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Preconception counseling is recommended for all women with diabetes starting at puberty to convey the importance of optimal diabetes management for maternal and fetal outcomes. This study included 622 female participants from the SEARCH for Diabetes in Youth study with a mean age of 22.2 years (range 14–35 years). Only 53.7% reported ever receiving preconception counseling, which was significantly lower among women seeing pediatric providers than those seeing adult or all-age providers. Older age and history of prior pregnancy were associated with increased odds of reporting having received preconception counseling. Identification of barriers to delivering preconception counseling to young females with diabetes and strategies to overcome them are needed to reduce the risk for pregnancy complications and adverse offspring health outcomes.

We investigate the spatiotemporal dynamics and control of an epidemic using a partial differential equation (PDE) based Susceptible-Latent-Infected-Recovered (SLIR) model. We first validate the model using empirical COVID-19 data corresponding to a period of 45 days from the state of Ohio, United States. Upon optimizing the model parameters in the learning phase of the analysis using actual infection data from a period of the first 30 days, we then find that the model output closely tracks the actual data for the next 15 days. Next, we introduce a control input into the model to represent the Non-Pharmaceutical Intervention of social distancing. Implementing the control using two distinct schemes, we find that in both cases the control input is able to significantly mitigate the infection spread. In addition to opening a novel pathway towards the characterization, analysis and implementation of Non-Pharmaceutical Interventions across multiple geographical scales using Control frameworks, our results highlight the importance of first-principles based PDE models in understanding the spatiotemporal dynamics of epidemics triggered by novel pathogens.

We study the spatiotemporal dynamics of an epidemic spread using a compartmentalized PDE model. The model is validated using COVID-19 data from Hamilton County, Ohio, USA. The model parameters are estimated using a month of recorded data and then used to forecast the infection spread over the next ten days. The model is able to accurately estimate the key dynamic characteristics of COVID-19 spread in the county. Additionally, a stability analysis indicates that the model is robust to disturbances and perturbations which, for instance, could be used to represent the effects of super spreader events. We also use the modeling framework to analyse and discuss the impact of Non-pharmaceutical interventions (NPIs) for mitigation of infection. Our results suggest that such models can yield useful short and medium term predictive characterization of an epidemic spread in a restricted geographical region and also help formulate effective NPIs for mitigation. The results also signify the importance of further research into the accurate analytical representation of specific NPIs and hence their dampening effects on an infection spread.

Background Although donor milk is increasingly fed to preterm infants, the resultant quality of growth and body composition is unknown. The aim of this pilot study was to describe the body composition of very low-birth-weight infants fed human milk in the neonatal intensive care unit and explore the association between the proportion of donor human milk intake and fat-free and fat mass deposition. Methods Body composition of 30 preterm infants fed maternal and donor human milk was measured by air displacement plethysmography. Regression models were developed to associate each parameter of body composition with the proportion of donor milk intake and other explanatory variables. Results The proportion of donor milk intake was negatively associated with body fat percentage (P = .01). Fat-free mass z-scores ranged from -4.6 to 1.11 (mean z-score of -0.95, 17th percentile). Conclusion Donor human milk intake is negatively associated with body fat percentage in this pilot study of very low-birth-weight preterm infants.

Background Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) are effective for weight loss in adolescents with severe obesity. However, little is known about adverse gastrointestinal symptoms (GIS) following these operations in adolescents. The objective was to examine GIS over 5 years after surgery and differences by surgery type. Methods We prospectively studied 228 adolescents (161 RYGB, 67 VSG) undergoing bariatric surgery. Gastrointestinal symptoms were assessed before surgery, at 6-months, and yearly to 5 years after surgery. Symptom severity was dichotomized for analysis. Analysis of post-surgery symptoms involved linear models adjusting for baseline symptoms, BMI, early post-operative complication, sex, and race. Results Participants at surgery were 17 ± 1.6 years with preoperative BMI 53 ± 9.4 kg/m2. From 6 months to 5 years, gastroesophageal reflux symptoms (GERS), nausea, bloating, and diarrhea increased. Crude prevalence rates of GERS increased from 4% (1% RYGB, 11% VSG) at 6-months post-surgery to 14% (10% RYGB, 26% VSG) at 5-years. In adjusted analyses, the VSG group experienced 4-fold (4.85 95% CI 2.63, 8.91, p Conclusions Adolescents who underwent VSG experienced greater risk of GERS compared to those undergoing RYGB. Adolescents undergoing VSG should be counseled preoperatively about GERS and objectively monitored postoperatively for gastroesophageal reflux when indicated. Clinical trial registration ClinicalTrials.gov , Identifier: NCT00474318 , https://clinicaltrials.gov/ct2/show/NCT00474318?term=Teen-LABS&rank=1 . Type of Study Treatment Study. Level of Evidence Level II.

