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Context: Associations between menstrual cycle length and chronic diseases are hypothesized to be due to differences in underlying hormonal patterns. Objective: The aim of the study was to evaluate the association between menstrual cycle length and the hormonal profile and anovulation. Design and Setting: We conducted a prospective cohort study at the University at Buffalo from 2005 to 2007. Participants: We recruited 259 healthy, regularly menstruating women aged 18–44 yr. Main Outcome Measures: Cycle length was observed for up to two cycles. Serum estradiol, progesterone, LH, and FSH were measured up to eight times per cycle for up to two cycles. Results: Women with short cycles (35 d), estradiol and LH peaks occurred on average about 3 d later, and FSH peaks about 1 d later compared to women with normal-length cycles. Both short and long cycles, compared with normal-length cycles, had an increased probability of anovulation. In general, per-cycle exposure to hormones was less in short cycles based on the area under the curve, although over time the cumulative exposure to estradiol would be greater for women with short cycles. Conclusions: Short ovulatory cycles were associated with higher follicular phase estradiol, an earlier rise in FSH, and an increased risk of anovulation. These results suggest that menstrual cycle length may be a relevant indicator of estradiol exposure and risk of anovulation among regularly cycling women.

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005–2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.

Exposures to cadmium, lead, and mercury are associated with adverse health effects, including cardiovascular disease, which may be promoted by lipid peroxidation. The authors examined cadmium, lead, and mercury in relation to plasma levels of F2-8a isoprostanes (isoprostane), 9-hydroperoxy-10,12-octadecadienoic acid (9-HODE), 13-hydroxy-9,11-octadecadienoic acid (13-HODE), and thiobarbituric acid reactive substances (TBARS) in 252 women from western New York State (2005–2007). Healthy premenopausal women were followed for � 2 menstrual cycles, with biomarkers of lipid peroxidation being assessed � 8 times per cycle. Metals were measured at baseline in whole blood. Linear mixed models were used to estimate the association between cadmium, lead, and mercury and lipid peroxidation biomarkers. Median cadmium, lead, and mercury levels were 0.30 lg/L, 0.86 lg/dL, and 1.10 lg/L, respectively. Blood cadmium, lead, and mercury were not associated with increases in isoprostane, TBARS, 9-HODE, or 13-HODE levels. Isoprostane levels decreased 6.80% (95% confidence interval: � 10.40, � 3.20) per 1% increase in mercury. However, after adjustment for a simulated strong confounding factor, such as precisely measured fish consumption, the observed association was attenuated, suggesting that this unexpected association could be attributable to unmeasured confounding. In this population of healthy premenopausal women with low exposure levels, cadmium, lead, and mercury were not associated with elevated lipid peroxidation biomarkers. cadmium; hydroxyl-octadecadienoic acid; isoprostane; lead; mercury; oxidative stress; thiobarbituric acid reactive substances; women

Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Design: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Results: Caffeine intake 200 mg/d was inversely associated with free estradiol concentrations among white women (b = 20.15; 95% CI: 20.26, 20.05) and positively associated among Asian women (b = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake 1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: b = 0.14 (95% CI: 0.06, 0.22) and b = 0.26 (95% CI: 0.07, 0.45), respectively. Conclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race. Am J Clin Nutr 2012;95:488‐97.

We propose a general framework for performing full Bayesian analysis under linear inequality parameter constraints. The proposal is motivated by the BioCycle Study, a large cohort study of hormone levels of healthy women where certain well-established linear inequality constraints on the log-hormone levels should be accounted for in the statistical inferential procedure. Based on the Minkowski–Weyl decomposition of polyhedral regions, we propose a class of priors that are fully supported on the parameter space with linear inequality constraints, and we fit a Bayesian linear mixed model to the BioCycle data using such a prior. We observe positive associations between estrogen and progesterone levels and F2-isoprostanes, a marker for oxidative stress. These findings are of particular interest to reproductive epidemiologists.

