Urinary concentrations of bisphenol A, parabens and phthalate metabolite mixtures in relation to reproductive success among women undergoing in vitro fertilization.
Level 3 - non-randomized controlled study
Prospective observational cohort study evaluating biomarker exposures and clinical IVF outcomes.
PubMed 30826614 · doi:10.1016/j.envint.2019.02.025
What was done
This prospective cohort study evaluated 420 women undergoing 648 in vitro fertilization (IVF) cycles (1,145 urine samples collected prior to oocyte retrieval) between 2006 and 2017 at the Massachusetts General Hospital Fertility Center. Urinary concentrations of bisphenol A (BPA), parabens, and phthalate metabolites were measured using isotope-dilution tandem mass spectrometry. Chemical mixture patterns were analyzed using principal component analysis (PCA) and Bayesian kernel machine regression (BKMR). Associations between exposure quartiles and IVF outcomes were assessed via generalized linear mixed models, with sensitivity analyses restricted to 2006–2012 cycles due to temporal exposure declines.
What was found
Urinary concentrations of BPA, parabens, and most phthalates were significantly lower during 2013–2017 compared to 2006–2012. In the full cohort, neither PCA factors (DEHP, non-DEHP, paraben) nor BKMR mixture analyses demonstrated associations with IVF outcomes. In sensitivity analyses restricted to the higher-exposure 2006–2012 period, women in the highest versus lowest quartile of the DEHP factor experienced lower probabilities of implantation (-22%, p-trend = 0.08), clinical pregnancy (-24%, p-trend = 0.14), and live birth (-38%, p-trend = 0.06). BKMR did not isolate a single chemical driving these associations.
Why it matters
This study assesses real-world concurrent mixtures of common endocrine-disrupting chemicals rather than single agents, finding null associations overall amid declining contemporary population exposures.
Limits
Single-center population undergoing assisted reproduction limits generalizability to spontaneous conception. Substantial temporal decreases in chemical levels complicate pooled analysis across the 11-year window, and subgroup associations in earlier years did not reach conventional statistical significance.
Cited by
- partial The EARTH study demonstrated that higher exposure to endocrine-disrupting chemicals is associated with increased time to pregnancy and worse IVF outcomes, including fewer retrieved eggs, fewer embryos, and poorer sperm counts.