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Purpose: To evaluate whether underlying infertility and mode of conception are associated with childhood behavioral disorders., Methods: Oversampling on fertility treatment exposure using vital records, the Upstate KIDS Study followed 2057 children (of 1754 mothers) from birth to 11 years. Type of fertility treatment and time to pregnancy (TTP) were self-reported. Mothers completed annual questionnaires reporting symptomology, diagnoses, and medications at 7-11 years of age. The information identified children with probable attention-deficit/hyperactivity disorder, anxiety or depression, and conduct or oppositional defiant disorders. We estimated adjusted relative risks (aRR) for disorders by underlying infertility (TTP > 12 months) or treatment exposure groups compared to children born to parents with TTP ≤ 12 months., Results: Children conceived with fertility treatment (34%) did not have an increased risk of attention-deficit/hyperactivity disorder (aRR): 1.21; 95% CI: 0.88, 1.65), or conduct or oppositional defiant disorders (aRR: 1.31; 0.91, 1.86), but did have an increased risk of anxiety or depression (aRR: 1.63; 1.18, 2.24), which remained elevated even after adjusting for parental mood disorders (aRR: 1.40; 0.99, 1.96). Underlying infertility without the use of treatment was also associated with a risk of anxiety or depression (aRR: 1.82; 95% CI: 0.96, 3.43)., Conclusions: Underlying infertility or its treatment was not associated with risk of attention-deficit/hyperactivity disorder. Observations of increased anxiety or depression require replication., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Currently serving as Associate Editor on Annals of Epidemiology., (Published by Elsevier Inc.)

Study Question: Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?, Summary Answer: Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy., What Is Known Already: Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments., Study Design, Size, Duration: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up., Participants/materials, Setting, Methods: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure., Main Results and the Role of Chance: Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI)., Limitations, Reasons for Caution: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association., Wider Implications of the Findings: Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age., Study Funding/competing Interest(s): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose., Trial Registration Number: N/A., (Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology 2022. This work is written by US Government employees and is in the public domain in the US.)

Objective: To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment., Design: Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment., Setting: New York State (excluding New York City)., Patient(s): This analysis included 855 newborns and 152 children at approximately 9 years of age., Intervention(s): None., Main Outcome Measure(s): DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted., Result(s): Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction., Conclusion(s): ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood., (Published by Elsevier Inc.)

Background: Little is known about the predictors of sexual intercourse frequency (SIF) among couples trying to conceive despite the well-established link between SIF and fecundity., Aim: To evaluate men's and women's demographic, occupational, and lifestyle predictors of SIF among couples., Methods: 469 Couples without a history of infertility participating in the Longitudinal Investigation of Fertility and the Environment Study (2005-2009) were followed up for ≤1 year while trying to conceive. At enrollment, both partners were interviewed about demographic, occupational, lifestyle, and psychological characteristics using standardized questionnaires. Multivariable generalized linear mixed models with Poisson distribution were used to estimate the adjusted percent difference in SIF across exposure categories., Outcomes: SIF was recorded in daily journals and summarized as average SIF/mo., Results: The median (interquartile range) SIF during follow-up was 6 (4-9) acts/mo. For every year increase in age for women and men, SIF decreased by -0.8% (95% CI -2.5 to 1.0%) and -1.7% (95% CI -3.1 to -0.3%). Women with high school education or less and those of non-white race had 34.4% and 16.0% higher SIF, respectively. A similar trend was seen for men's education and race. Only couples where both partners (but not just 1 partner) worked rotating shifts had -39.1% (95% CI -61.0 to -5.0%) lower SIF compared to couples where neither partner worked rotating shifts. Men's (but not women's) exercise was associated with 13.2% (95% CI 1.7-26.0%) higher SIF. Diagnosis of a mood or anxiety disorder in men (but not women) was associated with a 26.0% (95% CI -42.7 to -4.4%) lower SIF. Household income, smoking status, body mass index, night work, alcohol intake, and psychosocial stress were not associated with SIF., Clinical Translation: Even among couples trying to conceive, there was substantial variation in SIF. Both partners' age, education, race, and rotating shift work as well as men's exercise and mental health play an important role in determining SIF., Conclusions: As this was a secondary analysis of an existing study, we lacked information on many pertinent psychological and relationship quality variables and the hormonal status of participants, which could have affected SIF. The unique population-based couple design, however, captured both partners' demographics, occupational characteristics, and lifestyle behaviors in advance of their daily, prospective reporting of SIF, which was a major strength. Important predictors of SIF among couples attempting to conceive include men's exercise and mental health and both partners' age, education, race, and rotating shift work. Gaskins AJ, Sundaram R, Buck Louis GM, et al. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med 2018;15:519-528., (Copyright © 2018 International Society for Sexual Medicine. All rights reserved.)