Background: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. Methodology/Principal Findings: The BioCycle study (2005–2007) prospectively followed 259 healthy women aged 18–44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration #5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3 rd tertile of synthetic folate intake had, on average, 16.0% (95% CI, 0.5–33.8%) higher luteal progesterone levels compared to women in the 1 st tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3 rd tertile had a 64% (95% CI, 8–86%) decreased odds of anovulation compared to the women in the 1 st tertile (P trend 0.03). Conclusions/Significance: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted.

Linear mixed-effects models involve fixed effects, random effects and covariance structures, which require model selection to simplify a model and to enhance its interpretability and predictability. In this article, we develop, in the context of linear mixed-effects models, the generalized degrees of freedom and an adaptive model selection procedure defined by a data-driven model complexity penalty. Numerically, the procedure performs well against its competitors not only in selecting fixed effects but in selecting random effects and covariance structure as well. Theoretically, asymptotic optimality of the proposed methodology is established over a class of information criteria. The proposed methodology is applied to the BioCycle Study, to determine predictors of hormone levels among premenopausal women and to assess variation in hormone levels both between and within women across the menstrual cycle.

Understanding variations in lipoprotein cholesterol levels throughout the menstrual cycle is important because there may be clinical implications regarding the appropriate timing of measurement and implications on the design and interpretation of studies in women of reproductive age. Our objective was to review the evidence comparing lipoprotein cholesterol levels throughout the menstrual cycle among premenopausal women. Overall, lipoprotein cholesterol levels were observed to vary in response to changing estrogen levels. Taken together, the evidence suggests that total cholesterol and LDL-C tend to be highest during the follicular phase and to decline during the luteal phase, with HDL C highest around ovulation. Based on these findings, the menstrual cycle phase should be taken into account when evaluating lipoprotein cholesterol levels among reproductive-aged women. Measuring cholesterol levels during menses is recommended for consistent comparisons as this phase can be more reliably identified than other phases, although women within National Cholesterol Education Program acceptable ranges, but near the boundaries when tested during menses, should undergo additional tests.

Reproductive hormone levels are highly variable among premenopausal women during the menstrual cycle. Accurate timing of hormone measurement is essential, especially when investigating day- or phase-specific effects. The BioCycle Study used daily urine home fertility monitors to help detect the luteinising hormone (LH) surge in order to schedule visits with biologically relevant windows of hormonal variability. However, as the LH surge is brief and cycles vary in length, relevant hormonal changes may not align with scheduled visits even when fertility monitors are used. Using monitor data, measurements were reclassified according to biological phase of the menstrual cycle to more accurate cycle phase categories. Longitudinal multiple imputation methods were applied after reclassification if no visit occurred during a given menstrual cycle phase. Reclassified cycles had more clearly defined hormonal profiles, with higher mean peak hormones (up to 141%) and reduced variability (up to 71%). We demonstrate the importance of realigning visits to biologically relevant windows when assessing phase- or day-specific effects and the feasibility of applying longitudinal multiple imputation methods. Our method has applications in settings where missing data may occur over time, where daily blood sampling for hormonal measurements is not feasible, and in other areas where timing is essential.

Objective To define whether anti-Mullerian hormone (AMH) may be a marker of acute cyclophosphamide (CTX)-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix. Design Controlled, experimental study. Setting Research laboratory in a federal research facility. Animal(s) Balb/c female mice (6 weeks old). Intervention(s) Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of CTX or saline control on day 9. Main Outcome Measure(s) Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels. Result(s) Ovaries in mice pretreated with cetrorelix had significantly more PMFs and reduced DNA damage compared with those exposed to CTX alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups. Conclusion(s) Cetrorelix protected PMFs and reduced DNA damage in follicles of mice treated with CTX, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix.