OBJECTIVE To identify correlates of hemoglobin A1c (HbA1c) testing frequency and associations with HbA1c levels and microvascular complications in youth-onset diabetes. RESEARCH DESIGN AND METHODS The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years (n = 1,885 type 1, n = 230 type 2) and 13 years (n = 649 type 1, n = 84 type 2) diabetes duration. We identified correlates of reporting ≥3 HbA1c tests/year using logistic regression. We examined associations of HbA1c testing with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression. RESULTS For type 1 diabetes, odds of reporting ≥3 HbA1c tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (odds ratio [OR] 0.91 [95% CI 0.88–0.95]), longer duration of diabetes (OR 0.90 [0.82–0.99]), not having a personal doctor (OR 0.44 [0.30–0.65]), and lapses in health insurance (OR 0.51 [0.27–0.96]). HbA1c testing ≥3 times/year over time was associated with lower HbA1c levels (OR −0.36% [−0.65 to −0.06]) and lower odds of microvascular complications (OR 0.64 [0.43–0.97]) at 13 years’ duration, but associations were attenuated after adjustment for HbA1c testing correlates (OR −0.17 [−0.46 to 0.13] and 0.70 [0.46–1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased the odds of reporting ≥3 HbA1c tests/year over time (OR 0.19 [0.06–0.63]), but HbA1c testing frequency was not associated with HbA1c levels or microvascular complications. CONCLUSIONS We observed disparities in HbA1c testing frequency predominately by health care–related factors, which were associated with diabetes outcomes in type 1 diabetes.

Objective To identify correlates of hemoglobin A1c (HbA1c) testing frequency and associations with HbA1c levels and microvascular complications in youth-onset diabetes. Research Design and Methods The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years diabetes duration (n=1,885 type 1, n=230 type 2) and 13 years duration (n=649 type 1, n=84 type 2). We identified correlates of reporting ≥3 HbA1c tests/year using logistic regression. We examined associations of HbA1c testing with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression. Results For type 1 diabetes, odds of reporting ≥3 HbA1c tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (OR 0.91 [95%CI 0.88-0.95]), longer duration of diabetes (OR 0.90 [0.82-0.99]), not having a personal doctor (0.44 [0.30-0.65]), and lapses in health insurance (OR 0.51 [0.27-0.96]). HbA1c testing ≥3 times/year over time was associated with lower HbA1c levels (-0.36% [-0.65 to -0.06]) and lower odds of microvascular complications (OR 0.64 [0.43-0.97]) at 13 years duration, but associations were attenuated after adjustment for HbA1c testing correlates (-0.17 [-0.46 to 0.13]); OR 0.70 [0.46-1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased odds of reporting ≥3 HbA1c tests/year over time (OR 0.19 [0.06-0.63]), but HbA1c testing frequency was not associated with HbA1c levels or microvascular complications. Conclusions We observed disparities in HbA1c testing frequency, predominately by healthcare-related factors, which were associated with diabetes outcomes in type 1 diabetes.

OBJECTIVE Over the past few decades, life expectancy in Brazil has increased from 48 years in 1950s to 76 years in 2017. The aim of this study was to investigate the impact of ageing on: (1) the frequency of hospitalisations due to bloodstream infection (BSI); (2) the incidence of hospital-acquired BSI (H-BSI); (3) the incidence of BSI caused by multidrug-resistant (MDR) agents and (4) the mortality rate of BSI in a public hospital. METHODS A hospital-based case-cohort study was conducted between 1 December 2013 and 31 December 2015. The data were analysed using multivariable logistic regression. RESULTS A total of 500 BSI episodes were detected, among 11,102 hospitalizations. The incidence of hospitalisations resulting from BSI was significantly higher in older than younger patients (3.7/100 vs. 2.0/100, p

