Paternal mixtures of urinary concentrations of phthalate metabolites, bisphenol A and parabens in relation to pregnancy outcomes among couples attending a fertility center

• Type of Material: Article
• Authors: Lidia Mínguez-Alarcón, Harvard T.H. Chan School of Public Health; Andrea Bellavia, Harvard T.H. Chan School of Public Health; Audrey Gaskins, Emory University; Jorge E Chavarro, Harvard T.H. Chan School of Public Health; Jennifer B Ford, Harvard T.H. Chan School of Public Health; Irene Souter, Massachusetts General Hospital; Antonia M Calafat, Centers for Disease Control and Prevention, Atlanta; Russ Hauser, Harvard T.H. Chan School of Public Health; Paige L Williams, Harvard T.H. Chan School of Public Health
• Language: English
• Date: 2021-01-01
• Publisher: PERGAMON-ELSEVIER SCIENCE LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 The Author(s). Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envint.2020.106171
• Title of Journal or Parent Work: ENVIRONMENT INTERNATIONAL
• Volume: 146
• Start Page: 106171
• End Page: 106171
• Grant/Funding Information: The project was funded by grants R01ES022955, R01ES009718, R01ES028800 and by grant P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). AJG was supported by R00ES026648.
• Keywords: INFERTILITY; ASSOCIATION; EPIGENETIC INHERITANCE; QUANTIFICATION; VITRO FERTILIZATION OUTCOMES; REPRODUCTIVE OUTCOMES; Science & Technology; WOMEN; Parabens; Pregnancy outcomes; Bisphenol A; Survival analysis; Environmental Sciences & Ecology; LIFE-STYLE; HEALTH; Life Sciences & Biomedicine; Phthalates; Environmental Sciences; PRENATAL EXPOSURE; Paternal chemical mixtures

Abstract

Background: Few epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples’ pregnancy outcomes. Objective: We investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center. Methods: We included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed. Results: We identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores. Conclusion: Paternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.