To assess the validity of retrospectively reported maternal behaviors while attempting pregnancy.Participants in a prospective pregnancy cohort study with periconception enrollment were queried about use of cigarettes, alcohol, vitamins and caffeine and the consumption of sport fish while attempting pregnancy. Prospective longitudinal data reported in daily diaries (gold standard) were compared with data obtained a decade later using a self-administered questionnaire. Agreement was assessed by percent agreement and Kappa coefficients.Among the 82 participating women, percent agreement ranged from 54-74% for the 5 behaviors. Validity was highest for smoking (Kappa = 0.43, 95% confidence interval [CI]: 0.22, 0.65) followed by fish consumption (Kappa = 0.32, 95% CI: 0.09, 0.55), caffeine (Kappa = 0.21, 95% CI: 0.09, 0.51) and alcohol (Kappa = 0.20, 95% CI: 0.08, 0.33). There were no systematic differences in agreement by time to pregnancy or pregnancy outcome. Associations between smoking and alcohol consumption and pregnancy outcomes were highly sensitive to the levels of misclassification observed in this study.Validity was poor to moderate for the 5 behaviors, though higher for more regular behaviors such as smoking and caffeine consumption. The potential for misreporting of periconception behaviors can affect inferences, and thus efforts to capture information prospectively should be promoted.

We propose a Bayesian framework for analyzing multivariate linear mixed effect models with linear constraints on the fixed effect parameters. The procedure can incorporate both firm and soft restrictions on the parameters and Bayesian model selection for the random effects. The framework is used to analyze data from the BioCycle study. One of the main objectives of the BioCycle study is to investigate the association between markers of oxidative stress and hormone levels during menstrual cycles of healthy women. Contrary to the popular belief that ovarian hormones are negatively associated with level of F 2-isoprostanes, a known marker for oxidative stress, our analysis finds a positive association between ovarian hormone levels and isoprostane levels. The positive association corroborates the findings from a previous analysis of the BioCycle data. Copyright © 2011 John Wiley & Sons, Ltd.

Outcome-dependent sampling (ODS) study designs are commonly implemented with rare diseases or when prospective studies are infeasible. In longitudinal data settings, when a repeatedly measured binary response is rare, an ODS design can be highly efficient for maximizing statistical information subject to resource limitations that prohibit covariate ascertainment of all observations. This manuscript details an ODS design where individual observations are sampled with probabilities determined by an inexpensive, time-varying auxiliary variable that is related but is not equal to the response. With the goal of validly estimating marginal model parameters based on the resulting biased sample, we propose a semi-parametric, sequential offsetted logistic regressions (SOLR) approach. The SOLR strategy first estimates the relationship between the auxiliary variable and the response and covariate data by using an offsetted logistic regression analysis where the offset is used to adjust for the biased design. Results from the auxiliary variable model are then combined with the known or estimated sampling probabilities to formulate a second offset that is used to correct for the biased design in the ultimate target model relating the longitudinal binary response to covariates. Because the target model offset is estimated with SOLR, we detail asymptotic standard error estimates that account for uncertainty associated with the auxiliary variable model. Motivated by an analysis of the BioCycle Study (Gaskins et al., Effect of daily fiber intake on reproductive function: the BioCycle Study. American Journal of Clinical Nutrition 2009; 90(4): 1061-1069) that aims to describe the relationship between reproductive health (determined by luteinizing hormone levels) and fiber consumption, we examine properties of SOLR estimators and compare them with other common approaches.

Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation.The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18-44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles.Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005).These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome.

Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F(2)-isoprostanes in the BioCycle Study. Women aged 18-44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F(2)-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F(2)-Isoprostane levels had an independent positive association with estradiol (beta = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (beta = -0.04, 95% confidence interval: -0.07, -0.003; beta = -0.02, 95% confidence interval: -0.03, -0.002, respectively) after adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F(2)-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.