Hemoglobin A1c (HbA1c) monitoring over time is thought to facilitate care and support diabetes management goals, but only half of youth and young adults with diabetes report ≥3 HbA1c tests/year despite poor glycemic control. We explored disparities in HbA1c testing over time and association with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) in the SEARCH for Diabetes in Youth study. Individuals diagnosed with diabetes at In conclusion, we report that mainly healthcare-related factors are associated with disparities in HbA1c testing frequency over time in youth-onset type 1 and type 2 diabetes, and these disparities are associated with HbA1c levels in type 1 diabetes. Disclosure K. A. Sauder: None. R. Dagostino: Consultant; Self; AstraZeneca, Biogen, Daiichi Sankyo. D. Dabelea: None. J. M. Stafford: None. S. R. Ehrlich: None. A. D. Liese: None. S. M. Marcovina: None. A. K. Mottl: Advisory Panel; Self; Bayer U. S. C. Pihoker: None. S. Saydah: None. A. S. Shah: None. Funding National Institutes of Health; Centers for Disease Control and Prevention

Exposure to maternal diabetes in utero increases the risk in the offspring for a range of metabolic disturbances. However, the timing and variability of in utero hyperglycemic exposure necessary to cause impairment have not been elucidated. The TEAM Study was initiated to evaluate young adult offspring of mothers with pregestational diabetes mellitus. This paper outlines the unique enrollment challenges of the TEAM Study and preliminary analysis of the association between exposure to diabetes in pregnancy and adverse metabolic outcomes. The TEAM Study enrolls offspring of women who participated in a Diabetes in Pregnancy (DiP) Program Project Grant between 1978 and 1995. The DiP Study collected medical and obstetric data across pregnancy. The first 96 eligible offspring of women with pregestational diabetes were age-, sex-, and race-matched to adults from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 with an OGTT. Descriptive and regression analyses were employed to compare TEAM participants to NHANES participants. Among a subset of TEAM participants, we compared the metabolic outcomes across maternal glucose profiles using a longitudinal data clustering technique that characterizes level and variability, in maternal glucose across pregnancy. By comparing categories of BMI, TEAM Study participants had over 2.0 times the odds of being obese compared to matched NHANES participants (for class III obesity, OR = 2.81 ; 95% confidence interval (CI): 1.15, 6.87). Increasing levels of two-hour glucose were also associated with in utero exposure to pregestational diabetes in matched analyses. Exposure to pregestational diabetes in utero may be associated with an increased risk of metabolic impairment in the offspring with clinical implications.

We investigate the spatiotemporal dynamics and control of an epidemic using a partial differential equation (PDE) based Susceptible-Latent-Infected-Recovered (SLIR) model. We first validate the model using empirical COVID-19 data corresponding to a period of 45 days from the state of Ohio, United States. Upon optimizing the model parameters in the learning phase of the analysis using actual infection data from a period of the first 30 days, we then find that the model output closely tracks the actual data for the next 15 days. Next, we introduce a control input into the model to represent the Non-Pharmaceutical Intervention of social distancing. Implementing the control using two distinct schemes, we find that in both cases the control input is able to significantly mitigate the infection spread. In addition to opening a novel pathway towards the characterization, analysis and implementation of Non-Pharmaceutical Interventions across multiple geographical scales using Control frameworks, our results highlight the importance of first-principles based PDE models in understanding the spatiotemporal dynamics of epidemics triggered by novel pathogens.

Exposure to poly- and perfluoroalkyl substances (PFAS), ubiquitous and persistent environmental contaminants, could be associated with adverse health outcomes, but there are limited longitudinal data assessing patterns and predictors of exposure during childhood. We quantified concentrations of eight different PFAS in sera collected from women during pregnancy and children at delivery and ages 3 and 8 years in 367 mother-child pairs enrolled in a prospective cohort from 2003 to 2006. In general, median childhood PFAS concentrations increased from birth to age 3 and then decreased by age 8. Maternal serum PFAS concentrations during pregnancy were strongly correlated with cord serum concentrations (0.76 r 0.94), but were weakly correlated with childhood concentrations (0.12 r 0.30). Several sociodemographic factors were associated with maternal PFAS concentrations, including income, race, and parity. In children, serum PFAS concentrations were associated with maternal age at delivery, race, parity, and child age. Breastfeeding duration was positively associated with childhood PFAS concentrations at ages 3 and 8 years. In addition, stain repellant use was associated with higher perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations at age 8 years. Serum PFAS concentrations are higher during early childhood, a potentially sensitive period of development, and were highest among breastfed children.