Study Question: Is couples' body compositions associated with reduced fecundity as measured by a longer time-to-pregnancy (TTP)?, Summary Answer: Couples whose BMI are within obese class II (≥35 kg/m2) have a longer TTP in comparison to leaner (BMI < 25 kg/m2) couples, observed only when both partner's BMI was jointly modeled., What Is Known Already: Extremes of BMI have been associated with a longer TTP and with less successful assisted reproductive technology (ART) outcomes. To our knowledge, the association between measured adiposity in both partners of the couple and prospectively measured TTP has not been investigated despite pregnancy being a couple-dependent outcome., Study Design, Size, Duration: Prospective cohort with preconception recruitment of 501 couples trying for pregnancy and recruited from 16 counties in Michigan and Texas between 2005 and 2009. Couples were followed daily for up to a year of trying or until a hCG pregnancy., Participants/materials, Setting, Methods: In-home standardized anthropometric assessment of couples upon enrollment included measured height and weight using calibrated stadiometers and scales, and measured waist and hip circumferences. Discrete-time Cox regression was used to estimate fecundability odds ratios (FORs) and 95% CIs, controlling for potential confounders including age, number of days of vigorous physical activity, serum cotinine concentration, race, education, free cholesterol levels for each partner in partner-specific models and for both partners in couple-based models as well as average acts of intercourse per menstrual cycle and menstrual cycle regularity., Main Results and the Role of Chance: Neither male nor female partner's BMI was associated with TTP when modeled individually. However, obese class II (BMIs ≥ 35.0 kg/m2) couples experienced a reduction in fecundability in both unadjusted (FOR = 0.45; 95% CI: 0.23, 0.89) and adjusted analyses (aFOR = 0.41; 95% CI: 0.17, 0.98) resulting in a longer TTP in comparison to couples with normal BMI (<25 kg/m2). Female partners' waist circumference ≥88.6 cm was associated with a significant reduction in fecundability in the unadjusted model (FOR = 0.64; 95% CI: 0.48, 0.86) but not in the adjusted model (aFOR = 0.77; 95% CI: 0.55, 1.08) in comparison to females with a smaller (<80 cm) circumference., Limitations, Reasons for Caution: BMI and waist circumference are proxy measures of body composition and residual confounding cannot be eliminated. Findings may not be generalizable to clinical populations., Wider Implications of the Findings: This is the first cohort study known to us with preconception enrollment of couples who underwent standardized anthropometric assessment and for whom TTP was prospectively measured. The findings underscore the importance of considering both partners' body composition for fecundity outcomes and preconception guidance., Study Funding/competing Interest(s): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no competing interests., Trial Registration Number: N/A., (Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We aimed to study the potential impact of proximity to major roadways on time-to-pregnancy and infertility in couples attempting pregnancy in the Longitudinal Investigation of Fertility and Environment (LIFE) study (2005-2009), a population-based, prospective cohort study. Couples attempting pregnancy (n=500) were enrolled and followed prospectively until pregnancy or 12months of trying and 393 couples (78%) had complete data and full follow-up. Time-to-pregnancy was based on a standard protocol using fertility monitors, tracking estrone-3-glucuonide and luteinizing hormone, and pregnancy test kits to detect human chorionic gonadotropin (hCG). The fecundability odds ratio (FOR) and 95% confidence interval (CI) were estimated using proportional odds models. Infertility was defined as 12months of trying to conceive without an hCG pregnancy and the relative risk (RR) and 95% CI were estimated with log-binomial regression. Final models were adjusted for age, parity, study site, and salivary alpha-amylase, a stress marker. Infertile couples (53/393; 14%) tended to live closer to major roadways on average than fertile couples (689m vs. 843m, respectively) but the difference was not statistically significant. The likelihood of pregnancy was increased 3% for every 200m further away the couples residence was from a major roadway (FOR=1.03; CI=1.01-1.06). Infertility also appeared elevated at moderate distances compared to 1000m or greater, but estimates lacked precision. Our findings suggest that proximity to major roadways may be related to reductions in fecundity. Prospective data from larger populations is warranted to corroborate these findings., (Published by Elsevier B.V.)

