Smoking in infertile women with polycystic ovary syndrome: baseline validation of self-report and effects on phenotype.

STUDY QUESTION: Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking? SUMMARY ANSWER: Self-report of smoking in infertile women with PCOS is accurate (based on serum cotinine levels) and smoking is unlikely to change over time with infertility treatment. WHAT IS KNOWN ALREADY: Women with PCOS have high rates of smoking and it is associated with worse insulin resistance and metabolic dysfunction. STUDY DESIGN, SIZE, DURATION: Secondary study of smoking history from a large randomized controlled trial of infertility treatments in women with PCOS (N = 626) including a nested case-control study (N = 148) of serum cotinine levels within this cohort to validate self-report of smoking. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS, age 18-40, seeking fertility who participated in a multi-center clinical trial testing first-line ovulation induction agents conducted at academic health centers in the USA. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, self-report of smoking in the nested case-control study agreed well with smoking status as determined by measure of serum cotinine levels, at 90% or better for each of the groups at baseline (98% of never smokers had cotinine levels <15 ng/ml compared with 90% of past smokers and 6% of current smokers). There were minor changes in smoking status as determined by serum cotinine levels over time, with the greatest change found in the smoking groups (past or current smokers). In the larger cohort, hirsutism scores at baseline were lower in the never smokers compared with past smokers. Total testosterone levels at baseline were also lower in the never smokers compared with current smokers. At end of study follow-up insulin levels and homeostatic index of insulin resistance increased in the current smokers (P < 0.01 for both) compared with baseline and with non-smokers. The chance for ovulation was not associated with smoking status, but live birth rates were increased (non-significantly) in never or past smokers. LIMITATIONS, REASONS FOR CAUTION: The limitations include the selection bias involved in our nested case-control study, the possibility of misclassifying exposure to second hand smoke as smoking and our failure to capture self-reported changes in smoking status after enrollment in the trial. WIDER IMPLICATIONS OF THE FINDINGS: Because self-report of smoking is accurate, further testing of smoking status is not necessary in women with PCOS. Because smoking status is unlikely to change during infertility treatment, extra attention should be focused on smoking cessation in current or recent smokers who seek or who are receiving infertility treatment. STUDY FUNDING/COMPETING INTERESTS: Sponsored by the Eugene Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov numbers, NCT00068861 and NCT00719186.

A Framework for Diversifying Obstetrics and Gynecology Training Programs.

There is an urgent need to diversify the physician workforce in obstetrics and gynecology to serve a diverse patient population and mitigate disparities in care. There is a paucity of data on how to improve recruitment of individuals from underrepresented minoritized groups to the field of obstetrics and gynecology. This article outlines important steps for sharing the department's commitment to diversity, equity, and inclusion; addresses ways to attract a diverse applicant pool; and reviews the importance of and need to perform a holistic review of applicants. This commentary also shares some approaches to support faculty and trainees that may lead to sustained increases in diversity. Using this framework, the authors successfully increased the diversity of their obstetrics and gynecology residency program.

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.

BACKGROUND: The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. METHODS: We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. RESULTS: The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. CONCLUSIONS: Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov].).

Conception rates and contraceptive use after bariatric surgery among women with infertility: Evidence from a prospective multicenter cohort study.