Objective To examine the incidence of postoperative neonatal acute kidney injury (AKI) following general surgical procedures and to test the hypothesis that postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations predict AKI. The secondary objective was to evaluate for an association between AKI and hospital mortality. Study design Prospective observational study of infants undergoing abdominal and thoracic surgical procedures in the neonatal intensive care unit from October 2018 to March 2020. The primary outcome was incidence of neonatal AKI (defined by the neonatal modified Kidney Diseases Improving Global Outcomes criteria) following each procedure to postoperative day 5. Severe AKI was defined as stage 2 or 3 AKI. Urine samples were obtained pre- and postoperatively at 6 time points to evaluate for levels of uNGAL. Secondary outcomes were in-hospital mortality and length of stay. Results Subjects (n = 141) underwent a total of 192 general surgical procedures during the study period. Neonatal AKI and severe AKI occurred following 36 (18%) and 15 (8%) procedures (n = 33 subjects). Percent change of uNGAL from 24 hours preoperatively to 24 hours postoperatively was greater in subjects with neonatal AKI (190.2% [IQR 0.0, 1666.7%] vs 0.7% [IQR -31.2%,140.2%], P = .0374). The strongest association of uNGAL and AKI occurred at 24 hours postoperatively (area under the receiver operator curves of 0.81, 95% CI 0.72, 0.89). Increased mortality risk was observed in subjects with any postoperative AKI (aOR 11.1 95% CI 2.0, 62.8, P = .0063) and severe AKI (aOR 13.8; 95% CI 3.0, 63.1, P = .0007). Conclusion Elevation in uNGAL 24 hours postoperative was associated with AKI. Neonates with postoperative AKI had increased mortality.

Obesity is identified as a major global health problem. Along with measuring body mass index (BMI), the most common metric for defining weight status, health related quality of life (HRQol) has been accepted as a routine method to evaluate how body weight may be impacted by psychosocial factors. The objective of the current study is to characterize the joint association of change in longitudinal BMI and HRQol following metabolic and bariatric surgery and to examine the correlation between these two outcomes measured concurrently over time. We identified the optimal modeling strategy by comparing four models, all of which involved the covariance structures appropriate for correlated outcomes, BMI and HRQol in a repeated measures analysis. The bivariate random effects models performed better than the univariate random effects models. Moreover, bivariate models with composite covariate structures had better model fit compared to the bivariate random slope models. The bivariate models with composite covariate structures reflected that changes in HRQol (and BMI) were most significant during the first 6 months, a clinically useful window to monitor changes in post-operative HRQol and BMI, and if there might need to be additional interventions or at least, closer monitoring.

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association.

Objectives The purpose of this study is to evaluate the prevalence, impact, and interaction of short interpregnancy interval (IPI), pre-pregnancy body mass index (BMI) category, and pregnancy weight gain (PWG) on the rate of preterm birth. Methods This is a population-based retrospective cohort study using vital statistics birth records from 2006 to 2011 in OH, US, analyzing singleton live births to multiparous mothers with recorded IPI (n = 393,441). Preterm birth rate at

Objective To determine the association between placental weight (PW) and large for gestational age (LGA) in women with type 1 diabetes mellitus (T1DM) and whether glycemic control modifies the association. Study Design In a retrospective analysis of a cohort of women with T1DM, poor glycemic control was defined as glycohemoglobin A1(HbA1)≥ 8.5% (≥2 standard deviations [SD] above mean), and LGA as birth weight > 90th percentile, according to gestation, race, and sex. Multivariable logistic regression was used for analysis. Stratified analyses (HbA1

BACKGROUND: Prenatal perfluoroalkyl substance (PFAS) exposure has been associated with reduced birth weight and excess child adiposity, but the relationship between PFAS and early life growth is unknown. OBJECTIVE: To determine if prenatal PFAS exposure was associated with birth weight, body composition and growth until 2 years of age. METHODS: In a prospective cohort of women and their children from Cincinnati, OH, we quantified perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in pregnant women’s serum. We used linear regression to estimate associations of PFAS with birth weight z-scores (n=345) and linear mixed models to estimate associations with repeated weight and length/height measurements (n=334) at ages 4 weeks and 1 and 2 years, after adjusting for sociodemographic, perinatal, nutritional, and environmental factors. RESULTS: We found non-significant inverse associations between PFAS and infant birth weight. For example, each log(2) increase in PFOA was associated with a 0.03 standard deviation reduction in birth weight z-score (95% CI:−0.17, 0.10). Compared to associations with birth weight, we observed stronger associations between PFAS and child anthropometry from 4 weeks to 2 years. For instance, each log(2) increase in PFOA was associated with a 0.12 standard deviation decrease in BMI z-score (95% CI: −0.25, 0.01). We did not observe any differences in growth rate associated with PFAS. CONCLUSION: We observed inverse associations between prenatal serum PFAS concentrations and anthropometry until age 2 years. Prenatal serum PFAS concentrations were not associated with growth rate in the first 2 years of life.