In premenopausal women, elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of negative reproductive outcomes. Whole grain consumption has been associated with lower CRP concentrations in older women; however, less is known about this relationship in younger women. We investigated whether whole grain intake was associated with serum high sensitivity CRP (hs-CRP) concentrations in young women. BioCycle was a prospective cohort study conducted at the University of Buffalo from 2005 to 2007, which followed 259 healthy women aged 18–44 y for le 2 menstrual cycles. hs-CRP concentrations were measured longitudinally le 8 times/cycle with visits standardized to menstrual cycle phase. Whole grain intake was estimated by 24-h recalls le 4 times/cycle. Servings were defined as 16 g or 125 mL of a 100% whole grain food. Whole grain intake was inversely associated with hs-CRP concentrations after adjusting for age, race, BMI, illness, and antiinflammatory drug use. Consumers of between 0 and 1 serving/d of whole grains had, on average, 11.5% lower hs-CRP concentrations (P = 0.02) and consumers of ge 1 serving/d had 12.3% lower hs-CRP concentrations (P = 0.02) compared with nonconsumers. Women who consumed ge 1 serving/d of whole grain had a lower probability of having moderate (P = 0.008) or elevated (P = 0.001) hs-CRP according to the AHA criteria compared with nonconsumers. Given that elevated concentrations of hs-CRP have been linked to adverse reproductive outcomes and pregnancy complications, interventions targeting whole grain consumption may have the potential to improve health status among young women.

Objective To determine whether a history of preconceptional dieting and restrained eating was related to higher weight gains in pregnancy. Design Dieting practices were assessed among a prospective cohort of pregnant women using the Revised Restraint Scale. Women were classified on three separate subscales as restrained eaters, dieters, and weight cyclers. Subjects Participants included 1,223 women in the Pregnancy, Infection, and Nutrition Study. Main outcome measures Total gestational weight gain and adequacy of weight gain (ratio of observed/expected weight gain based on Institute of Medicine recommendations). Statistical analyses performed Multiple linear regression was used to model the two weight-gain outcomes, while controlling for potential confounders including physical activity and weight-gain attitudes. Results There was a positive association between each subscale and total weight gain, as well as adequacy of weight gain. Women classified as cyclers gained an average of 2 kg more than noncyclers and showed higher observed/expected ratios by 0.2 units. Among restrained eaters and dieters, there was a differential effect by body mass index. With the exception of underweight women, all other weight status women with a history of dieting or restrained eating gained more weight during pregnancy and had higher adequacy of weight gain ratios. In contrast, underweight women with a history of restrained eating behaviors gained less weight compared to underweight women without those behaviors. Conclusions Restrained eating behaviors were associated with weight gains above the Institute of Medicine's recommendations for normal, overweight, and obese women, and weight gains below the recommendations for underweight women. Excessive gestational weight gain is of concern because of its association with postpartum weight retention. The dietary restraint tool is useful for identifying women who would benefit from nutritional counseling prior to or during pregnancy with regard to achieving targeted weight-gain recommendations.

Objective To evaluate trends in diminished ovarian reserve (DOR) assignment in the Society for Assisted Reproductive Technology (SART) Clinic Outcomes Reporting System database and to evaluate its accuracy in predicting poor ovarian response (POR) as defined in European Society of Human Reproduction and Embryology's Bologna criteria (2011). Design Retrospective cohort study. Setting Not applicable. Patient(s) A total of 181,536 fresh, autologous ART cycles reported to SART by U.S. clinics in 2004 and 2011 (earliest and most recent available reporting years). Intervention(s) None. Main Outcome Measure(s) DOR assignment was the primary exposure. POR, defined as cycle cancellation for poor response or less than 4 oocytes retrieved after conventional gonadotropin stimulation (>149 IU FSH daily), was the primary outcome. Secondary outcomes were live birth and number of oocytes retrieved. DOR prevalence, power of DOR and FSH ( Result(s) DOR prevalence increased from 19% to 26% from 2004 to 2011. Among cycles clinically assigned as DOR, incidence of POR decreased from 32% to 30%, and live birth improved from 15% to 17%. Comparing basal FSH ≥12 versus clinical assignment of DOR, basal FSH had a higher specificity (92.2% vs. 81.6%) and positive predictive value (38.3% vs. 30.9%) for predicting POR. Live birth among POR cycles was 4%. Conclusion(s) DOR diagnosis is increasing, and accuracy remains poor, despite the availability of additional diagnostic parameters such as antral follicle count and antimullerian hormone. POR entailed poor outcomes, but the majority of patients clinically assigned as DOR did not experience POR. Development and use of more accurate predictors of POR are needed to minimize patient distress resulting from overdiagnosis.

