Search

Context: Obese men with normal semen parameters exhibit reduced fertility but few prospective data are available., Objective: This study aimed to determine the effect of male factors and body mass among the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) participants., Methods: This is a secondary analysis of the PPCOS II trial. A total of 750 infertile women with polycystic ovary syndrome (PCOS) were randomly assigned to up to receive five cycles of letrozole or clomiphene citrate. Females were 18-39-years-old and had a male partner with sperm concentration of at least 14 million/mL who consented to regular intercourse. Analysis was limited to couples with complete male partner information (n = 710)., Results: Male body mass index (BMI) was higher in couples who failed to conceive (29.5 kg/m(2) vs 28.2 kg/m(2); P = .039) as well as those who did not achieve a live birth (29.5 kg/m(2) vs 28.1 kg/m(2); P = .047). At least one partner was obese in 548 couples (77.1%). A total of 261 couples were concordant for obesity (36.8%). After adjustment for female BMI, the association of male BMI with live birth was no longer significant (odds ratio [OR] = 0.85; 95 % confidence interval [CI], 0.68-1.05; P = .13). Couples in which both partners smoked had a lower chance of live birth vs nonsmokers (OR = 0.20; 95 % CI, 0.08-0.52; P = .02), whereas there was not a significant effect of female or male smoking alone. Live birth was more likely in couples with at least three sexual intercourse attempts over the previous 4 weeks (reported at baseline) as opposed to couples with lesser frequency (OR = 4.39; 95 % CI, 1.52-12. 4; P < .01)., Conclusions: In this large cohort of obese women with PCOS, effect of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success.

Over the recent decades, the prevalence of obesity in the United States has increased to epidemic proportions to more than 35% of adults, along with an increased risk of a number of health conditions, including hypertension, adverse lipid concentrations, and type 2 diabetes. The relationships between menopausal transition, weight gain, and obesity are reported but incompletely understood. The association between menopause and these measures has been the subject of many studies, along with examining their effect on reproductive hormones and menopausal symptoms. The purpose of this review is to summarize what is published in the literature on this subject and examine it through: (1) the possible impact of obesity on the timing of menopause; (2) the effect of obesity on menopausal symptoms and reproductive hormones around the time of menopause; and (3) the effect of menopause on obesity, weight gain, and body composition., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Beneficial effects on health of limiting food intake for certain periods of time have been recognized for a long time. While many diets can produce short-term weight loss, most fail to result in a long-lasting impact. Current data suggest that intermittent fasting may be beneficial for overall health and wellbeing. However, the lack of properly designed clinical studies makes it challenging to formulate evidence-based practice recommendations. Potential health risks of drastic changes in food intake are often ignored and might only be revealed after extensive follow-up. This review summarizes the popular intermittent dieting methods and their potential impact on fertility and reproduction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to gonadotrophin-releasing hormone (GnRH) in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous luteinizing hormone (LH) in obese women., Design: Participants underwent a luteal phase frequent blood sampling study. Endogenous LH pulsatility was observed, gonadotrophin-releasing hormone (GnRH) was given in two weight-based doses, and GnRH antagonist was administered followed by recombinant LH., Patients: Regularly menstruating obese (n = 10) and normal weight (n = 10) women., Measurements: Endogenous hypothalamic-pituitary function (as measured by LH pulsatility), pituitary sensitivity (GnRH-induced LH secretion), pharmacodynamics of endogenous LH and pharmacokinetics of exogenous LH were compared between the obese and normal weight groups., Results: There were no statistically significant differences in endogenous LH pulsatility or pituitary responses to two weight-based doses of GnRH between the obese and normal weight women. There were no differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of exogenous LH between the groups. FSH dynamics did not differ between the groups throughout the study., Conclusions: The relative hypogonadotrophic hypogonadism of obesity cannot be explained by differences in LH and FSH luteal phase dynamics or differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics., (© 2014 John Wiley & Sons Ltd.)

Purpose: To determine if etiology of infertility modifies the relationship between the duration of ovarian stimulation and success during assisted reproductive technology (ART) cycles., Methods: A prospectively collected database was analyzed in an academic infertility practice. Eight hundred and twelve infertile women undergoing their initial fresh embryo, non-donor in vitro fertilization (IVF) or Intracytoplasmic Sperm Injection ICSI) cycle between January 1999 and December 2010 were evaluated. Clinical pregnancy was the main outcome measured., Results: Out of 663 cycles resulting in oocyte retrieval, 299 produced a clinical pregnancy (45.1%). Women who achieved a clinical pregnancy had a significantly shorter stimulation length (11.9 vs. 12.1 days, p = 0.047). Polycystic ovary syndrome (PCOS) was the only etiology of infertility that was significantly associated with a higher chance for clinical pregnancy and was a significant confounder for the association of duration and success of treatment. Women with 13 days or longer of stimulation had a 34 % lower chance of clinical pregnancy as compared to those who had a shorter cycle (OR 0.66, 95% CI:0.46-0.95) after adjustment for age, ovarian reserve, number of oocytes retrieved, embryos transferred and PCOS diagnosis., Conclusion: Prolonged duration of stimulation is associated with decreased ART success for all couples, except for women with PCOS.

Context: Although there is evidence of metabolic risks in young women with irregular menses and androgen excess, persistence of risks after menopause is unclear., Objective: The objective of the study was to determine the impact of menopause on the cardiometabolic profile in women with high androgens and a history of menstrual irregularity., Methods: Study of Women's Health Across the Nation is a longitudinal cohort study. Data from 1929 women without metabolic syndrome (MetS) at baseline were analyzed for incidence of MetS, self-reported stroke, and myocardial infarction. Cox hazard ratios (HRs) were estimated, adjusting for age, ethnicity, body mass, smoking, menopausal status, and study site., Results: Among MetS-free women at baseline, 497 new cases were identified during 20 249 woman-years of follow-up over 12 years. Women with hyperandrogenemia (HA) and oligomenorrhea (Oligo) developed incident cases of MetS at a comparable rate compared with their counterparts: eumenorrheic, normoandrogenic women [HR 1.4 (0.9-2.2)], oligomenorrheic, normoandrogenic women [HR 1.3 (0.8-2.2)], and eumenorrheic hyperandrogenic women [HR 1.2 (0.7-1.8)]. Smoking and obesity were the strongest predictors of incident MetS. There was no significant difference in incidence of self-reported stroke or MI by HA/Oligo status., Conclusions: Longitudinal evidence suggests that a history of androgen excess and menstrual irregularity is not associated with worsening of metabolic health after menopause. Our findings challenge the notion that a history of concurrent HA and Oligo reflects ongoing cardiometabolic risk in postmenopausal women.