BACKGROUND: Lack of prospective trials have resulted in a dearth of information regarding postbariatric surgery conception rates in women with a preoperative history of infertility. OBJECTIVE: To examine associations between preoperative history of infertility and postbariatric surgery conception. SETTING: A multicenter cohort study at 10 United States hospitals (2006-2009). METHODS: Participants completed a preoperative reproductive health questionnaire, with annual postoperative assessments for up to 7 years until January 2015. This report was restricted to women 18- to 44-years old with no history of menopause, hysterectomy, or hormone replacement therapy. The primary outcomes were postoperative (0 to <90 mo) conception rate, early conception rate (0 < 18 mo), and postoperative unprotected intercourse with a male partner while not trying to conceive. RESULTS: Of 740 eligible women, 650 (87.8%) provided required responses. Median interquartile range (IQR) preoperative age was 34 (30-39) years and follow-up was 6.5 (5.9-7.0) years. Nulliparous women with a preoperative history of infertility represented 8.0% (52/650) of the total cohort, 63.5% (33/52) of whom had never conceived. Compared with women without this history, these women had a higher postoperative conception rate (121.2 [95% confidence interval (CI), 102.3-143.5]/1000 versus 47.0 [95%CI, 34.2-62.9]/1000 woman-yr; P < .001), early conception rate (115.4 [95%CI, 96.1-138.5]/1000 versus 33.9 [95%CI, 23.6-47.1]/1,000 woman-yr; P < .01), and a higher risk of unprotected intercourse (ARR 1.48 [95% CI, 1.14-1.90], P = 0.003). CONCLUSION: After bariatric surgery, preoperative history of infertility and nulliparity was associated higher conception rates and unprotected intercourse.

Ovulatory response to treatment of polycystic ovary syndrome is associated with a polymorphism in the STK11 gene.

CONTEXT: Clomiphene and insulin sensitizers such as metformin are used to induce ovulation in polycystic ovary syndrome (PCOS), but the ovulatory response is variable, and the causes of this variation are poorly understood. OBJECTIVE: Our objective was to identify predictive genetic polymorphisms and other determinants of ovulatory response. DESIGN: This was a substudy of a multicenter randomized clinical trial. SETTING: This study was performed at academic medical centers and their affiliates. PARTICIPANTS: A total of 312 women with PCOS were included in the study. MAIN OUTCOME MEASURES: Historical, biometric, biochemical, and genetic parameters were performed. RESULTS: We found that the C allele of a single nucleotide polymorphism in the STK11 gene (expressed in liver; also known as LKB1) was associated with a significantly decreased chance of ovulation in PCOS women treated with metformin. In an analysis of ovulation per cycle, the adjusted odds ratio (OR) comparing the C/C genotype to the G/G genotype was 0.30 [95% confidence interval (CI) 0.14, 0.66], and the OR for the C/G genotype vs. the G/G genotype was also 0.30 (95% CI 0.14, 0.66). In an analysis of metformin-treated subjects, we found that the percentage of women who ovulated increased with the number of G alleles present: 48% (10 of 21) of C/C women, 67% (32 of 48) of C/G women, and 79% (15 of 19) of G/G women ovulated. We also found that increased frequency of ovulation was associated with lower body mass index (BMI) [adjusted OR of 2.36 (95% CI 1.65, 3.36) and 2.05 (95% CI 1.46, 2.88), respectively, for comparisons of BMI less than 30 vs. BMI equal to or more than 35, BMI 30-34 vs. BMI equal to or more than 35, in the analysis of ovulation per cycle], a lower free androgen index (FAI) [adjusted OR of 1.59 (95% CI 1.17, 2.18) for FAI<10 vs. FAI>or=10], and a shorter duration of attempting conception [adjusted OR of 1.63 (95% CI 1.20, 2.21) for<1.5 vs.>or=1.5 yr]. CONCLUSIONS: We have demonstrated that a polymorphism in STK11, a kinase gene expressed in liver and implicated in metformin action, is associated with ovulatory response to treatment with metformin alone in a prospective randomized trial. The interaction with the effects of changes in modifiable factors (e.g. BMI or FAI) requires further study.

Introduction of an obstetric-specific medical emergency team for obstetric crises: implementation and experience.

OBJECTIVE: We describe the implementation and experience with adding an obstetric-specific medical emergency team (called Condition O for obstetric crisis) to an existing rapid response system at Magee-Womens Hospital. STUDY DESIGN: In response to deficits identified during patient safety review of adverse obstetric events in 2004 and 2005, the hospital administration decided to add a crisis team with expertise specifically designed for maternal and/or fetal crises. RESULTS: During the first 6 months, staff rarely called Condition O (14 per 10,000 obstetric admissions). After reeducation efforts, use of Condition O increased to 62 per 10,000 obstetric admissions during 2006. CONCLUSION: We outline our hospital's experience with implementation, efforts to address low utilization, and 1.5 years of Condition O event data. Condition O is a work in progress. In light of this, we discuss the challenges of measuring its patient safety outcome, considerations for team size and composition, and our efforts to determine an optimal Condition O rate.

