PFAS in Follicular Fluid, Anti-Mullerian Hormone, and Oocyte Developmental Competence: A Prospective Study in GIVES

Abstract In this prospective study based on the Guangxi In Vitro Fertilization and the Environment Study (GIVES) cohort, we measured poly- and perfluoroalkyl substances (PFAS) in the ovarian follicular fluid of 729 participants to investigate their association with oocyte developmental competence. The PFAS mixture was negatively associated with Metaphase II (MII) oocyte rate, with chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) identified as the primary contributor in Bayesian kernel machine regression (BKMR) models. Cl-PFESAs were negatively associated with oocyte maturation [relative risk (RR) = 0.67, 95% CI: 0.56–0.79], fertilization (RR = 0.78, 95% CI: 0.67–0.90), blastocyst formation (RR = 0.81, 95% CI: 0.70–0.94), and high-quality blastocyst formation (RR = 0.49, 95% CI: 0.41–0.58). Serum anti-Müllerian hormone (AMH) may act as a key modifier, with a stronger association observed in women with low AMH for MII oocyte rate [relative excess risk due to interaction (RERI) = 0.33, 95% CI: 0.12–0.54] and fertilization rate (RERI = 0.24, 95% CI: 0.003–0.49). Our findings indicate that PFAS, particularly Cl-PFESAs, in follicular fluid are linked to impaired oocyte developmental competence, with AMH serving as a potential modifier. Further studies are warranted to validate our findings and assess the implications of PFAS for reproductive outcomes.