Objective: It was hypothesized that aromatase inhibitor (AI)-induced interruption of estradiol negative feedback would modulate the reproductive hormone profile of obese women., Methods: Regularly cycling women aged 18-40 years with a BMI of 18-25 kg/m(2) (normal weight, n = 10) or >30 kg/m(2) (obese; n = 12) were given AI daily for 7 days. Urinary hormone profiles were compared between groups. Fourteen eumenorrheic, normal weight women not receiving AI stimulation served as historical controls. Urinary metabolites for LH, FSH, estradiol (E1c), and progesterone (Pdg) were measured and normalized to a 28-day cycle. Serum estrone and estradiol were measured in the late follicular phase., Results: Whole-cycle LH, FSH, and luteal Pdg excretion did not differ between obese (BMI = 37.1 + 7 kg/m(2) ) and normal weight women treated with AIs, although LH was greater in stimulated compared with unstimulated normal weight women. Whole cycle mean E1c was lower in AI-stimulated obese and normal weight participants compared with nonstimulated normal weight controls, but obese women treated with AI excreted far less E1c (467.7 ± 217.4 μg/mg Cr) than AI-treated normal weight women (911.4 ± 361.8 μg/mg Cr; P = 0.02). Follicular phase serum estrone and estradiol were also lower in AI-treated obese women versus AI-treated normal weight women (61.7 ± 22.8 and 18.3 ± 3.7 pg/ml versus 99.1 ± 30.5 and 37.7 ± 5.9 pg/ml, respectively; P = 0.034 and 0.005)., Conclusions: Normal gonadotropin output and luteal function occur at the expense of reduced E1c excretion in AI-treated women, and this discrepancy is particularly evident in obese women., (Copyright © 2014 The Obesity Society.)

Context: Assisted reproductive technology (ART) cycle cancelation rates are increased among overweight and obese women; however, the reasons for this are not completely clear. Premature luteinization due to inadequate endogenous gonadotropin suppression is a possibility for this higher risk of cancellation., Objective: The objective of the study was to investigate the impact of female obesity on the pharmacokinetics of cetrorelix (GnRH antagonist)., Design: This was an interventional study., Setting: The study was conducted at a university clinical and translational research center., Participants: Regularly menstruating obese (n = 10) and normal-weight (n = 10) women participated in the study., Interventions: A frequent blood sampling study was performed after a GnRH antagonist was administered, followed by recombinant LH., Main Outcomes Measured: Pharmacokinetics of cetrorelix in obese vs normal weight women were measured., Results: Five of the obese women (50%) and none of the normal-weight women had a rebound of LH (defined as >50% increase in LH level from nadir) over the 14-hour postdose observation period. The obese group had a significantly decreased distributional half-life of cetrorelix compared with the normal-weight group (8.1 ± 1.6 vs 12.7 ± 6.2 hours, P = .02). The obese group exhibited increased clearance of cetrorelix compared with the normal-weight group (25.8 ± 6.8 vs 20.1 ± 8.3 L/h, P = .058)., Conclusions: The altered pharmacokinetics of cetrorelix in obese women may lead to premature ovulation during ART, and this could be one of the mechanisms that results in increased cycle cancelation in this group of women. In accordance with the higher gonadotropin requirements for obese women undergoing ART, weight-based dosing of GnRH antagonists may be required.

Purpose: The association between pronuclear (PN) scoring of embryos from assisted reproductive technology (ART) and clinical pregnancy remains controversial. We hypothesized that embryos with PNs scored on the day of fertilization check offer better embryo selection on day 3 and higher CPR compared to non-PN scored embryos., Methods: Patients (19-46 years) undergoing IVF/ICSI cycles at Montefiore's Institute for Reproductive Medicine and Health between January 2006 and December 2009 were included in our study. We analyzed fresh day 3 cycles only with autologous oocytes and partner's fresh sperm (n = 344). A total of 1,899 embryos were included. We compared CPR from non-PN scored embryos (Group 1, n = 835) with PN scored embryos (Group 2, n = 1,064). Composite scores by patient were developed based on embryo disposition. We also assessed traditional embryo grading derived from cell number, fragmentation and cell symmetry. Data analysis included chi square and t test to determine if PN scoring was associated with improved CPR, and to compare the additional variables., Results: CPR between Group 1 and Group 2 were not different (p = 0.91). CPR was significantly associated with female age, number of mature oocytes retrieved, number of day 3 embryos and grade of embryos transferred on day 3 (p < 0.05)., Conclusion: PN scoring was not associated with improved CPR in day 3 embryo transfers. Mean grade of transferred embryos continues to be a well-established, independent predictor of CPR. We conclude that further refinement of embryo grading by PN scoring is not beneficial.

Specific alterations in the pulsatility of luteinizing hormone (LH) are linked to obesity-related subfertility in ovulatory women. Vervet monkeys (Chlorocebus aethiops sabaeus) are an Old World nonhuman primate that develops obesity and has a menstrual cycle similar to humans. We evaluated follicular-phase LH pulses in 12 adult normal-weight female vervets. Serum was collected every 10 min for 4 h by using a tether device in conscious, freely moving monkeys on menstrual cycle days 2 through 5. Serum estradiol was collected daily during the follicular phase to identify the luteal-follicular transition. For comparison, we used data from 12 ovulatory normal-weight women who had undergone frequent blood sampling of early-follicular LH. LH pulse frequency was similar, with 2.8 ± 0.7 LH pulses during 4 h in vervets compared with 2.3 ± 0.7 LH pulses during 4 h in women. The LH pulse mass (percentage change in the pulse peak over the preceding nadir) was 123.2% ± 27.4% in vervets and 60.9% ± 14.9% in humans. The first day of low serum estradiol after the follicular-phase peak was denoted as the day of the luteal-follicular transition. Luteectomy was performed on luteal days 7 through 9, and corpora lutea were confirmed by histology. We demonstrate that follicular LH patterns in vervets are similar to those in humans and that the luteal phase is easily identified by monitoring daily serum estradiol. These findings demonstrate that vervet monkeys are a suitable animal model for evaluating LH pulse dynamics longitudinally in studies of diet-induced obesity.

This prospective, cross-sectional study of 60 women compares self-reported height, weight, and BMI with measured values. Self-reported BMI (29.0±8.37 kg/m(2)) was slightly lower than measured BMI (29.1±8.38 kg/m(2)) (p=0.4). Eighty percent of participants reported a BMI in the same category in which their BMI was measured. Pearson's correlation coefficient for height (0.96, p<0.001), weight (0.99, p<0.001), and BMI (0.99, p<0.001) were high. Reproductive age women accurately reported their height and weight., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Adenomyosis is a benign infiltration of endometrial stroma and glands into the myometrium. Until the advent and advancement of imaging techniques such as transvaginal ultrasound scan (TVUS) and magnetic resonance imaging (MRI), the diagnosis of adenomyosis could only be made with confidence using histology following hysterectomy., Case: The patient is a 37-year-old woman, with a long history of secondary infertility. A hysterosalpingogram (HSG) and a pelvic MRI showed two separate uterine cavities. The patient underwent laparoscopy and hysteroscopy revealing a bicornuate appearance of the uterus and a uterine septum. Resection of the septum showed adenomyosis on histologic examination., Comment: Adenomyosis of uterine septum should be considered if MRI shows features of adenomyosis elsewhere in the uterus with thickened junctional zone. Further research is needed to investigate this association with the pathogenesis of adenomyosis.

