Differential associations of PFAS in follicular fluid and serum with reproductive hormones: Insights from a Chinese IVF cohort GIVES.

Per- and polyfluroroalkyl substances (PFAS) are potential endocrine disruptors, but their associations with reproductive hormones remain inconsistent, and evidence linking PFAS in ovarian follicular fluid (FF) to hormones is limited. In this study, we investigated these associations among 501 women undergoing in vitro fertilization (IVF) treatment from the GIVES cohort, with PFAS levels measured in follicular fluid from all participants and in serum from a subset of 410 women. Serum samples were collected on menstrual cycle days 2-5 and the ovulation trigger day for hormone measurement, and PFAS levels were assessed in FF and serum. We found distinct associations between PFAS in FF and serum with reproductive hormones. For example, the highest quartile of FF 6:2 Cl-PFESA was negatively associated with basal luteinizing hormone (LH) (β = -0.13, 95 %CI: 0.23, -0.02), while that of serum 6:2 Cl-PFESA was positively associated with basal LH (β = 0.13, 95 %CI: 0.01, 0.25), compared to the lowest quartile. Additionally, significant associations were identified between certain PFAS and hormones following controlled ovarian stimulation. Bayesian Kernel Machine Regression models indicated a negative association between a mixture of nine FF PFAS and basal follicle stimulating hormone. These findings provide new insights into PFAS exposure and female reproductive hormones, highlighting the importance of measuring PFAS in multiple biological matrices to comprehensively assess their effects on ovarian health.