Contraception and Conception After Bariatric Surgery.

OBJECTIVE: To examine contraceptive practices and conception rates after bariatric surgery. METHODS: The Longitudinal Assessment of Bariatric Surgery-2 is a multicenter, prospective cohort study of adults undergoing first-time bariatric surgery as part of routine clinical care at 10 U.S. hospitals. Recruitment occurred between 2005 and 2009. Participants completed preoperative and annual postsurgical assessments for up to 7 years until January 2015. This report was restricted to women 18-44 years old with no history of menopause, hysterectomy, or estrogen and progesterone therapy. Primary outcomes were self-reported contraceptive practices, overall conception rate, and early (less than 18 months) postsurgical conception. Contraceptive practice (no intercourse, protected intercourse, unprotected intercourse, or tried to conceive) was classified based on the preceding year. Conception rates were determined from self-reported pregnancies. RESULTS: Of 740 eligible women, 710 (95.9%) completed follow-up assessment(s). Median (interquartile range) preoperative age was 34 (30-39) years. In the first postsurgical year, 12.7% (95% CI 9.4-16.0) of women had no intercourse, 40.5% (95% CI 35.6-45.4) had protected intercourse only, 41.5% (95% CI 36.4-46.6) had unprotected intercourse while not trying to conceive, and 4.3% (95% CI 2.4-6.3) tried to conceive. The prevalence of the first three groups did not significantly differ across the 7 years of follow-up (P for all >.05); however, more women tried to conceive in the second year (13.1%, 95% CI 9.3-17.0; P<.001). The conception rate was 53.8 (95% CI 40.0-71.1) per 1,000 woman-years across follow-up (median [interquartile range] 6.5 [5.9-7.0] years); 42.3 (95% CI 30.2-57.6) per 1,000 woman-years in the 18 months after surgery. Age (adjusted relative risk 0.41 [95% CI 0.19-0.89] per 10 years, P=.03), being married or living as married (adjusted relative risk 4.76 [95% CI 2.02-11.21], P<.001), and rating future pregnancy as important preoperatively (adjusted relative risk 8.50 [95% CI 2.92-24.75], P<.001) were associated with early conception. CONCLUSIONS: Postsurgical contraceptive use and conception rates do not reflect recommendations for an 18-month delay in conception after bariatric surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00465829.

Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial.

CONTEXT: Experimental evidence supports a relevance of vitamin D (VitD) for reproduction; however, data in humans are sparse and inconsistent. OBJECTIVE: To assess the relationship of VitD status with ovulation induction (OI) outcomes in women with polycystic ovary syndrome (PCOS). DESIGN: A retrospective cohort. SETTING: Secondary analysis of randomized controlled trial data. PARTICIPANTS: Participants in the Pregnancy in PCOS I (PPCOS I) randomized controlled trial (n = 540) met the National Institutes of Health diagnostic criteria for PCOS. INTERVENTIONS: Serum 25OHD levels were measured in stored sera. MAIN OUTCOME MEASURES: Primary, live birth (LB); secondary, ovulation and pregnancy loss after OI. RESULTS: Likelihood for LB was reduced by 44% for women if the 25OHD level was < 30 ng/mL (<75 nmol/L; odds ratio [OR], 0.58 [0.35-0.92]). Progressive improvement in the odds for LB was noted at thresholds of ≥38 ng/mL (≥95 nmol/L; OR, 1.42 [1.08-1.8]), ≥40 ng/mL (≥100 nmol/L; OR, 1.51 [1.05-2.17]), and ≥45 ng/mL (≥112.5 nmol/L; OR, 4.46 [1.27-15.72]). On adjusted analyses, VitD status was an independent predictor of LB and ovulation after OI. CONCLUSIONS: In women with PCOS, serum 25OHD was an independent predictor of measures of reproductive success after OI. Our data identify reproductive thresholds for serum 25OHD that are higher than recommended for the nonpregnant population.