timing their pregnancy attempts, were non-smokers without a history of vaginitis, had a cycle length of 28 days, and had normal BMI and were not using hormonal birth control as their last method of conception to about 8% for nulligravid women aged 35 years who have intercourse

Summary Background Preconception-initiated low-dose aspirin might positively affect pregnancy outcomes, but this possibility has not been adequately assessed. Our aim was to investigate whether low-dose aspirin improved livebirth rates in women with one to two previous pregnancy losses. Methods In this multicentre, block-randomised, double-blind, placebo-controlled trial, women aged 18–40 years who were attempting to become pregnant were recruited from four medical centres in the USA. Participants were stratified by eligibility criteria—the original stratum was restricted to women with one loss at less than 20 weeks' gestation during the previous year, whereas the expanded stratum included women with one to two previous losses, with no restrictions on gestational age or time of loss. Women were block-randomised by centre and eligibility stratum in a 1:1 ratio. Preconception-initiated daily low-dose aspirin (81 mg per day) plus folic acid was compared with placebo plus folic acid for up to six menstrual cycles; for women who conceived, study treatment continued until 36 weeks' gestation. Participants, trial staff, and investigators were masked to the assigned treatment. The primary outcome was livebirth rate, which was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00467363. Findings Overall, 1228 women were recruited and randomly assigned between June 15, 2007, and July 15, 2011, 1078 of whom completed the trial and were included in the analysis (535 in the low-dose aspirin group and 543 in the placebo group). 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=0·0984; absolute difference in livebirth rate 5·09% [95% CI −0·84 to 11·02]). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=0·7812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=0·0446; absolute difference in livebirth rate 9·20% [0·51 to 17·89]). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=0·7406; absolute difference in livebirth rate 1·71% [−6·37 to 9·79]). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss. Interpretation Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks' gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (US National Institutes of Health).

To compare cost and efficacy of tubal anastomosis to in vitro fertilization (IVF) in women who desired fertility after a tubal ligation.Cost-effectiveness analysis.Not applicable.Not applicable.Not applicable.Cost per ongoing pregnancy.Cost per ongoing pregnancy for women after tubal anastomosis ranged from $16,446 to $223,482 (2014 USD), whereas IVF ranged from $32,902 to $111,679 (2014 USD). Across maternal age groups35 and 35-40, years tubal anastomosis was more cost effective than IVF for ongoing pregnancy. Sensitivity analyses validated these findings across a wide range of ongoing pregnancy probabilities as well as costs per procedure.Tubal anastomosis was the most cost-effective approach for most women less than 41 years of age, whereas IVF was the most cost-effective approach for women aged ≥41 years who desired fertility after tubal ligation. A model was created that can be modified based on cost and success rates in individual clinics for improved patient counseling.

Objective To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice. Design Decision-tree mathematical model with sensitivity analyses. Setting Not applicable. Patient(s) A simulated cohort of women wishing to delay childbearing until age 40 years. Intervention(s) Not applicable. Main Outcome Measure(s) Cost per live birth. Result(s) Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $55,060 to $39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes. Conclusion(s) In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth.

(1.65 fold). IHC results confirmed reduction of fibronectin protein. COL1A1 and versican IHC analysis is ongoing. CONCLUSION: Our results demonstrate that mifepristone alters ECM formation, reversing the effect of progestin on fibronectin, versican and collagen expression. 3D cultures demonstrate a direct effect on ECMfibrosis. Our findings provide insight into mifepristone mechanism of action which would result in improved therapeutic options for women suffering with symptomatic uterine leiomyomas. Supported by: This research was Supported by Intramural grant from Uniformed Services University of the Health Sciences, QP85GF13 and R21, R085193713.The research was also supported, in part, by the intramural research Program in Reproductive and Adult Endocrinology, NIH.

