P = .94). Adherence to diet intervention negatively correlated with changes in FNPO (r=-0.54), OV (r=-0.35) and FAI (r = -.29) in pooled groups (All: P ≤ .04). Groups maintained reduced OV, FNPO, FAI and menstrual cycles 6 months postintervention; however, decreased FNPO and FAI at 16 weeks tended to revert to baseline levels 12 months postintervention in both groups (All: P ≤ .05). CONCLUSIONS: Both interventions improved ovarian dysmorphology, hyperandrogenism and menstrual irregularity in PCOS, and no diet appeared to be superior at improving reproductive outcomes. Our observations highlight the importance of longitudinal surveillance for sustainable adherence to newly adopted healthy lifestyle behaviours and reproductive health in PCOS (ClinicalTrials.gov identifier, NCT01288638).

A pulse-based diet and the Therapeutic Lifestyle Changes diet in combination with health counseling and exercise improve health-related quality of life in women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial.

Objective: A favorable dietary composition to increase health-related quality of life (HRQoL) in PCOS remains unclear. We compared changes in HRQoL of women with PCOS who participated in a low-glycemic-index pulse-based (lentils, beans, split peas, and chickpeas) or the Therapeutic Lifestyle Changes (TLC) diet intervention.Methods: Thirty women in the pulse-based and 31 in the TLC groups (18-35 years) completed a 16-week intervention without energy-restriction. Groups participated in health counseling (monthly) and aerobic exercise (5 days/week; 45 minutes/day).Results: Fifty-five (90.2%) women completed a PCOS-specific HRQoL survey. Greatest mean increases in time-effects occurred in the domains of healthy eating, PCOS knowledge, active living, healthcare satisfaction, feelings and experiences about intervention, and health concerns, respectively (p ≤ 0.02), without group-by-time interactions (p ≥ 0.13). Decreased weight (r = -0.35) and homeostatic model assessment of insulin resistance (r = -0.18) correlated with increased scores of PCOS knowledge; adherence to intervention correlated with increased scores of active living (r = 0.39) and healthy eating (r = 0.53; p ≤ 0.03).Conclusions: Both interventions improved HRQoL scores in women with PCOS without prescribed energy-restriction. Our observations add novel insights into current evidence and elucidate the need for future psychological research to target lifestyle modifications for improving HRQoL and unique psychological complications of PCOS in this high-risk population (CinicalTrials.gov identifier:NCT01288638).

Dysglycemia, Not Altered Sex Steroid Hormones, Affects Cognitive Function in Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex endocrine condition characterized by multiple reproductive and metabolic abnormalities. Because individual reproductive and metabolic abnormalities modulate working memory in the general population, there is growing interest in whether cognitive function is dually and negatively affected in PCOS. OBJECTIVE: To examine the association of reproductive and metabolic features with cognitive function in women with and without PCOS. DESIGN: An observational, cross-sectional study was conducted at an academic clinical research center in North America between 2006 and 2009. Common tests of working memory (i.e., manual dexterity, perceptual speed, and visuospatial ability) were performed by women with PCOS (n = 40) and control subjects (n = 40). Markers of sex steroid hormones, ovulatory function, and cardiometabolic health were also assessed. RESULTS: Reduced visuospatial ability was observed in women with PCOS compared with control subjects (P < 0.01). Reduced visuospatial ability was linked to higher levels of hemoglobin A1c in the entire study cohort, independent of body mass index or PCOS status. No associations were observed between visuospatial ability and reproductive features, after controlling for confounding variables. CONCLUSION: Our findings support a role for glycemic control, and not PCOS per se, in cognitive dysfunction in women of reproductive age. Additional studies are needed to understand the short- and long-term effects of dysglycemia on brain health in women with PCOS, given their increased propensity for metabolic comorbidities, compared with control subjects.

Impact of right-left differences in ovarian morphology on the ultrasound diagnosis of polycystic ovary syndrome.