Objective: Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested., Design and Methods: Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR., Results: Couples with male body mass index (BMI) over 25 kg m(-2) (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m(-2) was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected., Conclusions: Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner., (Copyright © 2013 The Obesity Society.)

Obesity is a pandemic and is associated with multiple medical problems including subfertility. Male obesity has been associated with altered semen parameters and reproductive hormonal levels, including a reduced testosterone:estradiol (T:E₂) ratio. Treatment methods employed for obesity-related male subfertility include gonadotropin administration, weight loss, and aromatase inhibitors. Letrozole is a highly effective nonsteroidal aromatase inhibitor that has been used to treat male subfertility in several case series with promising results. Adequately designed randomized controlled studies are needed to produce evidence-based data on the role of aromatase inhibitors in male subfertility management and evaluate the side-effect profile., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.

The objective of the current study was to characterize luteal function in vervet monkeys. Urine from 12 adult female vervets housed at an academic research center was collected for 10 weeks from single-caged monkeys in order to assess evidence of luteal activity (ELA) as determined by urinary excretion of pregnanediol glucuronide (Pdg) and estrone conjugates (E1c). Dual energy X-ray absorptiometry (DXA) was performed on the monkeys to assess body composition, bone density, and fat mass. Menstrual cyclicity was determined using records of vaginal bleeding. ELA was observed in 9 monkeys and was characterized by a late follicular rise in E1c followed by a progressive increase in Pdg excretion. Mean menstrual cycle length was 26.7 ± 3.8 days and the average day of luteal transition was 14 ± 1.8. Three monkeys without ELA had a clearly defined E1c rise (mean 12-fold from nadir) followed by an E1c drop that was not accompanied by Pdg rise and coincided with vaginal bleeding. Among the 9 ELA monkeys, excretion of E1c tended to negatively associate with fat mass, although this finding did not reach statistical significance (r = -0.61, p = 0.08). Similar to women, vervet monkeys experience an increase in E1c late in the follicular phase of the menstrual cycle which is followed by a subsequent luteal Pdg peak. Assessment of urinary reproductive hormones allows for identification of cardinal menstrual cycle events; thus, the similarity of vervet cycles to human menstrual cycles makes them a useful model for obesity-related human reproductive impairment.

Normal function of mitochondria plays an essential role in enabling reproductive capacity. To date, few studies have investigated the role of promoting mitochondrial health in relation to fertility in humans. Selected nutritional interventions have demonstrated a potential to enhance mitochondrial function, suggesting a promise for future research for fertility treatment. This review summarizes the extant literature and highlights a putative role of particular nutrients in promotion of mitochondrial function, including in vitro, animal and human studies. Strong basis exists to advocate for further investigation of nutritional treatments for infertility patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine the prevalence of nucleolar channel systems (NCSs) by uterine region, applying continuous quantification., Design: Prospective clinical study., Setting: Tertiary care academic medical center., Patient(s): Forty-two naturally cycling women who underwent hysterectomy for benign indications., Intervention(s): NCS presence was quantified by a novel method in six uterine regions-fundus, left cornu, right cornu, anterior body, posterior body, and lower uterine segment (LUS)-with the use of indirect immunofluorescence., Main Outcome Measure(s): Percentage of endometrial epithelial cells (EECs) with NCSs per uterine region., Result(s): NCS quantification was observer independent (intraclass correlation coefficient 0.96) and its intrasample variability low (coefficient of variation 0.06). Eleven of 42 hysterectomy specimens were midluteal, ten of which were analyzable with nine containing >5% EECs with NCSs in at least one region. The percentage of EECs with NCSs varied significantly between the LUS (6.1%; interquartile range [IQR] 3.0-9.9) and the upper five regions (16.9%; IQR 12.7-23.4), with fewer NCSs in the basal layer of the endometrium (17 ± 6%) versus the middle (46 ± 9%) and luminal layers (38 ± 9%) of all six regions., Conclusion(s): NCS quantification during the midluteal phase demonstrates uniform presence throughout the endometrial cavity, excluding the LUS, with a preference for the functional luminal layers. Our quantitative NCS evaluation provides a benchmark for future studies and further supports NCS presence as a potential marker for the window of implantation., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The ketogenic diet was first developed in the 1920s as a treatment for epilepsy in an attempt to create a prolonged physiologic starvation state. Since that time, the diet has been found to have other therapeutic effects, most of which are neurologic. Other diets, mostly based on the principals of caloric restriction, have been shown to improve fertility in certain populations. We explore the data, both clinical and laboratory, for potential fertility enhancing benefits of the ketogenic diet, beyond just caloric restriction or weight loss., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose of Review: Metabolic syndrome (MetS) is a cluster of characteristics that increase the risk of cardiovascular disease and type 2 diabetes mellitus. We will review the most interesting and relevant studies on metabolic correlates of menopause published over the last year., Recent Findings: In the past year, studies have shifted focus from effects on cardiovascular disease and diabetes to effects of MetS on breast cancer as well as menopausal symptoms. Studies have found and further confirmed its negative effect on both breast cancer and menopausal symptoms. Focus has also been on treatment options including both lifestyle and pharmacologic. Recent studies also further investigate markers/predictors as well as genetic components influencing MetS development., Summary: Over a quarter of the US population is affected by metabolic disease at midlife, and some studies have shown that the incidence of MetS increases with menopause. There are now more Americans who are age 65 and older than at any other time in US history. Thus, it is becoming ever more important to understand metabolic health, as well as the consequences of MetS.

The Society for Gynecologic Investigation (SGI) hosted its 59th Annual Meeting in San Diego (CA, USA) on 21-24 March 2012. The program attracted 1313 attendees, 918 from the USA and Canada and 395 from the rest of the world. The event was hosted by the SGI president Stephen J Lye and the program director Stephen Matthews. The mission of the SGI is to discover, review, report and transfer new knowledge through creative research and training, community integration and partnerships that improve the reproductive health of women everywhere. More than 1100 abstracts were presented at the meeting, 172 of which were oral presentations. A selection of notable presentations are highlighted here.

