A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.

Obesity is an infertility factor in otherwise normal men. Obese men demonstrate a relative hypogonadotropic hypogonadism. Reduced inhibin B levels and diminished paternity suggest compromised reproductive capacity in this population.

Objective To describe fertility patients' preferences for disposition of cryopreserved embryos and determine factors important to these preferences Design Cross-sectional survey conducted between June 2006 and July 2007 Setting Nine geographically diverse U.S. fertility clinics Participants 1020 fertility patients with cryopreserved embryos Interventions Self-administered questionnaire Main Outcome Measures Likelihood of selecting each of five conventional embryo disposition options: store for reproduction, thaw and discard, donate to another couple, freeze indefinitely, and donate for research; likelihood of selecting each of two alternative options identified in previous research: placement of embryos in the woman's body at an infertile time, and a disposal ceremony; importance of each of 26 considerations to disposition decisions; and views on the embryo's moral status. Results 54% of respondents with cryopreserved embryos were very likely to use them for reproduction, 21% were very likely to donate for research, 7% or fewer were very likely to choose any other option. Respondents who ascribed high importance to concerns about the health or well-being of the embryo, fetus, or future child were more likely to thaw and discard embryos or freeze them indefinitely. Conclusions Fertility patients frequently prefer disposition options not available to them or find available options unacceptable. Restructuring and standardizing the informed consent process and ensuring availability of all disposition options may benefit patients, facilitate disposition decisions and address problems of long term storage.

Objective To determine the effects of high-dose vitamin D on insulin sensitivity in Polycystic Ovary Syndrome (PCOS). Design Randomized placebo-controlled trial. Setting Academic medical center. Patients 28 PCOS women. Interventions Vitamin D3 12,000 International Units or placebo daily for 12 weeks. Main Outcome Measures The primary outcome was quantitative insulin sensitivity check index (QUICKI). Secondary outcomes included glucose and insulin levels during a 75-gram oral glucose tolerance test and blood pressure. Results Twenty-two women completed the study. Compared to placebo, vitamin D significantly increased 25-hydroxyvitamin D (mean (95% confidence interval) in vitamin D group 20.1 (15.7 to 24.5) ng/ml at baseline and 65.7 (52.3 to 79.2) ng/ml at 12 weeks; placebo 22.5 (18.1 to 26.8) ng/ml at baseline and 23.8 (10.4 to 37.2) ng/ml at 12 weeks). There were no significant differences in QUICKI and other measures of insulin sensitivity, however we observed trends towards lower 2-hour insulin and lower 2-hour glucose. We also observed a protective effect of vitamin D on blood pressure. Conclusions In women with PCOS, insulin sensitivity was unchanged with high-dose vitamin D but there was a trend towards decreased 2-hour insulin and a protective effect on blood pressure. Clinical Trial registration number ClinicalTrials.gov Identifier: NCT00907153

Objective To determine if the combination of lifestyle(caloric restriction and exercise) and metformin(MET) would be superior to placebo and lifestyle(PBO) in improving PCOS phenotype. Design Double-blind randomized 6 month trial of MET vs PBO Setting Two academic medical centers Patients 114 subjects Interventions Subjects collected urines daily for ovulation monitoring, had monthly monitoring of hormones/weight, and determination of body composition by DXA, glucose tolerance, and quality of life at baseline and completion. Main outcome measures Ovulation rates and testosterone levels Results Dropout rates were high. There was no significant difference in ovulation rates. Testosterone levels were significantly lower compared to baseline in the MET group at 3 mos but not at 6 mos. There were no differences in weight loss between groups, but MET showed a significant decline at 6 mos compared to baseline(−3.4 kg, 95% CI:(−5.3, −1.5)). We noted divergent effects of MET vs PBO on OGTT indices of insulin sensitivity (increased) and secretion (worsened). Total bone mineral density (BMD) increased significantly in MET. There were no differences in QOL measures between groups. MET had increased diarrhea and headache, but fewer bladder infections and musculoskeletal complaints. Conclusions The addition of metformin to lifestyle produced little reproductive or glycemic benefit in women with PCOS, though our study had limited power due to high dropout. It is not possible at baseline to identify women likely to drop out.