Introduction: Previous studies suggest female smoking increases time-to-pregnancy (TTP), a couple-dependent reproductive outcome, while associations with male smoking are more ambiguous. Furthermore, despite small increases in smokeless tobacco use in the United States, no prior study has evaluated TTP among smokeless tobacco users., Methods: Using population-based sampling in 16 counties in Michigan and Texas, 501 couples discontinuing contraception to become pregnant were followed until positive pregnancy test or 12 months of trying. Participants were interviewed on lifetime and current cigarette, cigar, and chew/snuff (smokeless) use and provided blood samples for quantification of heavy metals and cotinine. Fecundability odds ratios (FORs) and 95% confidence intervals (95% CIs) were estimated, adjusted for demographics/lifestyle. FORs less than 1 reflect longer TTP., Results: Eleven percentage of females and 15% of males smoked cigarettes. Among men, 14% smoked cigars, 9% used snuff, and 2% used chew. Compared with never tobacco users, male (FOR: 0.41, 95% CI: 0.24, 0.68) and female (FOR: 0.53, 95% CI: 0.33, 0.85) smoking were individually associated with longer TTP; males' smoking remained significant (FOR: 0.46, 95% CI: 0.27, 0.79) when modeling partners together. Cadmium levels were higher in smokers than smokeless tobacco and never users; adjusting for cadmium attenuated the cigarette-TTP association, particularly among women. TTP was shorter among smokeless tobacco users relative to smokers (FOR: 2.86, 95% CI: 1.47, 5.57)., Conclusions: Compared with never users, smokeless tobacco did not alter TTP in our cohort; however, TTP was shorter compared with smokers. We observed longer TTP in male and female smokers; cadmium may partially contribute., Implications: Both partners' preconception smoking contributed to longer TTP, highlighting the importance of both partners' lifestyles in healthy reproduction and underscores the need for couple-based preconception guidance. The male's contribution is a new finding. Higher cadmium levels may partially contribute to longer TTP in smokers, particularly among females. Though we do not observe longer TTP among a small sample of smokeless tobacco users compared with never tobacco users, we observe shorter TTP compared with smokers. Further work is needed to more thoroughly delineate the relationship between smokeless tobacco use and TTP and possible mechanisms of tobacco use's effects on reproduction., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The analysis of fecundity data is challenging and requires consideration of both highly timed and interrelated biologic processes in the context of essential behaviors such as sexual intercourse during the fertile window. Understanding human fecundity is further complicated by presence of a sterile population, i.e. couples unable to achieve pregnancy. Modeling techniques conducted to date have largely relied upon discrete time-to-pregnancy survival or day-specific probability models to estimate the determinants of time-to-pregnancy or acute effects, respectively. We developed a class of semi-parametric grouped transformation cure models that capture day-level variates purported to affect the cycle-level hazards of conception and, possibly, sterility. Our model's performance is assessed using simulation and longitudinal data from one of the few prospective cohort studies with preconception enrollment of women followed for 12 menstrual cycles at risk for pregnancy., (© The Author(s) 2012.)