Context: Young reproductive-age women with irregular menses and androgen excess are at high risk for unfavorable metabolic profile; however, recent data suggest that menstrual regularity and hyperandrogenism improve with aging in affected women approaching menopause., Objective: The objective of the study was to determine whether women with hyperandrogenemia (HA) and a history of oligomenorrhea (Oligo) are at an elevated risk for metabolic syndrome (MetS) at the early stages of menopausal transition., Methods: Baseline data from 2543 participants (mean age of 45.8 yr) in the Study of Women's Health Across the Nation were analyzed. Women with a lifetime history of more than one 3-month interval of nongestational and nonlactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum testosterone was used to define HA. Women with normal serum androgens and eumenorrhea were used as the reference group. Logistic regression models generated adjusted odds ratios (AOR), controlling for age, ethnicity, body mass index, smoking, and study site., Results: Oligo was associated with MetS only when coincident with HA [AOR of 1.93 for Oligo and HA [95% confidence interval (CI) 1.17-3.17], AOR of 1.25 for Oligo and normal androgens (95% CI 0.81-1.93)]. In contrast, HA conferred a consistently significant risk for MetS, regardless of the menstrual frequency status [AOR of 1.48 for HA and eumenorrhea (95% CI 1.15-1.90)]., Conclusions: Our results suggest that HA but not history of Oligo is independently associated with the risk of prevalent MetS in pre- and perimenopausal women in their 40s.

Caloric restriction, decreasing caloric intake by 20-30%, was first shown to extend life in rats nearly 80 years ago. Since that time, limiting food intake for longevity has been investigated in species from yeast to humans. In yeast and lower animals, caloric restriction has repeatedly been demonstrated to lengthen the life span. Studies of caloric restriction in non-human primates and in humans are ongoing and initial results suggest prolongation of life as well as prevention of age-related disease. There is also data in rodents suggesting that short term caloric restriction has beneficial effects on fertility. Although caloric restriction has many positive effects on health and longevity, quality of life on a restricted diet as well as the ability to maintain that diet long term are concerns that must be considered in humans., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Context: Thyroid cancer survivors represent a unique population in which the potential long-term effects of brief periods of intentional thyroid hormone withdrawal and/or prolonged periods of iatrogenic hyperthyroidism on body weight and body mass were evaluated., Objectives: The objectives of this study were to characterize body mass changes over several years in a cohort of thyroid cancer patients with iatrogenic hyperthyroidism and to compare these changes with the expected weight gain in age-matched healthy control populations. We also evaluated the possibility that the method of preparation [thyroid hormone withdrawal (THW) vs recombinant human TSH (rhTSH)] for radioactive iodine remnant ablation may be associated with differences in body mass at the time of the final follow-up. DESIGN/SETTING/PATIENTS/INTERVENTIONS: A retrospective review identified 153 patients with thyroid cancer who underwent total thyroidectomy at one major medical centre. Of the 153 patients, 143 also had radioactive iodine remnant ablation: 70 after THW and 73 after rhTSH., Main Outcome Measures: Change in weight and BMI at 1-2 and 3-5 years of follow-up points were examined. Annualized weight variation within the cohort was compared with age-matched population controls expressed in kilogram/year., Results: Significant weight gain was noted for the full cohort after 3-5 years of follow-up as compared to baseline (76 ± 21 kg at baseline vs 79 ± 23 kg at 3-5 years of follow-up, P < 0·01), which represented a 3·2% increase. Female and male patients with thyroid cancer experienced 0·46 and 0·94 kg/year gain in weight, respectively, which is similar or somewhat higher than previously published age-matched population controls (ranging from 0·23 to 0·34 kg/year). When expressed as per cent change and comparing the final weight to the pre-operative baseline, the rhTSH group experienced approximately a 1·7% increase in weight compared with the 3·9% increase seen with THW patients (P = 0·02). When expressed as kg/year change, the rhTSH cohort had 0·34 kg/year change compared with the 0·64 kg/year change seen in the thyroid hormone withdrawal patients (P = 0·02)., Conclusion: In otherwise, healthy patients with differentiated thyroid cancer, significant weight gain occurred during the 3-5 years of follow-up despite ongoing thyrotropin suppression. The data suggest that mild iatrogenic hyperthyroidism does not promote weight loss or prevent ageing-related weight gain. Greater weight gain was seen in patients prepared for radioactive remnant ablation with THW than with rhTSH., (© 2012 Blackwell Publishing Ltd.)

Objective: To review reasons for suboptimal recruitment for a randomized controlled trial (RCT) of varicocelectomy versus intrauterine insemination (IUI) for treatment of male infertility and to suggest means for improving future study recruitment., Design: Survey of Reproductive Medicine Network (RMN) participating sites., Setting: Reproductive Medicine Network., Patient(s): None., Intervention(s): None., Main Outcome Measure(s): Ascertain reasons for inadequate recruitment and suggest improvements for future varicocelectomy trails., Result(s): This study screened seven and enrolled three couples, with the first couple randomized on June 30, 2010. The study was subsequently stopped on March 30, 2011. The following themes were cited most frequently by sites and therefore determined to be most likely to have played a role in suboptimal recruitment: [1] men must be screened at the beginning of a couple's infertility evaluation, [2] inclusion of infertile women who had failed previous fertility interventions appeared to be associated with the couple's intolerance of a placebo arm, and [3] an apparent bias against the use of unstimulated IUI cycles indicated a prejudicial preference for surgical intervention in the male partner., Conclusion(s): Improved recruitment may be realized through screening infertile men as early as possible while minimizing study-related time commitments. Focused patient education may promote improved equipoise and acceptance of a placebo arm in male infertility studies. Creative approaches to implementing varicocelectomy trials must be considered in addition to having a network of motivated researchers who carry a high volume of possible study participants because very large numbers may need to be screened to complete the clinical trial enrollment., (Published by Elsevier Inc.)