Women with polycystic ovary syndrome (PCOS) are insulin resistant, have insulin secretory defects, and are at high risk for glucose intolerance. We performed this study to determine the prevalence of glucose intolerance and parameters associated with risk for this in PCOS women. Two-hundred and fifty-four PCOS women, aged 14-44 yr, were prospectively evaluated at 2 centers, 1 urban and ethnically diverse (n = 110) and 1 rural and ethnically homogeneous (n = 144). The rural PCOS women were compared to 80 control women of similar weight, ethnicity, and age. A 75-g oral glucose challenge was administered after a 3-day 300-g carbohydrate diet and an overnight fast with 0 and 2 h blood samples for glucose levels. Diabetes was categorized according to WHO criteria. The prevalence of glucose intolerance was 31.1% impaired glucose intolerance (IGT) and 7.5% diabetes. In nonobese PCOS women (body mass index, <27 kg/m2), 10.3% IGT and 1.5% diabetes were found. The prevalence of glucose intolerance was significantly higher in PCOS vs. control women (chi2 = 7.0; P = 0.01; odds ratio = 2.76; 95% confidence interval = 1.23-6.57). Variables most associated with postchallenge glucose levels were fasting glucose levels (P < 0.0001), PCOS status (P = 0.002), waist/hip ratio (P = 0.01), and body mass index (P = 0.021). The American Diabetes Association criteria applied to fasting glucose significantly underdiagnosed diabetes compared to the WHO criteria (3.2% vs. 7.5%; chi2 = 4.7; P = 0.046; odds ratio = 2.48; 95% confidence interval = 1.01-6.69). We conclude that 1) PCOS women are at significantly increased risk for IGT and type 2 diabetes mellitus at all weights and at a young age; 2) these prevalence rates are similar in 2 different populations of PCOS women, suggesting that PCOS may be a more important risk factor than ethnicity or race for glucose intolerance in young women; and 3) the American Diabetes Association diabetes diagnostic criteria failed to detect a significant number of PCOS women with diabetes by postchallenge glucose values.

These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Growth factors have been shown to modulate differentiation of cultured ovarian granulosa cells. Transforming growth factors (TGFs) constitute a family of polypeptide growth factors capable of reversibly inducing anchorage-independent growth in normal cells. Epidermal growth factor (EGF), which has significant structural homology with TGF alpha, has been shown to modulate differentiation of granulosa cells in vitro. Similarly, TGF beta (TGFB) has been found to have significant structural homology with ovarian follicular fluid inhibin. To examine whether TGFB might affect granulosa cell growth or differentiation, rat granulosa cells were cultured in serum-free medium containing insulin for up to 3 days with varying concentrations of TGFB in the presence or absence of FSH. TGFB caused a dose-dependent increase in FSH-stimulated LH/hCG receptor binding, but had no effect on binding in the absence of FSH; TGFB (10.0 ng/ml) further increased FSH-stimulated LH/hCG receptor binding by 48 +/- 8% (P less than 0.02). Similarly, FSH-stimulated progesterone production was increased by TGFB in a dose-dependent manner; TGFB (1.0-10.0 ng/ml) increased FSH-stimulated progesterone production 2- to 3-fold (P less than 0.02). In contrast, EGF (10.0 ng/ml) decreased FSH-stimulated LH/hCG receptor binding by 93 +/- 1% (P less than 0.02). Neither FSH-stimulated intracellular nor extracellular cAMP accumulations were affected by TGFB treatment. However, EGF (10.0 ng/ml) diminished extracellular and intracellular FSH-stimulated cAMP accumulation at 48 and 72 h of culture. Culture protein and DNA content were not significantly affected by TGFB. These results suggest that TGFB may enhance FSH-stimulated LH receptor induction and steroidogenesis by mechanisms that do not further increase net cellular cAMP accumulation; TGFB and EGF can have opposite effects on gonadotropin-dependent differentiation; and products of the TGFB/inhibin gene family may have a capacity for autocrine or paracrine modulation of granulosa cell differentiation.