OBJECTIVE: To assess right-left differences in ultrasonographic markers of ovarian morphology and determine the impact on the diagnosis of polycystic ovarian morphology (PCOM). DESIGN: A cross-sectional study of data collected from 2006 to 2018. SETTING: Academic clinical research centers. PATIENT(S): Women with polycystic ovary syndrome (PCOS; n = 87) and controls (n = 67). INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Follicle number per ovary (FNPO), follicle number per cross-section (FNPS), and ovarian volume (OV) were assessed in both ovaries using transvaginal ultrasonography. PCOM was identified based on recent international consensus guidelines or proposed diagnostic thresholds. RESULT(S): Overall, mean right-left differences were two follicles for FNPO, one follicle for FNPS, and 2 mL for OV. FNPO showed the strongest correlation between ovaries. Its assessment in a single ovary did not impact the diagnosis of PCOM in women with PCOS. However, there were differences in the probability of unilateral versus bilateral PCOM based on FNPS and OV in both groups. CONCLUSION(S): FNPO is the most reliable unilateral marker of PCOM in light of right-left differences in ovarian morphology. Use of FNPS or OV to define PCOM is discouraged when only one ovary is visualized.

Comprehensive Evaluation of Type 2 Diabetes and Cardiovascular Disease Risk Profiles in Reproductive-Age Women with Polycystic Ovary Syndrome: A Large Canadian Cohort.

OBJECTIVE: This study compared the prevalence of metabolic syndrome (MetS) and characterized type 2 diabetes (DM2) and cardiovascular disease (CVD) risk profiles between Canadian women with polycystic ovary syndrome (PCOS) and healthy women recruited from the general population. Furthermore, within the PCOS cohort, the study contrasted the CVD and DM2 risk profiles of women with or without MetS. METHODS: Measures of MetS (International Diabetes Federation; National Heart, Lung, and Blood Institute; and the American Heart Association definition), DM2 (Diabetes Canada Clinical Guidelines), and CVD risk factors (Androgen Excess and Polycystic Ovary Syndrome Society statement) were evaluated for 237 women with PCOS (Androgen Excess and PCOS Society definitions) and 42 controls (aged 18-36) in a prospective observational study (Canadian Task Force Classification II-2). RESULTS: The prevalence of MetS was 29.5% in the PCOS group, which was approximately six-fold higher than age-matched controls (P < 0.001). Women with PCOS exhibited higher glucose abnormality, acanthosis nigricans, total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C), and lower sex hormone-binding globulin concentrations when compared with controls after accounting for differences in the BMI (P < 0.01). Further, women with PCOS and MetS exhibited exacerbated insulin and glucose responses to a 75-g oral glucose tolerance test and greater acanthosis nigricans, hirsutism, TC/HDL-C, TC, and sex hormone-binding globulin concentrations compared with their BMI-adjusted counterparts without MetS (P < 0.05). CONCLUSION: Canadian reproductive-age women with PCOS have a high prevalence of MetS and exhibit adverse cardiometabolic risk factors that warrant early screening and regular monitoring across their reproductive lifespan.

A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet in Combination with Exercise and Health Counselling on the Cardio-Metabolic Risk Profile in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

We compared the effects of a low-glycemic index pulse-based diet, containing lentils, beans, split peas, and chickpeas, to the Therapeutic Lifestyle Changes (TLC) diet on cardio-metabolic measures in women with polycystic ovary syndrome (PCOS). Ninety-five women (18⁻35 years) enrolled in a 16-week intervention; 30 women in the pulse-based and 31 in the TLC groups completed the study. Women participated in aerobic exercise training (minimum 5 days/week for 45 min/day) and were counselled (monthly) about PCOS and lifestyle modification. Women underwent longitudinal follow-up post-intervention. The pulse-based group had a greater reduction in total area under the curve for insulin response to a 75-g oral glucose tolerance test (mean change ± SD: -121.0 ± 229.9 vs. -27.4 ± 110.2 µIU/mL × min; p = 0.05); diastolic blood pressure (-3.6 ± 6.7 vs. -0.2 ± 6.7 mmHg, p = 0.05); triglyceride (-0.2 ± 0.6 vs. 0.0 ± 0.5 mmol/L, p = 0.04); low-density lipoprotein cholesterol (-0.2 ± 0.4 vs. -0.1 ± 0.4 mmol/L, p = 0.05); total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C; -0.4 ± 0.4 vs. 0.1 ± 0.4, p < 0.001); and a greater increase in HDL-C (0.1 ± 0.2 vs. -0.1 ± 0.2 mmol/L, p < 0.01) than the TLC group. Decreased TC/HDL-C (p = 0.02) at six-month and increased HDL-C and decreased TC/HDL-C (p ≤ 0.02) at 12-month post-intervention were maintained in the pulse-based group. A pulse-based diet may be more effective than the TLC diet at improving cardio-metabolic disease risk factors in women with PCOS. TRIAL REGISTRATION: CinicalTrials.gov identifier, NCT01288638.