Objective: To evaluate whether ethnicity is associated with involuntary childlessness and perceived reasons for difficulties in becoming pregnant., Design: Cross-sectional analysis of baseline data from a longitudinal cohort., Setting: Multiethnic, community-based observational study of US women., Patient(s): Women in midlife (3,149), aged 42-52 years., Intervention(s): None., Main Outcome Measure(s): Involuntary childlessness and perceived etiology of infertility., Result(s): One hundred thirty-three subjects (4.2%) were involuntarily childless, defined by a reported history of infertility and nulliparity. Ethnicity was significantly associated with self-reported involuntary childlessness. After controlling for economic and other risk factors, African American (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.15-0.59) and Chinese women (OR 0.36; 95% CI 0.14-0.90) were less likely to suffer from involuntary childlessness compared with non-Hispanic white women. In addition, 302 subjects reported a perceived etiology of infertility. An unexpectedly large proportion of these women (24.5%, 74 of 302) reported etiologies not known to cause infertility (i.e., tipped uterus, ligaments for tubes were stretched), with African American women having been most likely to report these etiologies (OR 2.81; 95% CI 1.26-6.28) as the reason for not becoming pregnant., Conclusion(s): Ethnicity is significantly associated with involuntary childlessness and perceived etiology of infertility. Misattribution of causes of infertility is common and merits further consideration with respect to language or cultural barriers, as well as possible physician misattribution., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between the number of mature (metaphase II [MII]) oocytes per assisted reproductive technology (ART) cycle and the likelihood of live birth., Design: Retrospective study., Setting: Academic infertility practice., Patient(s): Seven hundred thirty-seven infertile women undergoing their initial fresh embryo, nondonor IVF or intracytoplasmic sperm injection cycle at Montefiore's Institute for Reproductive Medicine and Health between January 2002 and December 2008., Intervention(s): None., Main Outcome Measure(s): Live birth., Result(s): Two hundred twenty-four cycles resulted in a live birth (30.4%). Live birth cycles had significantly more MII oocytes obtained per cycle as compared with their unsuccessful counterparts (11.0 ± 5.9 vs. 9.7 ± 6.2, respectively). Multivariate logistic regression was done to determine the minimum number of MII oocytes per cycle as a predictor of live birth after adjustment for age and historical maximum FSH values. Cycles that included the average number of MII in this cohort were used as a reference group. For cycles with five or fewer MII oocytes obtained, there was a statistically significant decrease in the likelihood of a live birth as compared with the reference group (odds ratio 0.61, 95% confidence interval 0.38-0.99). However, cycles with six or fewer obtained MII oocytes were not less likely to result in a live birth when compared with the reference group (odds ratio 0.69, 95% confidence interval 0.45-1.08)., Conclusion(s): In our cohort, there was an advantage to obtaining six or more MII oocytes during the fresh oocyte retrieval compared with five or fewer oocytes. There was not an advantage, however, to obtaining 10 or more or 15 or more oocytes as compared with obtaining 6-9 oocytes. The strategy of aiming for a greater number of oocytes in an ART cycle should be revisited., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To better understand the site and mode of action of aromatase inhibitors., Design: Prospective study., Setting: Academic research environment., Patient(s): Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls., Intervention(s): 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes., Main Outcome Measure(s): Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests., Result(s): Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls., Conclusion(s): These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Male infertility affects approximately 6% of reproductive-aged men. It has been suggested that overweight men or men with obese body mass index (BMI) experience prolonged time to pregnancy, though the influence of male BMI on fertility remains understudied., Aims: We hypothesized that BMI is inversely correlated with fertility, manifested by reduced sperm concentration, motility, and morphology., Methods: Males of age 18 to 50 with semen analyses and self-reported BMI were included (n = 530). Patient parameters analyzed included age, BMI, smoking, urological, and fertility history. Leutinizing hormone (LH), Follicle-stimulating hormone, testosterone, steroid hormone-binding globulin (SHBG) and free androgen index (FAI) levels (n = 55), and selective serotonin reuptake inhibitor (SSRI) use (n = 12) were also measured., Results: The men in this study had a mean BMI of 28.2 ± 4.9 kg/m(2) (range = 15-60), which is considered overweight, and a mean semen concentration of 55.4 ± 46.8 million/mL, which is in normal range, according to WHO standard. No consistent relationship was observed between increasing BMI and sperm concentration, motility, or morphology, although the testosterone levels trended downward with increasing BMI; there was a suggestion for decreased sperm concentration in current smokers. Men treated with combination SSRI and other psychotropic agent therapy (n = 12) had significantly reduced sperm motility (P = .009). Not unexpectedly, prior urological surgery (n = 77) was associated with lower sperm concentration (P = .0001) and morphology (P = .0008). When in vitro fertilization-embryo transfer (IVF-ET) was used as a treatment modality (n = 121), male BMI was not a significant predictor of clinical pregnancy (P = .06)., Conclusions: In our study, we did not observe a significant association between male BMI and sperm concentration, motility or morphology, or clinical pregnancy following IVF-ET. Significantly, SSRI use may affect sperm parameters negatively.

Objective: To determine whether nucleolar channel systems (NCSs) in the midluteal endometrium are associated with overall fertility status and/or with unexplained infertility., Design: Retrospective and prospective clinical studies., Setting: Repository of stored specimens from prior multicenter study and private infertility center., Patient(s): Retrospective study that included 97 women (49 fertile couples, 48 infertile couples) who had been randomized for endometrial biopsy during the midluteal or late luteal phase. The prospective study included 78 women with a variety of infertility diagnoses., Intervention(s): Endometrial biopsies were obtained and assessed for the presence of NCSs by indirect immunofluorescence., Main Outcome Measure(s): The presence of NCS was graded semiquantitatively and dichotomized as normal versus low or absent., Result(s): Normal presence of NCS was significantly associated with the midluteal phase compared with the late luteal phase (80% vs. 29%). However, there was no association between presence of NCS and fertility status or between presence of NCS and unexplained infertility., Conclusion(s): Midluteal phase endometrium consistently forms NCSs regardless of fertility status, including unexplained infertility. This indicates a possible role for the NCS in initiating the window of endometrial receptivity. However, the consistent presence of NCSs across several different types of infertility challenges the likelihood that inadequate secretory transformation is a cause of infertility., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Method: To test the hypothesis that psychosocial symptomatology differs by country of origin and acculturation among Hispanic women, we examined 419 women, aged 42-52 years at baseline, enrolled in the New Jersey site of the Study of Women's Health Across the Nation (SWAN). Women were categorized into six groups: Central (CA, n = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (NHC, n = 142). Acculturation, depressive symptoms, hostility/cynicism, mistreatment/discrimination, sleep quality, social support, and perceived stress were assessed at baseline. Physical functioning, trait anxiety and anger were assessed at the fourth annual follow-up. Comparisons between Hispanic and non-Hispanic Caucasians used χ², t test or non-parametric alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five Hispanic sub-groups. Multivariable regression models used PR women as the reference group., Results: Hispanic women were overall less educated, less acculturated (p < 0.001 for both) and reported more depressive symptoms, cynicism, perceived stress, and less mistreatment/discrimination than NHCs. Along with D women, PR women reported worse sleep than Cu women (p < 0.01) and more trait anxiety than SA and Cu women (p < 0.01). Yet, PR women were most acculturated (21.4% highly acculturated vs. CA (0.0%), D (4.8%), SA (4.8%) and Cu (2.3%) women; p < 0.001). In regression models, PR women reported depressive symptoms more frequently than D, Cu, or SA women, and reported trait anxiety more frequently than Cu or SA women. Greater acculturation was associated with more favorable psychosocial status, but PR ethnicity was negatively related to psychosocial status., Conclusion: Psychosocial symptomatology among Hispanic women differs by country of origin and the relatively adverse profile of Puerto Rican women is not explained by acculturation.