Focused assessment of surgical performance: difficulty with faculty compliance.

OBJECTIVE: This study evaluated faculty compliance in the use of the global surgical rating scale of the Objective Structured Assessment of Technical Skills to rate resident surgical performance after every endoscopic procedure. STUDY DESIGN: For this prospective cohort study, 4 faculty members in the Minimally Invasive Gynecology Surgery Program were asked to rate resident surgical performance using the Objective Structured Assessment of Technical Skills instrument after every case. Faculty compliance was analyzed with respect to the influence of the resident or surgical case characteristics. Faculty and residents completed surveys about the value of the case-by-case ratings. RESULTS: Faculty members used the Objective Structured Assessment of Technical Skills instrument 36% of the time (range, 26%-60%). Faculty member compliance did not vary according to resident or surgical case characteristics. Faculty members did not think the forms had much impact on whether they gave feedback. Residents thought the opportunity to read their ratings was helpful. CONCLUSION: Faculty member compliance with case-by-case surgical performance evaluation of the residents was low.

Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome.

OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory with progestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001). CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS. LEVEL OF EVIDENCE: II.

Altering hirsutism through ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: Many women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate, metformin, or both would have greater improvement in hirsutism compared with those who did not ovulate. METHODS: This is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n=505 [80.7%]) from the Pregnancy in Polycystic Ovary Syndrome I study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment. RESULTS: There was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, P=.024; metformin, P=.005; combination, P<.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (P=.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation. CONCLUSION: In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to six cycles does not alter hirsutism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861. LEVEL OF EVIDENCE: II.

Metformin and/or clomiphene do not adversely affect liver or renal function in women with polycystic ovary syndrome.

CONTEXT: Nonalcoholic fatty liver disease is common to insulin-resistant states such as polycystic ovary syndrome (PCOS). Metformin (MET) is often used to treat PCOS but information is limited as to its effects on liver function. OBJECTIVE: We sought to determine the effects of MET on serum hepatic parameters in PCOS patients. DESIGN: This was a secondary analysis of a randomized, doubled-blind trial from 2002-2004. SETTING: This multi-center clinical trial was conducted in academic centers. PATIENTS: Six hundred twenty-six infertile women with PCOS with serum liver function parameters less than twice the upper limit of normal were included. INTERVENTIONS: Clomiphene citrate (n = 209), MET (n = 208), or combined (n = 209) were given for up to 6 months. MAIN OUTCOME MEASURE: The percent change from baseline in renal and liver function between- and within-treatment arms was assessed. RESULTS: Renal function improved in all treatment arms with significant decreases in serum blood urea nitrogen levels (range, -14.7 to -21.3%) as well as creatinine (-4.2 to -6.9%). There were similar decreases in liver transaminase levels in the clomiphene citrate and combined arms (-10% in bilirubin, -9 to -11% in transaminases) without significant changes in the MET arm. When categorizing baseline bilirubin, aspartate aminotransferase, and alanine aminotransferase into tertiles, there were significant within-treatment arm differences between the tertiles with the highest tertile having the largest decrease from baseline regardless of treatment arm. CONCLUSION: Women with PCOS can safely use metformin and clomiphene even in the setting of mildly abnormal liver function parameters, and both result in improved renal function.

Reproductive health of women electing bariatric surgery.

