The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments.
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ABSTRACT:
SUBMITTER: Souter I
PROVIDER: S-EPMC4383527 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
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The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments.
Souter Irene I Smith Kristen W KW Dimitriadis Irene I Ehrlich Shelley S Williams Paige L PL Calafat Antonia M AM Hauser Russ R
Reproductive toxicology (Elmsford, N.Y.) 20131004
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=114) a ...[more]
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Project description:BackgroundPhthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF).MethodsWe collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (< 35 years) and an older group (≥ 35 years) to explore the potential effect modification by age. We also performed sensitivity analyses by restricting our analyses to only infertile women diagnosed with tubal factor infertility to test the robustness of the results.ResultsSignificant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses.ConclusionWe found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.
| S-EPMC10801055 | biostudies-literature
Project description:ObjectiveTo determine whether infertile women have lower antral follicle counts (AFC) than age-matched normal women.DesignCase-control.SettingAcademic center.Patient(s)A total of 881 infertile women and 771 women from the community.Intervention(s)Antral follicle count and basal hormone measurements.Main outcome measure(s)Median AFCs and FSH levels were compared between the two groups within 5-year age strata by using the median test. A subanalysis was performed by identifying women in the control group with a history of attempting conception without success (subfertile group) and with a spontaneous conception in fewer than 12 months resulting in a live birth (fertile group). Age-specific AFC percentiles were calculated and compared within strata determined by age at the time of attempted conception.Result(s)AFCs were significantly lower in infertile women than in control women across age groups up to 40 years of age. Average FSH levels were significantly higher in the younger-age infertile group versus the community. AFC percentiles differ significantly between fertile and subfertile women within the community up to 40 years of age.Conclusion(s)Decreased AFC in infertile women suggests that factors affecting the size of the remaining follicle pool in younger women also affect oocyte quality and the likelihood of conception.
| S-EPMC3080442 | biostudies-literature
Project description:Human exposure to bisphenol A (BPA) is widespread. Animal studies have demonstrated that BPA can alter endocrine function, but human studies are limited. For the present study, we measured urinary BPA concentrations and serum thyroid and reproductive hormone levels in 167 men recruited through an infertility clinic. BPA was detected in 89% of urine samples with a median (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted for potential confounders, BPA concentrations in urine collected on the same day as a blood sample were inversely associated with serum levels of inhibin B and estradiol:testosterone ratio (E(2):T) and positively associated with follicle-stimulating hormone (FSH) and FSH:inhibin B ratio. Because BPA is metabolized quickly and multiple urine measures may better reflect exposure than a single measure, we also considered among a subset of the men the BPA concentrations in repeated urine samples collected weeks or months following serum sample collection. In these analyses, the effect estimates remained consistent for FSH and E(2):T but were somewhat weakened for inhibin B. In addition, we observed inverse relationships between urinary BPA concentrations and free androgen index (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid stimulating hormone. Our results suggest that urinary BPA concentrations may be associated with altered hormone levels in men, but these findings need to be substantiated through further research.
| S-EPMC2823133 | biostudies-literature
Project description:Benzophenone-3 is used in a variety of cosmetic products as a sunscreen, and has shown weak estrogenic and antiandrogenic activity in animal and in vitro studies. Few studies have evaluated whether benzophenone-3 is associated with reproductive outcomes among women. We studied 304 women undergoing infertility treatment (2007-2017) in the prospective Environment and Reproductive Health cohort study and who underwent 449 treatment cycles (n = 788 urines). Generalized linear mixed models were used with random intercepts to account for multiple cycles, and adjusting for confounders including physical activity. Analyses were also stratified by self-reported moderate/heavy outdoor work. The cycle-specific median (IQR) urinary benzophenone-3 concentration was 147 (58, 462) μg/L, and 98% samples had detectable concentrations. Self-reported sunscreen use, physical activity, and time spent on moderate/heavy outdoor work were positively associated with urinary benzophenone-3. Adjusted probabilities of implantation, clinical pregnancy and live birth were higher in increasing quartiles of benzophenone-3, but these associations were restricted to women who reported spending time outdoors performing moderate/heavy work. Specifically, among these women, those in the highest quartile of benzophenone-3 concentrations had 51% higher implantation (p,trend = 0.02), 68% higher clinical pregnancy (p,trend = 0.01) and 75% higher live birth (p,trend = 0.02) adjusted probabilities than women in the lowest quartile. Benzophenone-3 was unrelated to these outcomes among women who did not report doing moderate/heavy work outdoors. These results confirm that sunscreen use is a source of benzophenone-3 exposure, and show positive associations between benzophenone-3 and pregnancy outcomes, especially among women who reported engaging in outdoor work. Since these associations may be subject to important residual confounding by lifestyle factors, further research is needed to confirm these novel results in other populations, and to investigate whether other factors may be affecting the relation of benzophenone-3 with fertility and other health outcomes.