Changing demographic trends and projections of the survival and fertility rates of each generation have been a topic of great interest to not only demographers and epidemiologists but also to evolutionary biologists and reproductive endocrinologists. Compelling evolutionary theories suggest that there is an inverse association between fertility and longevity. Multiple historic, demographic, and current studies have since been conducted to test this theory, but the results have been inconclusive. The average number of children born to each woman has been declining progressively in developed countries during recent decades. This is in part due to changes in the behavior of couples but also to environmental factors. While improved accessibility to assisted reproductive technology can relieve some of the burden of infertility on these couples and lessen the problem of low total fertility rates in many developed countries, it is not enough to overcome the overall decrease in total fertility rates that we have witnessed in recent decades. This article critically reviews some important studies and provides an overview of this ongoing debate, while highlighting the relevance of trying to understand the possible mechanisms that may link fertility and infertility to longevity.

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62 ppm, range: 0.03-5.66 ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate.

In epidemiological research, it has become increasingly important to assess subjects’ exposure to different classes of chemicals in multiple environmental media. It is a common practice to aliquot limited volumes of samples into smaller quantities for specific trace level chemical analyses. A novel method was developed for the determination of 14 perfluorinated alkyl acids (PFAAs) in small volumes (10 mL) of drinking water using off-line solid phase extraction (SPE) pre-treatment followed by on-line pre-concentration on a WAX column before analysis on column-switching high performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS). In general, large volumes (100–1000 mL) have been used for the analysis of PFAAs in drinking water. The current method requires approximately 10 mL of drinking water concentrated by using an SPE cartridge and eluted with methanol. A large volume injection of the extract was introduced on to a column-switching HPLC–MS/MS using a mix-mode SPE column for the trace level analysis of PFAAs in water. The recoveries for most of the analytes in the fortified laboratory blanks ranged from 73 ± 14% to 128 ± 5%. The lowest concentration minimum reporting levels (LCMRL) for the 14 PFAAs ranged from 0.59 to 3.4 ng/L. The optimized method was applied to a pilot-scale analysis of a subset of drinking water samples from an epidemiological study. These samples were collected directly from the taps in the households of Ohio and Northern Kentucky, United States and the sources of drinking water samples are both surface water and ground water, and supplied by different water distribution facilities. Only five PFAAs, perfluoro-1-butanesulfonic acid (PFBS), perfluoro-1- -hexanesulfonic acid (PFHxS), perfluoro-1-octanesulfonic acid (PFOS), perfluoro-n-heptanoic acid (PFHpA) and perfluoro-n-octanoic acid (PFOA) are detected above the LCMRL values. The median concentrations of these five PFAAs detected in the samples was ≤4.1 ng/L with PFOS at 7.6 ng/L and PFOA at 10 ng/L. Concentrations of perfluoro-1-decanesulfonic acid, PFDS and other perfluoroalkyl carboxylic acids were below the LCMRL values.

In this prospective cohort of women undergoing infertility treatments, we measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used regression models to evaluate the association of BPA with antral follicle count (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume (OV). BPA, detected in >80% of women, had a geometric mean (±GSD) of 1.6±2.0, 1.7±2.1, and 1.5±1.8µg/L for the women contributing to the AFC (n=154), day-3 FSH (n=120), and OV (n=1 14) analyses, respectively. There was an average decrease in AFC of 12% (95% CI: −23%, −0.6%), 22% (95% CI: −31%, −11%), and 17% (95% CI: −27%, −6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st quartile, respectively (p-trend

Exposure to bisphenol A (BPA), a chemical widely used in consumer products, has been associated with in vitro Cyp19 gene expression.To evaluate an in vivo human model of Cyp19 gene expression in granulosa cells.A subset of an ongoing prospective cohort study of women undergoing in vitro fertilization (IVF) at Massachusetts General Hospital.Mixed effect models were used to evaluate the association of urinary BPA concentrations with granulosa cell Cyp19 mRNA expression.In 61 women undergoing 76 IVF cycles, adjusted changes in mean Cyp19 expression (β estimate (95% CI)) for quartiles 2, 3 and 4 as compared to the lowest quartile were: -0.97 (-2.22, 0.28); -0.97 (-2.18, 0.24) and -0.38 (-1.58, 0.82).An in vivo model for evaluation of Cyp19 gene expression was developed for use in epidemiologic studies. In this pilot study, we found no statistically significant linear association between urinary BPA concentrations and Cyp19 expression.