Purpose: to evaluate whether the duration of gonadotropin stimulation predicts the likelihood of live birth after ART., Methods: all IVF or ICSI cycles using fresh autologous oocytes at our institution between January 2004 and December 2007 were analyzed., Results: out of 699 cycles resulting in oocyte retrieval, 193 produced a live birth (27.6%). Women who achieved a live birth had a significantly shorter stimulation phase (11.1 vs. 11.5 days, respectively). Multivariable analysis suggested that 13 days or longer of stimulation decreased the likelihood of a live birth by 53% as compared to cycles that were 10-12 days long (odds ratio [OR] 0.47; 95% confidence interval [CI]: 0.30-0.75) after adjustment for female age, maximum historical FSH, total dose of gonadotropin received, oocytes retrieved, embryos transferred, antagonist suppression and PCOS diagnosis., Conclusions: prolonged duration of gonadotropin stimulation is an independent negative predictor of ART success in our cohort.

The incidence of metabolic syndrome increases substantially during perimenopause and early menopause. Postmenopausal women are at a higher risk of hypertension, proatherogenic lipid changes, diabetes, and severe cardiovascular disease as compared with their premenopausal counterparts. Whether or not menopause has a causative contribution to the deteriorating metabolic profile that is independent of chronological aging has been a subject of many studies. Menopausal transition is associated with significant weight gain (2 to 2.5 kg over 3 years on average), which is not dissimilar to that in premenopausal women of like age. Concomitantly, there is an increase in abdominal adiposity and a decrease in energy expenditure, phenomena that have been postulated to explain the higher risk of metabolic syndrome and increases in cholesterol and triglycerides. Hypertension and diabetes become more prevalent with age and should be timely diagnosed and treated. Lifestyle changes including moderately decreased caloric intake and aerobic exercise could prevent proatherogenic changes and weight gain observed with aging. Accurate prediction of cardiovascular risk in midlife women is essential to help identify the subset of women who are likely to benefit from intensive management of metabolic risk factors. This review focuses on metabolic changes associated with menopausal transition, specifically alterations in weight, waist circumference, body fat distribution, energy expenditure, and circulating biomarkers including adipokines., (© Thieme Medical Publishers.)

Purpose: To evaluate if elevated male body mass influences success after assisted reproductive technologies, Methods: Retrospective study of 290 cycles., Results: Male body mass index greater than 25.0 kg/m² was associated with significantly lower clinical pregnancy (53.2% vs. 33.6%). Multivariable logistic regression indicated that the likelihood of clinical pregnancy was decreased if the male partner was overweight after in vitro fertilization but not after intracytoplasmic sperm injection (odds ratios: 0.21 [0.07-0.69] vs. 0.75 [0.38-1.49], respectively) after adjustment for number of embryos transferred, sperm concentration, female age and body mass., Conclusion: In this cohort, overweight status of the male partner was independently associated with decreased likelihood of clinical pregnancy after in vitro fertilization but not after intracytoplasmic sperm injection. A detrimental impact of higher male body mass was observed after adjusting for sperm concentration, suggesting that intracytoplasmic sperm injection may overcome some obesity related impairment of sperm-egg interaction.

Objectives: Hispanics have less favorable cardiovascular risk profiles relative to other groups, although little is known regarding variability in risk profiles according to country of origin. Our goal was to examine the association of cardiovascular risk factors with country of origin and acculturation in a cohort of middle-aged Hispanic women., Setting: Baseline data for participants at the New Jersey Site of the Study of Women's Health Across the Nation (SWAN)., Participants: 419 women, aged 42-52 years, comprising 142 non-Hispanic Whites and 277 Hispanic: Central American (n = 29), South American (n = 106), Puerto Rican (n = 56), Dominican (n = 42) and Cuban (n = 44)., Main Outcome Measures: BMI, smoking, blood pressure, lipid profiles, and presence of hypertension, hyperlipidemia, diabetes and metabolic syndrome were compared using univariate and multivariable models., Results: LDL and HDL varied significantly across Hispanic subgroups (overall P < or = .05). Prevalence of metabolic syndrome was greatest in Puerto Rican women (48.2% vs 40.0%, 35.0%, 13.9% and 29.3% in Central American, South American, Dominican and Cuban women, respectively, P = .016). Central American women were least likely to smoke (P < .05 vs Puerto Rican, Cuban and South American). Prevalence of hypertension and diabetes were similar across groups. Differences in lipids and metabolic syndrome were not explained by acculturation, financial strain, education, physical activity, smoking or dietary fat intake., Conclusions: There is significant heterogeneity in cardiovascular risk status among middle-aged Puerto Rican, Cuban, Dominican, Central American and South American women, not explained by acculturation or socioeconomic indicators. These differences may be important for targeting screening and preventive interventions.

Introduction: Since the designation of people as Hispanic involves the amalgamation of a number of different cultures and languages, we sought to test the hypothesis that menopausal symptoms would differ among Hispanic women, based upon country of origin and degree of acculturation., Methods: A total of 419 women, aged 42-52 years at baseline, were categorized as: Central American (CA, n = 29) or South American (SA, n = 106), Puerto Rican (PR, n = 56), Dominican (D, n = 42), Cuban (Cu, n = 44) and non-Hispanic Caucasian (n = 142). We assessed vasomotor symptoms, vaginal dryness and trouble in sleeping. Hispanics and non-Hispanic Caucasians were compared using the chi(2) test, t test or non-parametric alternatives; ANOVA or Kruskal-Wallis testing examined differences among the five Hispanic sub-groups. Multivariable regression models used PR women as the reference group., Results: Hispanic women were overall less educated, less acculturated (p < 0.001 for both) than non-Hispanic Caucasians and more of them reported vasomotor symptoms (34.1-72.4% vs. 38.3% among non-Hispanic Caucasians; p = 0.0293) and vaginal dryness (17.9-58.6% vs. 21.1% among non-Hispanic Caucasians, p = 0.0287). Among Hispanics, more CA women reported vasomotor symptoms than D, Cu, SA, or PR women (72.4% vs. 45.2%, 34.1%, 50.9%, and 51.8%, respectively). More CA (58.6%) and D women (38.1%) reported vaginal dryness than PR (17.9%), Cu (25.0%) and SA (31.4%) women. More PR and D women reported trouble in sleeping (66.1 and 64.3%, respectively) compared to CA (51.7%), Cu (36.4%), and SA (45.3%) women., Conclusion: Symptoms associated with menopause among Hispanic women differed by country of origin but not acculturation. Central American women appear to be at greatest risk for both vasomotor symptoms and vaginal dryness.