| S-EPMC6550292 | biostudies-literature
Project description:Study questionAre urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting?Summary answerHigher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care.What is known alreadyExperimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown.Study design, size, durationWe examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study.Participants/materials, setting, methodsWe quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking.Main results and the role of chanceWe observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24% (95% confidence interval (CI): -32%, -16%), -19% (95% CI: -27%, -9%), and -14% (95% CI: -23%, -5%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95% CI: 13.2, 15.2) compared with 10.7 follicles (95% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated.Limitations, reasons for cautionWe demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals.Wider implications of the findingsEnvironmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development.Study funding/competing interestsWork supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.
| S-EPMC4677966 | biostudies-literature
Project description:We examined the patterns, variability, and predictors of urinary bisphenol A (BPA) concentrations in 337 children from the Cincinnati, Ohio HOME Study. From 2003 to 2014, we collected two urine samples from women at 16 and 26 weeks of pregnancy and six urine samples from children at 1-5 and 8 years of age. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) as a measure of within-person BPA variability and to identify sociodemographic and environmental predictors. For the 8-year visit, we used multivariable linear regression to explore associations between urinary BPA concentrations and exposure-related factors. We calculated daily intakes using equations estimating creatinine excretion rates and creatinine-standardized BPA concentrations. Urinary BPA concentrations, which decreased over childhood, had a low degree of reproducibility (ICC < 0.2). Estimated daily intakes decreased with age and were below the reference dose of 50 μg/kg body weight/day. BPA concentrations were positively associated with consuming food stored or heated in plastic, consuming canned food and beverages, and handling cash register receipts. Our results suggest that there are multiple sources of BPA exposure in young children. Etiological studies should collect serial urine samples to accurately classify BPA exposure and consider sociodemographic and environmental factors as possible confounders.
| S-EPMC5547574 | biostudies-literature
Project description:BACKGROUND:We have previously investigated whether urinary concentrations of bisphenol A (BPA), parabens, and phthalate metabolites were individually associated with reproductive outcomes among women undergoing in vitro fertilization (IVF) treatment. However, humans are typically exposed to many man-made chemicals simultaneously. Thus, investigating one chemical at a time may not represent the effect of mixtures. OBJECTIVE:To investigate whether urinary concentrations of BPA, parabens, and phthalate metabolite mixtures are associated with reproductive outcomes among women undergoing IVF. METHODS:This prospective cohort study included 420 women contributing 648 IVF cycles who provided up to two urine samples per cycle prior to oocyte retrieval (N = 1145) between 2006 and 2017 at the Massachusetts General Hospital Fertility Center, and had available urine biomarker data. Urinary concentrations of BPA, parabens, and phthalate metabolites were quantified using isotope-dilution tandem mass spectrometry. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were used to identify main patterns of BPA, parabens, and phthalate metabolites concentrations. We used generalized linear mixed models to evaluate the association between PCA-derived factor scores, in quartiles, and IVF outcomes, using random intercepts to account for multiple IVF cycles and adjusting for known confounders. Because of temporal trends in exposure, we conducted a sensitivity analysis restricted to women who underwent IVF cycles in the earlier years of study (2006-2012). RESULTS:Urinary concentrations of BPA, parabens, and most phthalate metabolites were significantly lower during the second half of the study period (2013-2017) than during the first half (2006-2012). None of the three factors derived from the PCA [di(2-ethylhexyl) phthalate (DEHP), non-DEHP, and paraben] was associated with IVF outcomes in the main analyses. Similarly, BKRM analyses did not identify any associations of individual urinary concentrations of BPA, paraben and phthalate metabolites with IVF outcomes while accounting for correlation between exposures. However, in sensitivity analyses restricted to women who underwent IVF cycles from 2006 to 2012, where concentrations of most phthalates and phenols were higher, there were decreases in implantation, clinical pregnancy, and live birth across quartiles of the DEHP factor. Specifically, women in the highest quartile of the DEHP factor had, on average, lower probabilities of implantation (-22% p, trend = 0.08), clinical pregnancy (-24% p, trend = 0.14), and live birth (-38% p, trend = 0.06) compared to women in the lowest quartile. Among this group of women, BKMR results did not identify any single contributor driving the decreased probabilities of live birth within the DEHP factor. CONCLUSIONS:We confirmed that women undergoing IVF are concurrently exposed to multiple endocrine disrupting chemicals (EDCs). While we found no overall significant associations, we observed diminished pregnancy success with specific clusters of chemicals among women who underwent IVF cycles in earlier years of study, when urinary concentrations of these EDCs were higher.