ObjectiveTo identify frequently reported prescription medications and supplements among couples planning pregnancy because there is a lack of descriptive information on these agents in women and men who are trying to conceive.MethodsFive hundred one couples enrolled in the Longitudinal Study of Infertility and the Environment, which took place between 2005 and 2009. Participants reported prescription medications as well as prescription and over-the-counter supplements used through interviews at study enrollment and through daily dairies during the 12-month follow-up. We identified prescription medications and supplements prospectively reported by ≥1% of women and men at baseline and from daily journal information grouped into 3-month preconception follow-up intervals while couples tried for pregnancy.ResultsThe 5 most reported prescription medications among women were levothyroxine (5.8%), cetirizine (2.6%), fluticasone (2.4%), escitalopram (1.8%), and fluoxetine (1.8%) and for men were lisinopril (2.0%), mometasone (2.0%), fexofenadine (1.8%), atorvastatin (1.6%), and montelukast (1.6%). The most reported supplements were multivitamins (63.3%, 43.5%) and fish oil (13.2%, 9.4%) for women and men, respectively, and prenatal vitamins (22.0%) for women. For women during the first 3 months of follow-up, prenatal vitamins (6.0%) and antibiotics (1.2%-2.6%) were among the most frequently started medications. During the next 3 months, clomiphene (4.5%) was the most frequently initiated medication.ConclusionsCouples trying for pregnancy reported a variety of prescription medications and supplements, and they differed by gender. Preconception guidance should address medication and supplement use to avoid potential exposures associated with adverse reproductive and perinatal outcomes.

Endometriosis, ectopic growth of the uterine lining (endometrium), which affects 6-11% of reproductive age women, is associated with pelvic pain and infertility. We investigated the peritoneal fluid (PF), urine and omental fat (OF) proteomes of women with endometriosis vs. individuals with no surgically visualized endometriosis. All participants were enrolled in the NICHD-funded ENDO Study. A two-step proteomic study was performed. The first, a broad survey, employed a semi-quantitative gel LC-mass spectrometry (MS) workflow: SDS PAGE fractionation, trypsin digestion and LC-MS/MS. The results showed sample integrity but failed to detect any differences between women with and without endometriosis. The second step was a quantitative analysis of OF samples. We employed another sample set (n=30) from women ± disease and isobaric mass-tag (iTRAQ) chemistry to label peptides and 2D LC-MS/MS for protein identification and quantification. Three proteins-matrix metalloproteinase-9, neutrophil elastase, and FAM49B-were significantly lower in abundance in samples from women with endometriosis. Interestingly, neutrophil elastase and FAM49B levels were associated with higher levels of a subset of endocrine disrupting chemicals (EDCs) that were previously measured in the same samples. The results of these experiments showed the feasibility of associating endometriosis with changes in the OF protein repertoire and EDC levels.Biological significanceEndometriosis, pathological growth of the uterine lining, is associated with significant morbidities, including pain and infertility. However, the causes of this common condition are poorly understood. This study determined whether endometriosis was associated with changes in the protein composition of peritoneal fluid, urine and/or omental fat. A protein of unknown function (FAM49B) and two proteinases (metalloproteinase-9, neutrophil elastase) were down regulated in OF samples from women with versus without endometriosis. These findings suggested proteinase imbalances at sites that were distant from the endometriotic lesions. Additionally, FAM49B and neutrophil elastase levels were associated with higher levels of a subset of environmental chemicals that were quantified in the same samples, suggesting other possible associations. Thus, this work generated hypotheses that will be tested in further studies.

