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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

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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.

Impact/Purpose

The findings in this study are unique as they demonstrate that both legacy and emerging PFAS are detectable in the follicular fluid of NC residing women, with sulfonates such as PFHxS and PFOS present at the highest concentrations and emerging PFAS such as GenX and PFHpS also detected in high frequencies.  Since GenX is not detected in serum samples, the detection of this PFAS in follicular fluid along with a few others not typically found in follicular fluid are novel.  Given this observed shift in the detection of more emerging chemicals with less information on potential health effects, especially of mixtures, there is a growing need to investigate the impact of alternative PFAS on endocrine disruption, oocyte maturation and female fertility. Future research should prioritize the identification of susceptible windows of exposure and delineate the mechanisms of ovarian toxicity, while also considering effects of mixtures as characterized in the present study.   A full impact statement for advance notification is attached below.       

Citation

Shuping Boney, S., C. Christen, B. Wetmore, A. Murr, D. Raburn, S. Young, C. Abraham, AND T. Stoker. 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. Elsevier Science Ltd, New York, NY, 139:109102, (2026). [DOI: 10.1016/j.reprotox.2025.109102]

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DOI: 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
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Last updated on June 26, 2026
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