Objective: To evaluate whether adolescent obesity is associated with difficulties in becoming pregnant later in life., Design: Cross-sectional analysis of baseline data from a longitudinal cohort., Setting: Multiethnic, community-based observational study of U.S. women., Patient(s): Three thousand one hundred fifty-four midlife women., Main Outcome Measure(s): Lifetime nulliparity and lifetime nulligravidity., Result(s): Five hundred twenty-seven women (16.7%) women had never delivered a baby. Participants were categorized by self-reported high school body mass index (BMI): underweight (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (>30 kg/m(2)). The prevalence of lifetime nulliparity increased progressively across the high school BMI categories: 12.7%, 16.7%, 19.2%, and 30.9%, respectively. Multivariable logistic regression analysis confirmed that women who were obese adolescents had significantly higher odds of remaining childless compared with normal weight women (odds ratio [OR] 2.84; 95% confidence interval [CI], 1.59-5.10) after adjusting for adult BMI, history of nongestational amenorrhea, marital status, ethnicity, study site, and measures of socioeconomic status. Furthermore, adolescent obesity was associated with lifetime nulligravidity (OR = 3.93; 95% CI, 2.12-7.26)., Conclusion(s): Adolescent obesity is associated with lifetime nulliparity and nulligravidity in midlife U.S. women., (Copyright 2010 American Society for Reproductive Medicine. All rights reserved.)

A burgeoning pandemic of obesity is well characterized. 41% of U.S. adults are projected to be obese by 2015 and obesity, a potentially modifiable risk, is emerging as a leading predictor of lifetime health. The wide spectrum of morbidities related to excess body mass includes risks for diabetes, hypertension, coronary artery disease, dyslipidemia, malignancy, venous thrombosis, degenerative joint disease, pulmonary compromise, sleep apnea, cholelithiasis, depression and overall reduced quality of life. Beyond the myriad major and minor morbidities linked to obesity, increased all-cause mortality and cardiovascular mortality is recognized in the obese. Bariatric surgery literature suggests that, in the morbidly obese, increase in the lifespan is achievable with reversal of obesity, reinforcing the realization that sequelae therein are by no means inevitable. Aggressive efforts must be targeted towards population-based strategies to educate and sensitize all generations on contributors to and sequelae of excess body mass as obesity represents one of the few modifiable factors that impact on the quantity and quality of lifespan., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate patient characteristics and fresh in vitro fertilization (IVF) cycle parameters that influence success of sibling frozen-thawed embryo transfer (FET) cycles., Design: Retrospective study., Setting: Academic infertility practice., Patient(s): Infertile women undergoing FET cycles using embryos cryopreserved on day 3 after insemination after an initial fresh IVF cycle., Intervention(s): 90 FET cycles., Main Outcome Measure(s): Clinical pregnancy (CP)., Result(s): The likelihood of CP after FET was statistically significantly higher in women who had achieved CP in the preceding fresh IVF cycle (71.4% vs. 40.6%). Multivariable logistic regression analysis confirmed that patients achieving CP after the fresh IVF cycle were more likely to achieve CP after FET (OR 5.5; 95% CI, 1.2-25.3) after adjusting for age, number, and cleavage status of embryos transferred. Additionally, higher serum levels of progesterone on the day of human chorionic gonadotropin administration emerged as predictive of CP after FET at a statistically significant level., Conclusion(s): The outcome of the fresh embryo transfer cycle is the foremost predictor of CP after FET of the sibling embryos. The relationship between serum progesterone on the day of human chorionic gonadotropin administration in the fresh cycle and the outcome of subsequent FET is noteworthy and merits further investigation.

To determine whether metformin, when given to women with polycystic ovary syndrome (PCOS), promotes folliculogenesis by prompting a drop in free sex steroids resulting in a compensatory follicle stimulating hormone (FSH) rise, we conducted a randomized, double-blind, placebo-controlled crossover clinical trial. Eight mid-reproductive age PCOS participants with mean obese body mass index (BMI) and normal glucose tolerance received 8 weeks of metformin, given in a step-up fashion to a maximum dose of 2000 mg daily or placebo with daily urine sampling, 4-6 weeks washout, and crossover to the remaining arm for 8 weeks. To confirm the effects of metformin on glucose and other metabolic markers, a hyperinsulinemic, euglycemic 3-dose clamp (physiologic: 30 mU/m(2) per minute, high: 400 mU/m(2) per minute) followed each treatment. Urinary FSH, luteinizing hormone (LH), or pregnanediol glucuronide (Pdg) did not differ by treatment. Glucose disposal, endogenous glucose production, BMI, ovulation rates, serum sex steroids, free fatty acids, and lipids did not significantly differ by treatment, despite good evidence for compliance with the protocol. During the clamp, high-dose insulin administration was associated with an acute drop in serum LH. We conclude that short-term, high-dose metformin exerts minimal effects on both metabolic markers and reproductive hormones in a small sample of overall morbidly obese women.

Objective: To determine whether obesity-related reproductive endocrine abnormalities in ovulatory women are reversible with weight loss., Design: Observational cohort study., Setting: Healthy volunteers in an academic research environment., Patient(s): Women aged 18-48 years with regular menstrual cycles 21-40 days and a body mass index (BMI) >or=35 kg/m(2) planning to undergo bariatric surgery were recruited., Intervention(s): Twenty-five eumenorrheic (non-polycystic ovary syndrome) women with a mean BMI of 47.3 +/- 5.2 kg/m(2) were sampled with daily menstrual cycle urinary hormones before (n = 25) and 6 months after (n = 9) weight loss surgery resulting in >25% reduction of initial body weight. Daily hormones were compared before and after surgery and with 14 normal-weight control subjects., Main Outcome Measure(s): Metabolites of LH, FSH, E(2), and P were measured daily for one menstrual cycle. Group means were compared using t tests among ovulatory cycles., Result(s): Luteal pregnanediol glucuronide (Pdg) increased from 32.8 +/- 10.9 to 73.7 +/- 30.5 microg/mg creatinine (Cr) and whole-cycle LH increased from 168.8 +/- 24.2 to 292.1 +/- 79.6 mIU/mg Cr after surgically induced weight loss. Luteal Pdg remained lower than in normal-weight control subjects (151.7 +/- 111.1 microg/mg Cr). Obese women took longer to attain a postovulatory Pdg rise of >2 microg/mg Cr than control subjects (3.91 +/- 1.51 vs. 1.71 +/- 1.59 days); this improved after surgery (2.4 +/- 1.82 days). Whole-cycle estrone conjugates (E(1c)) was similar to control subjects at baseline, but decreased after weight loss (from 1,026.7 +/- 194.2 to 605.4 +/- 167.1 ng/mg Cr). Follicle-stimulating hormone did not relate to body size in this sample., Conclusion(s): Women of very high BMI have deficient luteal LH and Pdg excretion and a delayed ovulatory Pdg rise compared with normal-weight women. Although these parameters improved with weight loss, Pdg did not approach levels seen in normal-weight women. Luteinizing hormone may be less effective in stimulating the corpus luteum in obesity. The large postoperative decrease in E(1c) may reflect the loss of estrone-producing adipose tissue after weight loss.