Women With Polycystic Ovary Syndrome Have Comparable Hip Bone Geometry to Age-Matched Control Women.

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women of reproductive age manifesting with polycystic ovaries, menstrual irregularities, hyperandrogenism, hirsutism, and insulin resistance. The oligomenorrhea and amenorrhea characteristic to PCOS are associated with low bone mineral density (BMD); conversely, the hyperandrogenism and hyperinsulinemia may elicit a protective effect on BMD. As bone geometric properties provide additional information about bone strength, the objective of this study was to compare measures of hip geometry in women with PCOS to a healthy female population. Using dual-energy X-ray absorptiometry, BMD and measures of hip geometry were determined in women with PCOS (n = 60) and healthy controls (n = 60) aged 18-35 years. Clinical biochemical measures were also determined in women with PCOS. Measures of hip geometry, including cross-sectional area, cross-sectional moment of inertia, subperiosteal width (SPW), and section modulus, were similar between groups following correction for body mass index (BMI) (all p > 0.05) with intertrochanter SPW significantly lower in women with PCOS (p < 0.05). BMI-corrected whole body BMD as well as the lumbar spine and regions of proximal femur were also comparable between groups. In women with PCOS, BMI-corrected correlations were found between insulin and femoral shaft SPW (r = 0.322, p < 0.05), glucose and femoral neck (r = 0.301, p < 0.05), and trochanter BMD (0.348, p < 0.05), as well as between testosterone and femoral neck BMD (0.376, p < 0.05) and narrow neck cross-sectional area (0.306, p < 0.05). This study demonstrates that women with PCOS may have compromised intertrochanter SPW while oligomenorrhea appears to have no detrimental effect on bone density or geometry in women with PCOS.

The role of a pulse-based diet on infertility measures and metabolic syndrome risk: protocol of a randomized clinical trial in women with polycystic ovary syndrome.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is an endocrine disorder in women of reproductive age with an estimated prevalence of 5-20% of premenopausal women. The clinical symptoms common to PCOS include menstrual dysfunction, hyperandrogenemia, hirsutism, polycystic ovaries, insulin resistance, and hyperinsulinemia. Women with PCOS are at an increased risk of infertility, obesity and type 2 diabetes mellitus. Insulin resistance and hyperinsulinemia are believed to be key contributing factors to the pathogenesis of PCOS; excessive amounts of insulin are directly associated with the increased ovarian production of androgens and metabolic features of PCOS. Pulse-based diets (e.g., beans, chickpeas) are associated with improved glycemic control and have insulin lowering effects. The purpose of this study is to determine whether a pulse-based diet is more effective than the diet recommended by the National Cholesterol Education Program. The primary outcomes of this study are disease measures related to PCOS, with secondary outcomes including measures related to metabolic syndrome. METHODS: Women with symptoms of PCOS will be recruited for the study and a diagnosis of PCOS will be determined by an obstetrician-gynecologist. Women with PCOS will be randomly assigned to receive either a pulse-based diet or the National Cholesterol Education Program therapeutic lifestyle changes (TLC) diet for 16 weeks while participating in an aerobic exercise program. One hundred participants will be required (drop-out rate of 32%) for recruitment to provide 80% power for detecting a significant difference in fasting glucose (p < 0.05). Measures related to infertility, metabolic syndrome, quality of life, dietary intake and physical activity will be assessed pre- and post-intervention with follow up assessment at 6- and 12-months post-intervention. DISCUSSION: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age and there is currently no recommended diet for this population of women. The multidisciplinary nature of this study, including determination of measures related to metabolic syndrome, infertility and physical activity provide a comprehensive assessment of any benefits associated with a pulse-based diet in women with PCOS. The results of this study will help in providing evidence-based recommendations for the optimum diet to reduce symptoms associated with PCOS. TRIAL REGISTRATION: NCT01288638. Trial registered January 13, 2011.