| S-EPMC6469504 | biostudies-literature
Project description:This study was aimed to evaluate the association between urinary bisphenol A (BPA) levels and risk of obesity in Korean adults. We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012-2014) and Cycle 3 (2015-2017). A total of 10,021 participants aged ≥ 19 years were included. Urine dilution was corrected by the covariate-adjusted standardization (CAS) method. We performed meta-analysis, logistic regression analysis by matching all covariates with a 1:1 propensity score, and a 4-knot restricted cubic spline plot model to calculate the odds ratios (ORs) for obesity according to natural log-transformed BPA levels. Mean urinary BPA concentration was 1.12 µg/L in KoNEHS Cycle 2 and 1.32 µg/L in Cycle 3. BPA levels were significantly higher among obese adults than among non-obese adults in both KoNEHS Cycles 2 and 3. In pooled data of KoNEHS Cycles 2 and 3, BPA showed significant positive associations with ORs for obesity in both sexes, which were more prominent in females (linear) than in males (non-linear). These associations were confirmed in spline analyses. CAS-applied BPA concentrations were positively associated with obesity in nationwide representative samples of Korean adults. Further studies are warranted to confirm and elucidate the underlying mechanism.
| S-EPMC7811011 | biostudies-literature
Project description:Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.
| S-EPMC4408490 | biostudies-literature
Project description:With limited research focusing on non-persistent chemicals as exogenous factors affecting human sex selection, this study aimed to evaluate the association of urinary bisphenol A (BPA) and phthalate metabolite concentrations with the secondary sex ratio (SSR), defined as the ratio of male to female live births. The current analysis is limited to singleton live births (n=220, 43.9%) from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, in which couples discontinuing contraception with the intention of becoming pregnant were enrolled and followed while trying for pregnancy and through delivery for those achieving pregnancy. Using modified Poisson regression models accounting for potential confounders, we estimated the relative risks (RRs) of a male birth per standard deviation change in the log-transformed maternal, paternal, and couple urinary BPA and 14 phthalate metabolite concentrations (ng/mL) measured upon enrollment. When maternal and paternal chemical concentrations were modeled jointly, paternal BPA (RR, 0.77; 95% confidence interval [CI], 0.62-0.95) and mono-isobutyl phthalate (RR, 0.82; 95% CI, 0.67-1.00) were significantly associated with a female excess. Contrarily, maternal BPA (RR, 1.16; 95% CI, 1.03-1.31), mono-isobutyl phthalate (RR, 1.28; 95% CI, 1.06-1.54), mono-benzyl phthalate (RR, 1.31; 95% CI, 1.08-1.58), and mono-n-butyl phthalate (RR, 1.24; 95% CI, 1.01-1.51) were significantly associated with a male excess. These findings underscore varying patterns for the SSR in relation to parental exposures. Given the absence of previous investigation, these partner-specific associations of non-persistent chemicals with the SSR need future corroboration.
| S-EPMC4355045 | biostudies-literature