Background: Parabens are preservatives commonly used in personal care products, pharmaceuticals, and foods. There is documented widespread human exposure to parabens, and some experimental data suggest that they act as estrogenic endocrine disruptors. As far as we are aware, no epidemiologic studies have assessed female reproductive health effects in relation to paraben exposure. Objective: We examined the association of urinary paraben concentrations with markers of ovarian reserve in a prospective cohort study of women seeking fertility treatment at Massachusetts General Hospital, Boston, Massachusetts. Methods: Measures of ovarian reserve were day-3 follicle-stimulating hormone (FSH), antral follicle count (AFC), and ovarian volume. Paraben concentrations [methylparaben (MP), propylparaben (PP), and butylparaben (BP)] were measured in spot urine samples collected prior to the assessment of outcome measures. We used linear and Poisson regression models to estimate associations of urinary paraben concentrations (in tertiles) with ovarian reserve measures. Results: Of the women enrolled in 2004–2010, 192 had at least one ovarian reserve outcome measured (mean age ± SD, 36.1 ± 4.5 years; range, 21.0–46.7 years). MP and PP were detected in > 99% of urine samples and BP in > 75%. We found a suggestive trend of lower AFC with increasing urinary PP tertiles [mean percent change (95% CI) for tertiles 2 and 3 compared with tertile 1, respectively, were –5.0% (–23.7, 18.4) and –16.3% (–30.8, 1.3); trend p-value (ptrend) = 0.07] as well as higher day-3 FSH with higher urinary PP tertiles [mean change (95% CI) for tertiles 2 and 3 compared with tertile 1 were 1.16 IU/L (–0.26, 2.57) and 1.02 IU/L (–0.40, 2.43); ptrend = 0.16]. We found no consistent evidence of associations between urinary MP or BP and day-3 FSH or AFC, or between urinary MP, PP, or BP and ovarian volume. Conclusions: PP may be associated with diminished ovarian reserve. However, our results require confirmation in further studies. Citation: Smith KW, Souter I, Dimitriadis I, Ehrlich S, Williams PL, Calafat AM, Hauser R. 2013. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect 121:1299–1305; http://dx.doi.org/10.1289/ehp.1205350

Objective This study aims to evaluate the association between prepregnancy body mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes mellitus (DM). Methods This is a secondary analysis of a cohort of 426 pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women were categorized according to prepregnancy BMI: low BMI ( Results Low BMI was associated with preterm delivery. High BMI was associated with emergent delivery for maternal indications. Glycemic control as measured by glycohemoglobin A1 was associated with increased risk of spontaneous abortion, attenuating the association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk factor to be considered when caring for women with type 1 DM, in particular for preterm delivery (low BMI) and emergent delivery for maternal indications (high BMI).

Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant.This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number.Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32).A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). Methods: We used online solid phase extraction–high performance liquid chromatography–isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval. Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). Conclusion: There was a positive linear dose–response association between BPA urinary concentrations and implantation failure.

Objective To assess the relation between body mass index (BMI) and short-term weight change with assisted reproductive technology (ART) outcomes. Design Prospective cohort study. Setting Fertility center. Patient(s) A total of 170 women undergoing 233 ART cycles. Intervention(s) Baseline BMI and short-term weight change were related to ART outcomes. Regression models accounting for repeated observations were used to adjust data for potential confounders. Main Outcome Measure(s) Peak E2 levels, oocyte yield, MII yield, fertilization rate, embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates. Result(s) Overweight and obesity were associated with lower live birth rates. The adjusted live birth rate (95% confidence interval) was 42% (28%–58%) among women with a BMI between 20 and 22.4 kg/m 2 and 23% (14%–36%) among overweight or obese women. Short-term weight loss was associated with a higher proportion of metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91% (87%–94%) for women who lost 3 kg or more and 86% (81%–89%) for women whose weight remained stable. This association was stronger among women who were overweight or obese at baseline. Short-term weight loss was unrelated to positive β-hCG, clinical pregnancy, or live birth rates. Conclusion(s) Overweight and obesity were related to lower live birth rates in women undergoing ART. Short-term weight loss was related to higher MII yield, particularly among overweight and obese women, but unrelated to clinical outcomes.

