Exposure profiles of legacy and emerging per- and polyfluoroalkyl substances in follicular fluid and their impacts on assisted reproductive outcomes: A multicenter study in China

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with potential reproductive toxicity, yet their profiles in follicular fluid and impacts on human fertility remain unclear. Given the importance of diet as an exposure pathway, we aimed to characterize PFAS in follicular fluid, examine associations with reproductive outcomes, and explore dietary contributors across regions in China. In this multicenter study involving 1301 women undergoing assisted reproductive technology in eight administrative divisions, 20 PFAS were quantified in follicular fluid. Reproductive outcomes included live birth, pregnancy loss, and early measures of ovarian hormones, endometrial thickness, and oocyte or embryo development. Associations were estimated using center-specific regression models combined by meta-analysis, with false discovery rate (FDR) correction. Both legacy and emerging PFAS were detected, with perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid contributing 19%–40% and 23%–37% of total concentrations, respectively, and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) 11%–19%. Concentrations were higher in eastern and southern centers. Higher PFOS concentrations were significantly associated with an increased risk of biochemical pregnancy loss after FDR correction (RR per natural-log-unit increase: 2.10; 95% CI: 1.28, 3.45). Several legacy PFAS were linked to lower luteinizing hormone, elevated progesterone, and thinner endometrium on the day of human chorionic gonadotropin. Comparable associations were observed for emerging PFAS. Dietary intake of aquatic food and other animal-derived foods correlated positively with PFAS concentrations. These findings highlight PFAS accumulation in the ovarian microenvironment and potential disruption of early reproductive processes, underscoring the need for exposure mitigation through modifiable dietary pathways.