miscarriages, IVF/PGS (PGS) are increasingly performed in RPL patients with limited clinical evidence. Our objective is to determine if PGS is cost-effective compared to EM in achieving live birth (LB) and preventing clinical miscarriage (CM) for patients with unexplained RPL. DESIGN: A decision analysis of cost incurred and clinical outcomes with PGS versus EM. MATERIALS AND METHODS: A decision-analytic model was constructed using TreeAge Pro 2013. Probabilities for IVF/PGS were derived from published data of outcomes of IVF with 24-chromosome PGS involving 2,282 embryos and 287 PGS cycles followed by fresh embryo transfer (ET) in patients with unexplained RPL. Probabilities for EM were obtained from a prospective longitudinal study of 325 patients with unexplained RPL who underwent clinical evaluation and attempted spontaneous conception with close follow-up. Cost data was obtained from literature and adjusted to 2014 US dollars . For both groups, the average cost of pre-conception counseling and baseline RPL workup including parental karyotyping, maternal anti-phospholipid antibody testing and uterine cavity evaluation was $4,377 . No additional cost was incurred in the EM group. The average cost of IVF with one ET was $18,227 and the average cost of PGS was $4,268 . Cost to achieve live birth and cost to prevent one CM were the primary outcomes of the analysis. In the first model, all patients underwent one PGS cycle and ET, if a euploid embryo was produced. In the second model, patients did a second cycle if they did not conceive with the first. Base case, threshold, and one-way sensitivity analyses and a Monte Carlo simulation were performed to assess the robustness of the model. RESULTS: Cost effectiveness analysis favored EM over PGS. The CP rate per attempt is 35.6% with IVF/PGS compared to 69.5% with EM. Clinical outcomes, cost per LB, and cost to prevent one CM using one and two cycles of PGS compared to EM is shown in Table 1. The model was robust to one-way sensitivity analysis and Monte Carlo simulation.

s / Annals of Epidemiology 24 (2014) 682e702 695 CI, 77.3-79.9) for women 20-59, 28.9% (95% CI, 27.6-30.3) for men from 20-59 and adults older than 59 had a prevalence of 68.6% (95% CI, 67.1-70.2). North and central regions of the country had the highest frequency of central obesity. Conclusions: Central obesity is an important public health problem in Mexico. Our results show that Mexico has higher values of central obesity compared to other countries and the problem is more important in women. Physical activity, nutrition and genetic factor should be taken into account to create health interventions programs according to Mexican population. P54. Impact of Maternal Vitamin D Insufficiency on Neonatal Bone and Fat Mass Nansi Boghossian PhD, MPH, Winston Koo, Aiyi Liu PhD, Sunni Mumford, Kerri Kissell, James Mills, Edwina Yeung PhD. National Institute of Child Health and Human Development Purpose: Conflicting evidence suggests that total maternal 25-hydroxyvitamin D [25(OH)D] is associatedwith fetal bone and fat mass. Associations with the more bioavailable, free 25(OH)D however, have not been investigated. We examined the associations for total and free 25(OH)D with neonatal bone and adiposity by dual-energy x-ray absorptiometry (DXA). Methods: 252 newborns of nulliparous women from theMemphis site of the Calcium for Preeclampsia Prevention trial (1993-1995) underwent DXA within the first week of life. Maternal serum samples, collected 3 times during pregnancy, were measured for 25(OH)D, its binding protein, and albumin fromwhich free 25(OH)D was calculated. Multiple linear regression examined whether maternal total and free 25(OH)D, averaged over pregnancy, were associated with birthweight, neonatal total and lumbar bone mineral content (BMC), bone mineral density (BMD), and fat mass after adjusting for maternal BMI, age, race, smoking status, caloric intake, and serum calcium levels. Results: 63(25%) of the women had Vitamin D insufficiency (

