Urinary concentrations of non-persistent endocrine disrupting chemicals and fecundability in a preconception cohort study

Background and aim: Non-persistent endocrine-disrupting chemicals (EDCs) are found in consumer products including personal care products, plastics, and cleaning supplies. EDCs can affect hormonal pathways involved in reproduction. We examined prospectively the association between urinary concentrations of select non-persistent EDCs and fecundability, the per cycle probability of conception. Methods: We used data from PRESTO and Snart Foraeldre.dk, web-based preconception cohort studies that recruited female participants who were aged 21-45 years, residents of North America or Denmark, and trying to conceive without fertility treatment (2013-2019). Participants completed a baseline questionnaire and follow-up questionnaires every 8 weeks for up to 12 months. A subset of 207 participants residing in Boston, Massachusetts (n=119), Detroit, Michigan (n=18), or Aalborg, Denmark (n=70) provided urine samples during in-person clinic visits. We measured concentrations of 7 phenols, 4 parabens, triclocarban, 15 phthalate metabolites and 2 phthalate alternative metabolites using on-line solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. We used proportional probabilities models to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusting for potential confounders. Results: Concentrations of some non-persistent EDCs were associated with reduced fecundability. The adjusted FR for the highest vs. lowest quartile of benzophenone-3 was 0.53 (95% CI: 0.28-0.99), with evidence of a monotonic association. Bisphenol S and 2,5’-dichlorophenol, and ethyl paraben concentrations were also associated with reduced fecundability. Among phthalate metabolites, mono-ethyl phthalate (highest vs. lowest quartile: FR=0.71, 95% CI: 0.45-1.12), monocarboxyoctyl phthalate (highest vs. lowest quartile: FR=0.71, 95% CI: 0.44-1.14), and the non-phthalate plasticizer cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (≥0.6 µg/g creatinine vs. <limit of detection: FR=0.59, 95% CI: 0.37-0.95) were associated with reduced fecundability. Conclusions: Biomarkers of some non-persistent EDCs were associated with reduced fecundability. Future analysis of additional urine specimens in these cohorts will enable examination of chemical mixtures on fecundability. Key words: endocrine-disrupting chemicals, fecundability, fertility, phenols, phthalates