Cycle-phase dependent associations between CRP, leptin, and reproductive hormones in an urban, Canadian sample.

OBJECTIVES: To assess the relationships among reproductive hormones, follicular development, inflammation, and adiposity in a sample of urban, Canadian women. MATERIALS AND METHODS: Participants (n = 41) had blood collected every 3 days through one interovulatory interval (IOI) to measure estradiol, progesterone, LH, FSH, leptin, and C-reactive protein (CRP). Participants underwent daily transvaginal ultrasound examinations during the IOI to quantify all follicles > 2 mm. CRP and leptin tertiles were used to compare conditions of high and low inflammatory processes and adiposity, respectively. RESULTS: Luteal phase estradiol, luteal phase LH, and follicular phase progesterone were lower among individuals in the highest CRP tertile (adjusted r(2) = 0.63, 0.70, 0.76, respectively). Luteal and follicular phase follicle diameter was greatest in the high CRP tertile (adjusted r(2) = 0.68, 0.71). Follicular phase progesterone was lowest among individuals in the highest leptin tertile, and follicular phase FSH was lowest among individuals in the lowest leptin tertile (adjusted r(2) = 0.54, 0.45). Luteal phase follicle diameter was highest among those in the moderate leptin tertile (adjusted r(2) = 0.49). DISCUSSION: This study is a first comprehensive assessment of the relationship between multiple ovarian function components and inflammatory biomarkers. The results are interpreted to mean that inflammatory and energetic stressors produce differential effects depending on population, adiposity, and cycle phase. Am J Phys Anthropol 160:389-396, 2016. © 2016 Wiley Periodicals, Inc.

The associations of exposure to combined hormonal contraceptive use on bone mineral content and areal bone mineral density accrual from adolescence to young adulthood: A longitudinal study.

BACKGROUND: The association of long term combined hormone based contraceptives (CHC) use on bone mineral content (BMC) and areal bone mineral density (aBMD) development remains controversial, as it appears that the relationship may be age-dependent. The purpose of this study was to investigate the long-term associations of CHC exposure on the accrual of bone parameters from adolescence into young-adulthood. METHODS: 110 women (67 exposed to CHC) were drawn from the Pediatric Bone Mineral Accrual Study (PBMAS). Serial measures of total body (TB), lumbar spine (LS) and femoral neck (FN) BMC and aBMD were assessed by DXA (a total of 950 scans) and aligned by biological age (BA, years from peak height velocity [PHV]). Multilevel random effects models were constructed to assess the time dependent associations between annual CHC exposure and the development of bone parameters. RESULTS: After BA, height, lean tissue mass, fat mass, calcium and vitamin D intake, and physical activity were controlled, it was observed that those individuals exposed to CHC 6-years post PHV developed significantly less (-0.00986 ± 0.00422 g/cm2) TB aBMD than their non CHC exposed peers. Additionally, there were significant BA by CHC exposure interactions, where CHC exposure 6-years or more post PHV resulted in developing less TB BMC (-4.94 ± 2.41 g), LS BMC (-0.29 ± 0.11 g) and LS aBMD (-0.00307 ± 0.00109 g/cm2). One year after the attainment of PHV, CHC users were predicted to have 1.2% more TB BMC, 3.8% more LS BMC and 1.7% more LS aBMD than non-users. At 9-years post PHV the predicted differences showed that CHC users had 0.9% less TB BMC and 2.7% less LS BMC and 1.6% less LS BMD than those not exposed to CHC. CONCLUSIONS: CHC may not hinder the development of BMC or aBMD during adolescence; however, exposure 6-years or more after PHV may be detrimental.

