First evidence of legacy and emerging per- and polyfluoroalkyl substances (PFAS) in the follicular fluid of a cohort of North Carolina in vitro fertilization (IVF) patients.

Despite widespread per- and polyfluoroalkyl substances (PFAS) contamination in North Carolina (NC), such as in the Cape Fear region, and documented detection in drinking water and serum, little is known about their accumulation in human follicular fluid (FF)-a critical microenvironment for oocyte maturation. Therefore, the aim of this study was to quantify PFAS in the FF of 86 women undergoing in vitro fertilization (IVF) in NC. Using targeted analysis, we measured 23 PFAS including legacy, alternatives, and emerging ether compounds. PFAS were detected in all samples, with the highest levels in perfluoroalkyl sulfonic acids (PFSAs) such as PFHxS and PFOS (2.36 and 1.28 ng/mL). Detection frequencies varied by chemical class, with legacy perfluoroalkyl carboxylic acids (PFCAs) and PFSAs detected more often than emerging alternatives. Interestingly, hexafluoropropylene oxide dimer acid (GenX) was detected in 88 % of samples and this PFAS is not frequently detected in human serum. Three to 16 analytes were detected per patient in a range of 0.5-12.8 ng/mL. The cumulative PFAS load was not significantly different between patients with and without an infertility diagnosis, though individual variability was high. This is the first study to examine PFAS in FF in NC and confirms that both legacy and alternative PFAS can cross the blood-follicle barrier to accumulate in FF. This study detected several compounds at a high frequency that have not been previously reported in NC serum, including PFDS, PFTrA, and GenX.