OBJECTIVE: The aim of the study is to analyse the effect of sun exposure as a consequence of lifestyle and outer clothing over bone health in postmenopausal women with normal dual energy x-ray absorptiometry (DEXA). DESIGN: Cross sectional study of 190 postmenopausal women with normal DEXA values of femoral neck and L1-L4 and not taking supplemental Ca or vitamin D. MATERIALS AND METHODS: Blood samples were obtained for 25OHD, calcium, phosphorus, osteocalcin, deoxypyridinoline, thyroid stimulating hormone, HDL, LDL, TG, fasting insulin, fasting glucose, HbA1C, FSH and estradiol levels.Daily sun exposure and lifestyle were questioned for every participant. The examination of femoral neck, total femur and total L1-L4 bone were established with DEXA.Participants were grouped into three categories in relation to daily sun exposure (A: no exposure, B: daily exposure for 10-30 minutes and C: daily exposure more than 30 minutes). The groups were compared with Kruskal-Wallis and posthoc analysis. RESULTS: 25-OHD was found to be higher in group C in comparison to group A(21.96 12.62 vs 12.18 10.96, p1⁄40.005). Deoxypyridinoline was found to be higher in group B in comparison to group C(12.61 3.88 vs 11.17 2.76, p1⁄40.035). Calcium was found to be higher in group C in comparison to group A(9.96 0.41 vs 9.62 0.42, p1⁄40.005). After partial correlation analysis, 25-OHD and calcium were positively and serum deoxypyridinolinewas negatively correlated with daily sun exposure time after adjustment for age and body mass index (r1⁄40.234, p1⁄40.001; r1⁄40.241, p1⁄40.001; r1⁄4-0.157, p1⁄40.031, respectively). CONCLUSION: Exposure to ultraviolet rays in the sunlight through skin is the main source for vitamin D besides the supply from food. Serum 25-hydroxyvitamin D is a good marker for vitamin D which is crucial for calcium and bone metabolism. erum 25-hydroxyvitamin D (25-OHD) and calcium levels are positively and serum deoxypyridinoline levels are negatively correlated with daily sun exposure time after adjustment for age and body mass index in postmenopausal womenwithout osteoporosis. Serum 25-hydroxyvitamin D levels were within the insufficiency range in the postmenopausal population without osteoporosis even in the sun exposure >30 minutes group. Due to nature of a cross sectional we can only demonstrate an association not a cause effect relationship. Further studies with a large population size are required to investigate the relationship between sun exposure and bone health.

Objective To evaluate trends in DOR assignment in the SART CORS database and to evaluate its accuracy in predicting poor ovarian response (POR) as defined in ESHRE’s ‘Bologna Criteria’ (2011).

OBJECTIVE: Although AMH has been studied as a predictor of live birth in assisted reproductive technology (ART), less is known about the association in women with normal fertility. The objective was to assess a possible association between preconception AMH levels with live birth. DESIGN: Secondary analysis of a multicenter, block-randomized, doubleblind, placebo-controlled clinical trial. MATERIALS AND METHODS: 1228 women attempting pregnancy, aged 18–40 years, with one to two prior pregnancy losses and no history of infertility, pelvic inflammatory disease, tubal occlusion, endometriosis, anovulation, uterine abnormality, or polycystic ovarian syndrome were included. Women were block-randomized by center and eligibility stratum in a 1:1 ratio to preconception-initiated daily low-dose aspirin or placebo. The primary outcome was live birth (defined as a living infant born after 23 weeks’ gestation). AMH was assayed using the Gen II ELISA assay (Beckman-Coulter) at the baseline visit before randomization. AMH was clinically categorized and verified by data analysis into low ( 4.0 ng/mL). The Mann Whitney test was utilized to evaluate differences in AMH levels by live birth status. Relative Risk (RR) and 95% confidence intervals (CIs) for live birth by AMH categories were estimated using generalized linear models adjusted for age. RESULTS: Women were followed for up to six menstrual cycles with N1⁄4776 (72%) achieving pregnancy and N1⁄4582 (55%) with a live birth. Women were predominately of white race (95.6%) with a mean age of 28.9 years (standard deviation (SD) 4.7) and body mass index (BMI) of 26.1 (SD 6.5). Among women with a single recent loss, the live birth rate was 53.6% among women with low AMH, 53.9% among normal AMH, and 65.9% among high AMH (p1⁄40.04). After adjusting for age, women with a single recent loss and high (>4.0 ng/mL) AMH levels had an increased risk of live birth (RR1⁄41.2, 95% CI 1.1, 1.4) compared to women with normal levels, whereas women with low AMH (