Ultrasound features of polycystic ovaries relate to degree of reproductive and metabolic disturbance in polycystic ovary syndrome.

OBJECTIVE: To reexamine associations between polycystic ovarian morphology (PCOM) and degree of symptomatology in polycystic ovary syndrome (PCOS) using a well-defined PCOS population, newer ultrasound technology, and reliable offline assessments of sonographic parameters. DESIGN: Cross-sectional observational study. SETTING: Academic hospital and clinical research unit. PATIENT(S): Forty-nine women with PCOS as defined by hyperandrogenism and oligoamenorrhea. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of follicles per follicle size category, antral follicle count (AFC), ovarian volume (OV), follicle distribution pattern, stromal area, ovarian area, stromal to ovarian area ratio (S/A) and stromal echogenicity index (SI), total (TT), androstenedione, LH, FSH, cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, C-reactive protein, glucose, insulin, and hemoglobin A1C, menstrual cycle length, hirsutism score, body mass index (BMI), waist:hip ratio, and blood pressure. RESULT(S): AFC, but not OV, was positively associated with TT (ρ = .610), androstenedione (ρ = .490), and LH:FSH (ρ = .402). SI was positively associated with androgen markers and LH:FSH, while S/A was negatively associated with these variables. Follicles ≤4 mm were negatively associated with various metabolic markers, whereas larger follicles (5-8 mm) showed positive associations. Stromal markers were not associated with cardiometabolic measures. LH:FSH best predicted follicles ≤4 mm, and BMI predicted 5- to 9-mm follicles. Dominant follicles ≥10 mm were best predicted by age. CONCLUSION(S): AFC, and not OV, reflected the severity of reproductive dysfunction in PCOS. Associations among different sized follicles were consistent with recruitable sized follicles, which reflects the severity of metabolic dysfunction in PCOS.

Recombinant human luteinizing hormone to trigger ovulation: randomized, controlled, dose-finding pilot study in ovulation induction.

OBJECTIVE: To evaluate recombinant human luteinizing hormone (r-hLH) versus urine-derived human chorionic gonadotropin (u-hCG) to trigger ovulation in women (aged 20-40 years) with WHO Group II anovulatory infertility undergoing ovulation induction (OI) with recombinant human follicle-stimulating hormone (r-hFSH) (150 IU/day starting dose). STUDY DESIGN: For this Phase II, open-label, dose-finding pilot study, patients were randomized to doses of 825, 2,750, 5,500, 11,000, or 22,000 IU r-hLH or u-hCG (5,000 IU). Primary endpoints were ovulation and ratio of ruptured follicles/follicle > or = 15 mm (day of r-hLH/ u-hCG administration). Secondary endpoints included monofollicular ovulation and clinical pregnancy rates. RESULTS: All 67 randomized patients completed treatment. All patients in the r-hLH 2,750 (13/13), 5,500 (12/ 12), 11,000 IU (13/13), and u-hCG 5,000 IU (12/ 12) groups ovulated; 3/5 patients in the r-hLH 825 IU and 2/12 in the r-hLH 22,000 IU group failed to ovulate (p = 0.105 between evaluable groups). The mean ratio of ruptured follicles/ follicle > or = 15 mm was 1.1 (p = 0.675 between groups). The monofollicular ovulation rate was 15/60 (25%). Two cases of ovarian hyperstimulation syndrome were reported. CONCLUSION: This open-label, pilot study (conducted in 1999-2001) suggests that the minimal effective dose of r-hLH to trigger ovulation in women with WHO Group II anovulatory infertility undergoing OI with r-hFSH (150 IU starting dose) was 2,750 IU.