OBJECTIVE: To describe the reproductive health history and characteristics of women having bariatric surgery and to determine whether this differs by age of onset of obesity. DESIGN: Retrospective and cross-sectional analyses of self-reported survey data. SETTING: Six sites of the Longitudinal Assessment of Bariatric Surgery-2 study. PATIENT(S): The study included 1,538 females having bariatric surgery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reported polycystic ovary syndrome (PCOS), pregnancy and fertility history, contraceptive use, and plans for pregnancies. RESULT(S): Mean age was 44.8 years (range, 18-78 years); mean body mass index was 47.2 kg/m2 (range, 33.8-87.3 kg/m2). PCOS had been diagnosed by a health care provider in 13.1% of subjects. Of women who had tried to conceive, 41.9% experienced infertility and 61.4% had a live birth after experiencing infertility. In the whole group, prior live birth was reported by 72.5%. Women who were obese by 18 years old were more likely to report PCOS and infertility and less likely to have ever been pregnant, compared with women who became obese later in life. Future pregnancy was important to 30.3% of women younger than 45 years, whereas 48.6% did not plan to become pregnant in the future. In the year before surgery, 51.8% used contraception. CONCLUSION(S): Self-reporting of obesity by age 18 appears to be related to reproductive morbidity. Women undergoing bariatric surgery have important reproductive health care needs, including reliable contraception and counseling about plans for postoperative pregnancy.

Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism.

CONTEXT: There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement. OBJECTIVE: The aim was to compare assay results from a direct RIA with two LC/MS. DESIGN AND SETTING: We conducted a blinded laboratory study including masked duplicate samples at three laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS). PARTICIPANTS AND INTERVENTIONS: Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared. MAIN OUTCOME MEASURE: We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores. RESULTS: Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (≤50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17). CONCLUSIONS: A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels.

Teaching error disclosure to residents: a curricular innovation and pilot study.

OBJECTIVE: To compare change in obstetrics and gynecology residents' self-efficacy in disclosing medical errors after a formal educational session. METHODS: This was a retrospective postintervention survey to assess change in perceived preparedness to disclose medical errors. We used a 4-hour educational seminar that included a didactic component (30 minutes) and experiential learning with a trained facilitator (3 hours). Change in self-efficacy was measured using a 5-point Likert-type scale (1 is lowest, and 5 is highest) and was compared using sign test (α  =  .05). RESULTS: In our pilot study, 13 of 15 residents reported having previously participated in error disclosure. After the session, residents considered themselves more prepared for the following: to know what to include in and how to introduce error discussions, to deal with a patient's emotional reaction, to respond to a patient's questions regarding how an error occurred, and to recognize one's own emotions when discussing medical errors. Residents believed that they would be likely to use the skills learned in the remainder of residency and in their future career. CONCLUSIONS: This curriculum was associated with improvement in self-efficacy regarding error disclosure. Given the unique malpractice issues that obstetricians/gynecologists face, it seems particularly useful for residents to learn these skills early in their career. In addition, this topic represents an ideal educational opportunity for residencies to improve patient care and to address other core competencies in resident education such as communication skills and professionalism.

Predictors of pregnancy in women with polycystic ovary syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric. OBJECTIVE: The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods. DESIGN, SETTING, AND PARTICIPANTS: We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients' baseline characteristics. INTERVENTIONS: Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception. MAIN OUTCOME MEASURE: The primary outcome of the trial was the rate of live births. RESULTS: Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value. CONCLUSIONS: A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.

Obesity and the role of gut and adipose hormones in female reproduction.

Reproductive function declines at both extremes of human energy balance. The relationship between obesity and reproductive function is complex and incompletely understood. The literature has established the negative impact of excess energy stores on ovulatory function and investigated the mechanisms whereby this occurs. Furthermore, weight loss in obese anovulatory women increases ovulation and conception. Obesity and anti-obesity therapy effects on the endometrium, implantation and early fetal development have received less attention. The discovery of adipokines and enterokines greatly expands the ability to investigate the relationship between obesity, therapies to produce weight loss and reproductive function. In this review, we discuss select adipose and enteric signals. We focus on in vitro, animal and human data that lend biological plausibility to adipokines and enterokines as mediators of obesity and reproduction. Very little published work exists that directly addresses adipocyte and enteric signals in this specific role; therefore, much of this review is on the basis of a synthesis of the literature in three areas: (i) in vitro and in vivo evidence regarding the reproductive effects of these signals; (ii) adipokine and enterokine changes that occur with weight-loss therapies, focusing on hypocaloric diets, bariatric surgery and drugs that target adipocyte or enteric signals and (iii) reproductive changes produced by these weight-loss therapies.