BACKGROUND: Human exposure to parabens and other antimicrobial chemicals is continual and pervasive. The hormone-disrupting properties of these environmental chemicals may adversely affect human reproduction. OBJECTIVE: We aimed to prospectively assess couples' urinary concentrations of antimicrobial chemicals in the context of fecundity, measured as time to pregnancy (TTP). METHODS: In a prospective cohort of 501 couples, we examined preconception urinary chemical concentrations of parabens, triclosan and triclorcarban in relation to TTP; chemical concentrations were modeled both continuously and in quartiles. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) adjusting for a priori-defined confounders. In light of TTP being a couple-dependent outcome, both partner and couple-based exposure models were analyzed. In all models, FOR estimates < 1.0 denote diminished fecundity (longer TTP). RESULTS: Overall, 347 (69%) couples became pregnant. The highest quartile of female urinary methyl paraben (MP) concentrations relative to the lowest reflected a 34% reduction in fecundity (aFOR = 0.66; 95% CI: 0.45, 0.97) and remained so when accounting for couples' concentrations (aFOR = 0.63; 95% CI: 0.41, 0.96). Similar associations were observed between ethyl paraben (EP) and couple fecundity for both partner and couple-based models (p-trend = 0.02 and p-trend = 0.05, respectively). No associations were observed with couple fecundity when chemicals were modeled continuously. CONCLUSIONS: Higher quartiles of preconception urinary concentrations of MP and EP among female partners were associated with reduced couple fecundity in partner-specific and couple-based exposure models. CITATION: Smarr MM, Sundaram R, Honda M, Kannan K, Buck Louis GM. 2016. Urinary concentrations of parabens and other antimicrobial chemicals and their association with couples' fecundity. Environ Health Perspect 124:730-736; http://dx.doi.org/10.1289/EHP189 [ABSTRACT FROM AUTHOR]

Study Question: What is the relationship between couple's health and fecundity in a preconception cohort?Summary Answer: Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).What Is Already Known: The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.Study Design, Size, Duration: A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.Participants/materials, Settings, Methods: In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Main Results and the Role Of Chance: Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.Limitations, Reasons For Caution: The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.Wider Implications Of the Findings: The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Study Funding/competing Interests: Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters, given their use in sunscreen and personal-care products and their reported estrogenic and antiandrogenic activity. We recruited 501 couples who were discontinuing use of contraceptives in order to become pregnant for the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (Michigan and Texas, 2005–2009). Couples provided urine specimens and completed daily journals until they either achieved pregnancy or had tried for 12 months. Women used fertility monitors to time sexual intercourse and digital pregnancy tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP-1); 2,2′,4,4′-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2′-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone. Fecundability odds ratios were estimated for each UV filter (dichotomized at the 75th percentile) and adjusted for age, creatinine concentration, body mass index (weight (kg)/height (m)2), cotinine concentration, season, and site, while accounting for time off contraception. Separate models were fitted for each UV filter and partner; final models included partners' concentrations. Male partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95% confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00), respectively). In models adjusting for both partners' concentrations, male BP-2 concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI: 0.49, 0.97). These data suggest that male exposure to select UV filters may diminish couples' fecundity, resulting in a longer time to pregnancy. [ABSTRACT FROM PUBLISHER]

Background Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. Methods We utilised the Upstate New York livebirth registry ( n = 201 063) to select births conceived with ( n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without ( n = 14 455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. Results Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies ( ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly ( P < 0.01) earlier gestations than unexposed infants (38.3 ± 2.8 and 38.7 ± 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 ± 2.7 and 38.7 ± 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 ± 704 and 3194 ± 679 g, respectively), but differed using maternal report (3167 ± 692 and 3224 ± 661, respectively P < 0.05). Conclusions The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings. [ABSTRACT FROM AUTHOR]