Background: In mouse endometrium, glycogen synthase kinase-3beta (GSK3beta) is a key enzyme controlling nuclear localization of cyclin D1. We developed a functional model of xenografted human endometrium to test whether similar mechanisms are operative in the human by using Lithium chloride (LiCl), an inhibitor of GSK3beta., Methods: Human endometrial samples were obtained from normal volunteers, then implanted under the kidney capsule of nude mice, and treated with estradiol-17beta (E2) or LiCl. Xenografts were assessed for protein expression of MKI-67, mini-chromosome maintenance protein-2, estrogen receptor (ER), progesterone receptor (PR) and cyclin D1., Results: Both E2 and LiCl induced a robust proliferative response in the epithelium. Only lithium treatment produced clear nuclear localization of cyclin D1 consistent with the proliferative response observed. Regenerated endometrium had detectable ER and PR expression., Conclusion: Xenografted human endometrium provides a dynamic model of uterine biology. Administration of LiCl in the absence of E2 induced epithelial proliferation, supporting the hypothesis that human and murine endometrial proliferation may share key regulatory pathways. These data suggest a possible link between the increased menstrual disturbances in women with affective disorders taking lithium and the consequent potential for the development of endometrial proliferative disorder.

Nucleolar channel systems (NCSs) are membranous organelles appearing transiently in the epithelial cell nuclei of postovulatory human endometrium. Their characterization and use as markers for a healthy receptive endometrium have been limited because they are only identifiable by electron microscopy. Here we describe the light microscopic detection of NCSs using immunofluorescence. Specifically, the monoclonal nuclear pore complex antibody 414 shows that NCSs are present in about half of all human endometrial epithelial cells but not in any other cell type, tissue or species. Most nuclei contain only a single NCS of uniform 1 microm diameter indicating a tightly controlled organelle. The composition of NCSs is as unique as their structure; they contain only a subset each of the proteins of nuclear pore complexes, inner nuclear membrane, nuclear lamina and endoplasmic reticulum. Validation of our robust NCS detection method on 95 endometrial biopsies defines a 6-day window, days 19-24 (+/-1) of an idealized 28 day cycle, wherein NCSs occur. Therefore, NCSs precede and overlap with the implantation window and serve as potential markers of uterine receptivity. The immunodetection assay, combined with the hitherto underappreciated prevalence of NCSs, now enables simple screening and further molecular and functional dissection.

Objective: To confirm that fever with localized findings is less prevalent among febrile postoperative myomectomy patients than it is among hysterectomy patients., Methods: Hospital records of 341 hysterectomy patients and 250 myomectomy patients were reviewed. Rate of overall febrile morbidity, proportion of fever with localized findings, proportion of febrile patients worked-up, and other perioperative parameters were recorded. Fever was prospectively defined both inclusively (temperature at least 38.0 degrees C occurring at least 4 hours postoperatively) and in standard fashion (temperature at least 38.0 degrees C after 24 hours postoperatively). A localized fever required a positive laboratory, radiologic, or clinical finding. Chi-square, Student t test, and multivariable logistic regression were used., Results: The proportion of patients who developed postoperative fever after at least 4 hours was identical between myomectomy and hysterectomy patients (39.2% compared with 39.3%, P=.98). However, the proportion of febrile myomectomy patients with localized findings was significantly lower than hysterectomy patients (14.3% compared with 31.3%, P=.003). Likewise, when comparing respective rates of overall and localized fever after at least 24 hours postoperatively, similar results were obtained. Multivariable analysis confirmed the lower likelihood of localized findings among febrile postoperative myomectomy patients compared with hysterectomy patients (odds ratio of localized fever 0.30, 95% confidence interval 0.12-0.75, P=.01). Additionally, obesity raised the likelihood of localized findings in each group by 6% per unit of body mass index (odds ratio 1.06, 95% confidence interval 1.01-1.10, P=.03)., Conclusion: Overall postoperative fever rates are similar, but myomectomy is independently associated with fewer localized fevers than hysterectomy. Given the relatively low likelihood of localized fever, clinicians may consider simplifying the fever workup of postoperative myomectomy patients., Level of Evidence: II.

Context: Female obesity is linked to abnormal menstrual cycles, infertility, reproductive wastage, and deficient LH, FSH, and progesterone secretion., Objective and Design: To elucidate the reproductive defects associated with obesity, we sampled 18 eumenorrheic (nonpolycystic ovary syndrome) women with a mean +/- sem body mass index of 48.6 +/- 1.4 kg/m2 with daily, first morning voided urine collections, seven of whom also had early follicular phase 12-h, every 10-min blood sampling to assess LH pulses. Daily hormones were compared with 11 eumenorrheic, normal-weight controls. A separate control group of 12 eumenorrheic, normal-weight women was used for the LH pulse studies., Main Outcome Measures: Assays for LH (serum and urine) and FSH, and estradiol and progesterone metabolites (estrone conjugate and pregnanediol glucuronide; urine) were performed. Daily hormones were meaned and normalized to a 28-d cycle length. LH pulsations were determined using two objective methods. Group means were compared using t tests., Results: Reduced whole-cycle mean, normalized pregnanediol glucuronide was observed in obese (38.2 +/- 2.1 microg/mg creatine) compared with normal-weight women (181.3 +/- 35.1 microg/mg creatine; P = 0.002), without significant differences in LH, FSH, or estrone conjugate. Early follicular phase LH pulse frequency did not differ from normal-weight women, but both amplitude and mean LH were dramatically reduced in obese women (0.8 +/- 0.1 and 2.0 +/- 0.3 IU/liter) compared with controls (1.6 +/- 0.2 and 3.4 +/- 0.2 IU/liter; P < 0.01)., Conclusions: A novel defect in the amplitude but not the frequency of LH pulsations appears to underlie the reproductive phenotype of obesity. The deficit in pregnanediol glucuronide appears to exceed the deficit in LH. The patterns of hypothalamic-pituitary-ovarian axis function unique to the obese state differ from other abnormal reproductive states.

We have recently demonstrated that a short-term treatment of parental splenocytes with the B subunit of cholera toxin (CT-B) abrogates the development of acute GVHD in F1 hybrid mice transplanted with these cells. In order to obtain better insight into the mechanism of the action of CT-B, we studied the effect of CT-B on survival of purified murine T cells and their subsets. We show that treatment with B subunit stimulates apoptosis in T cells, detectable following incubation in vitro. Although apoptosis was noticed in both CD8+ and CD4+ T cell subsets, the treatment preferentially stimulates programmed cell death (PCD) in CD8+ population. Thus, immunosuppressive action of CT-B in vivo may be in part due to its ability to eliminate CD8+ T cells.