Background: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive. Objective: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003. Methods: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders. Results: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2–3.4) for PCB-153 and 1.7 (1.0–2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450–inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found. Conclusions: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs.

To estimate whether alcohol use at the initiation of an in vitro fertilization (IVF) cycle is associated with IVF outcomes.In this prospective cohort study, men and women completed a self-administered questionnaire before their first IVF cycle. Participants reported alcohol type, amount, and frequency consumed. Discrete survival analysis was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) for live birth-the primary outcome. Secondary outcomes were cycle characteristics and points of failure in the IVF process (cycle cancellation, failed fertilization, implantation failure, and spontaneous abortion). We conducted multicycle analyses with final models adjusted for potential confounders that included cycle number, cigarette use, body mass index, and age.A total of 2,545 couples contributed 4,729 cycles. Forty-one percent of women and 58% of men drank one to six drinks per week. Women drinking at least four drinks per week had 16% less odds of a live birth rate compared with those who drank fewer than four drinks per week (OR 0.84, CI 0.71-0.99). For couples in which both partners drank at least four drinks per week, the odds of live birth were 21% lower compared with couples in which both drank fewer than four drinks per week (OR 0.79; CI 0.66-0.96).Consumption of as few as four alcoholic drinks per week is associated with a decrease in IVF live birth rate.II.

Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8 – 2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI –40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed.

Bisphenol A (BPA) is a synthetic chemical used in the manufacture of materials present in many common consumer products. In experimental animals, BPA caused oocyte aneuploidy and reduced production of oestradiol. In a prospective cohort study, we investigated the association between urinary BPA concentrations and ovarian response among women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital (MGH) Fertility Center. The geometric mean of two specific-gravity (SG) adjusted urinary BPA concentrations collected during each IVF cycle was used as the cycle-specific BPA exposure level. BPA concentrations were measured using online solid phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. Peak serum oestradiol was measured using the Elecsys Estradiol II immunoassay kit. Multivariable mixed effect models and Poisson regression models adjusting for correlation between multiple IVF cycles in the same woman were used to evaluate the association between urinary BPA concentrations and ovarian response, adjusting for age, BMI and day 3 follicle stimulating hormone (FSH) levels, a clinical measure of ovarian reserve. Urinary BPA concentrations were measured in 84 women (mean age 35.6 years) undergoing 112 IVF cycles; 23 women (27%) contributed more than one IVF cycle. BPA concentrations ranged from

Background Bisphenol A (BPA) has been linked to changes in the dopamine system and development of an Attention-Deficit/Hyperactivity Disorder (ADHD) phenotype in animal models, with differing effects in males compared to females. We examined the association between urinary BPA concentrations and ADHD in a national sample of U.S. children, and whether this association differs by child sex. Methods We used data from the 2003–2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the U.S. population. Participants were 8-15 years of age (N=460). Using a diagnostic interview to ascertain the presence of ADHD in the past year, multivariable logistic regression examined the link between concurrent urinary BPA concentrations and ADHD status. Results Of the 460 participants, 7.1% [95% CI: 4.4–11.3] met Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) criteria for ADHD. Children who had BPA concentrations at or above the median of the sample had higher prevalence of meeting criteria for ADHD (11.2% [95% CI: 6.8–17.8]) than those with BPA concentrations below the median (2.9% [95% CI: 1.1–7.2]). Higher urinary BPA concentrations were associated with ADHD (adjusted odds ratio [aOR]: 5.68 [95% CI: 1.6–19.8] for BPA concentrations above vs. below the median). In sex-stratified analyses, these associations were stronger in boys (aOR=10.9 [95% CI: 1.4–86.0]) than in girls (aOR=2.8 [95% CI: 0.4–21.3]), although the BPA by sex interaction term was not significant (p=0.25). Conclusion We found evidence that higher urinary BPA concentrations were associated with ADHD in U.S. children; these associations were stronger in boys than in girls. Considering the widespread use of BPA and growing literature on neurobehavioral effects of BPA in children, further study is warranted to determine if reducing exposure to BPA may represent an important avenue for ADHD prevention.