Abstract Background Novel methodologies to quantify infant exposures to endocrine disrupting chemicals (EDCs) for population-based studies are needed. Objectives We used newborn dried blood spots to quantify three EDCs and their associations with infant outcomes in the Upstate KIDS Cohort. Methods We measured bisphenol A (BPA), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in 2071 singleton and 1040 twin infants born to mothers in New York State. We log transformed concentrations after rescaling by their standard deviations and modeled each in relation to gestational age, birthweight, length, head circumference and Ponderal Index (PI) using linear regression techniques. All models were adjusted for maternal age, body mass index, education, infertility treatment and parity. Generalized estimating equations with robust standard errors were used to assess the associations for twins. Results Chemicals were largely quantified above the limits of detection (>99% for PFOS and PFOA; 90% for BPA). Overall, we observed no significant associations between PFASs and birth size irrespective of plurality of birth. However, among twins, BPA was associated with decreases in gestational age (adjusted β = −0.09 weeks; 95% Confidence Interval (CI): −0.16, −0.02) and birthweight (adjusted β = −32.52 g; 95% CI: −60.99, −4.05), head circumference (adjusted β = −0.18 cm; 95% CI: −0.38, −0.02) and increased PI in singletons (adjusted β = 0.02 cm; 95% CI: 0.004, 0.04). Conclusion We observed negative associations between BPA and birth size in twins. Our findings demonstrate the feasibility of newborn dried blood spots for quantifying neonatal exposure at the population level. Highlights • Used newborn dried blood spots to quantify BPA, PFOS and PFOA • Observed inverse association between BPA and birth size in twins • No observed association between BPA and birth size in singletons • No observed association with PFOS and PFOA and birth size, regardless of plurality [ABSTRACT FROM AUTHOR]

Objective To assess the validity of maternally reported assisted reproductive technologies (ART) use and to identify predictors of reporting errors. Design Linkage study. Setting Not applicable. Patient(s) A total of 5,034 (27%) mothers enrolled, from whom 4,886 (97%) self-reported information about use of infertility treatment, including ART, for the index birth. Intervention(s) None. Main Outcome Measure(s) Four measures of validity (sensitivity, specificity, positive and negative predictive values) and use of net reclassification improvement (NRI) methods to identify predictors associated with concordant/discordant maternal reporting. Result(s) The Upstate New York Infant Development Screening Program (Update KIDS Study) was linked with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) using a defined algorithm for 2008–2010. The sensitivity, specificity, positive and negative predictive values were high (0.93, 0.99, 0.80, and 1.00, respectively). The validity of maternal report was high, reflecting few differences by participant characteristics except for maternal age dichotomized at 29 years as identified with NRI methods. Conclusion(s) Maternally reported ART is valid, with little variation across various characteristics. No strong predictors of discordant reporting were found, supporting the utility of population-based research with SART CORS linkage. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of infertility using a current duration approach for comparison with a traditional constructed measure. Design: Cross-sectional survey. Setting: Not applicable. Patient(s): A nationally representative sample of females aged 15–44 years. Intervention(s): None. Main Outcome Measure(s): Infertility prevalence estimated by two approaches: [1] a constructed measure derived from questions on sexual activity, contraception, relationship status, and pregnancy, and [2] a measure based on estimated time to pregnancy derived from the respondents’ current duration of pregnancy attempt (i.e., current duration approach). Associations with self-reported descriptive characteristics using weighted logistic regression or parametric survival models for each respective approach. Result(s): Infertility prevalence was approximately twofold higher using the current duration approach (15.5%; 95% confidence interval 8.6%–27.5%) vs. the constructed measure (7.0%; 95% confidence interval 6.2%–7.8%). Both methods identified similar patterns of increasing age, lower education, nulliparity, and history of gynecologic disorders as being associated with measures of impaired fecundity, whereas opposing patterns were seen for racial/ethnic identification and poverty status. Conclusion(s): Infertility prevalence based on a current duration approach was consistent with other US prospective cohort studies with preconception enrollment. These findings underscore the importance of definition and methodologic approach for estimating the prevalence of infertility. [ABSTRACT FROM AUTHOR]