Exposure to endocrine-disrupting chemicals in follicular fluid: implications for assisted reproductive technology...

Are endocrine-disrupting chemicals (EDC) in follicular fluid associated with assisted reproductive technology (ART) outcomes among women undergoing ART treatment?

This prospective cohort study involved 176 women who underwent ART treatment in China. The concentrations of 76 EDC, across five categories, in follicular fluid were quantified. Generalized linear models (with and without restricted cubic splines to account for non-linear relationships) and Bayesian kernel machine regression (BKMR) models were utilized.

Fifteen EDC exhibited significant negative associations with at least one conventional IVF/intracytoplasmic sperm injection (ICSI) outcome. Notably, mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) was consistently associated with reductions in all conventional IVF/ICSI outcomes, including the numbers of retrieved oocytes, mature oocytes, two pronuclear zygotes, blastocysts and high-quality embryos. Similarly, 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) was negatively associated with all conventional IVF/ICSI outcomes except the number of blastocysts. No significant negative associations were observed between individual EDC and pregnancy outcomes, including the live birth rate. BKMR model analyses revealed that combinations of EDC were significantly associated with reductions in the numbers of retrieved oocytes and mature oocytes, and the probability of biochemical pregnancy. Among EDC combinations, phthalates (PAE) and bisphenol S (BPS) were identified as dominant contributors to adverse conventional IVF/ICSI outcomes and the biochemical pregnancy rate, respectively. Stratified and interaction analyses further indicated that stronger associations with conventional IVF/ICSI outcomes were observed among women aged ≤33 years.

Elevated concentrations of EDC in follicular fluid were associated with adverse ART outcomes, both as individual compounds and in combination. MECPP, BHT-COOH, PAE and BPS were identified as key EDC. Moreover, the associations were modified by age, with stronger adverse effects observed in younger women.