STUDY QUESTION Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE The specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (

Background: In 2007, an expert panel reviewed associations between bisphenol A (BPA) exposure and reproductive health outcomes. Since then, new studies have been conducted on the impact of BPA on reproduction. Objective: In this review, we summarize data obtained since 2007, focusing on a) findings from human and animal studies, b) the effects of BPA on a variety of reproductive end points, and c) mechanisms of BPA action. Methods: We reviewed the literature published from 2007 to 2013 using a PubMed search based on keywords related to BPA and male and female reproduction. Discussion: Because BPA has been reported to affect the onset of meiosis in both animal and in vitro models, interfere with germ cell nest breakdown in animal models, accelerate follicle transition in several animal species, alter steroidogenesis in multiple animal models and women, and reduce oocyte quality in animal models and women undergoing in vitro fertilization (IVF), we consider it an ovarian toxicant. In addition, strong evidence suggests that BPA is a uterine toxicant because it impaired uterine endometrial proliferation, decreased uterine receptivity, and increased implantation failure in animal models. BPA exposure may be associated with adverse birth outcomes, hyperandrogenism, sexual dysfunction, and impaired implantation in humans, but additional studies are required to confirm these associations. Studies also suggest that BPA may be a testicular toxicant in animal models, but the data in humans are equivocal. Finally, insufficient evidence exists regarding effects of BPA on the oviduct, the placenta, and pubertal development. Conclusion: Based on reports that BPA impacts female reproduction and has the potential to affect male reproductive systems in humans and animals, we conclude that BPA is a reproductive toxicant. Citation: Peretz J, Vrooman L, Ricke WA, Hunt PA, Ehrlich S, Hauser R, Padmanabhan V, Taylor HS, Swan SH, VandeVoort CA, Flaws JA. 2014. Bisphenol A and reproductive health: update of experimental and human evidence, 2007–2013. Environ Health Perspect 122:775–786; http://dx.doi.org/10.1289/ehp.1307728

Objective To assess the influence of inadequate birth spacing on birth timing distribution across gestation. Design Population-based retrospective cohort study using vital statistics birth records. Setting Ohio, USA. Study Population Singleton, non-anomalous live births ≥20 weeks to multiparous mothers, 2006–2011. Methods Birth frequency at each gestational week was compared following short IPIs of

Background: Human exposure to bisphenol A (BPA) is widespread and of high public health concern due to associations with adverse health outcomes. Exposure is primarily through diet and consumption ...

Background Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant. Methods This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0–12.3) in the ART group and 9.3 years (interquartile range 8.0–10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number. Results Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80–1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22–31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67–6.32). Conclusion A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation?Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation.Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development.Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis.Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations.The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08).Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample.The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF.This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests.The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Background: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy. Objective: We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure. Methods: We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure. Results: Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA. Conclusions: Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended.

Background: Hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE) are persistent chlorinated pesticides with endocrine activity that may adversely affect the early stages of human reproduction. Objective: Our goal was to determine the association of serum levels of HCB, DDT, and DDE with implantation failure, chemical pregnancy, and spontaneous abortion in women undergoing in vitro fertilization (IVF) from 1994 to 2003. Methods: Levels of HCB and congeners of DDT and DDE were measured in serum collected during the follicular phase. Multivariable-adjusted statistical models accommodating multiple outcomes and multiple cycles per woman were used to estimate the relation between serum pesticide levels and IVF outcomes. Results: A total of 720 women with a mean ± SD age 35.4 ± 4.2 years at enrollment contributed 774 IVF cycles. All samples had detectable levels of HCB, DDT, and DDE, with median levels of 0.087 ng/g serum for HCB, 1.12 ng/g serum for total DDT, and 1.04 ng/g serum for p,p´-DDE. Compared with the lowest quartile (Q1) of HCB, the lipid- and multivariable-adjusted odds ratio (OR) for failed implantation was significantly elevated for those with higher HCB quartiles [Q2–Q4; adjusted ORs: for Q2, 1.71; 95% confidence interval (CI): 1.03, 2.82; for Q3, 2.30; 95% CI: 1.39, 3.81; for Q4, 2.32; 95% CI: 1.38, 3.90] and showed a significantly increasing trend (p = 0.001). No statistically significant associations were observed between DDT/DDE and IVF outcomes or between HCB and chemical pregnancy or spontaneous abortion. Conclusions: Serum HCB concentrations were on average lower than that of the general U.S. population and associated with failed implantation among women undergoing IVF.