Serum PFAS mixtures and risk of ovarian hyperstimulation syndrome in women undergoing assisted reproduction.

BACKGROUND

Per- and polyfluoroalkyl substances (PFAS) are persistent endocrine disruptors affecting ovarian steroidogenesis. However,their impact onovarian hyperstimulation syndrome (OHSS), a potentially life-threatening iatrogenic complication of assisted reproductive technology (ART),remains unknown.

METHODS

We prospectively enrolled 374 women undergoing their first ART cycle in China (2021-2023), of whom 103 developed OHSS. We quantified 43 serum PFAS using UPLC-MS/MS,retaining 12 congeners with detection frequencies > 50%for subsequent analyses, and four congeners with detection frequencies > 70% were included in mixture analyses. Associations were evaluated using modified Poisson regression, restricted cubic splines, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp).

RESULTS

In continuous variable models, log10-transformed concentrations of PFNA, PFDA, and PFUdA were significantly associated with an elevated risk of OHSS (adjusted RR [aRR] = 1.30, 95% CI: 1.08-1.58, p = 0.006; aRR = 1.21, 95% CI: 1.01-1.44, p = 0.034; and aRR = 1.42, 95% CI: 1.16-1.73, p < 0.001, respectively). Tertile analyses further confirmed these dose-dependent positive associations. Mixture analyses via BKMR identified PFNA and OBS as dominant risk contributors, with a non-monotonic overall mixture-response relationship. These adverse associations were primarily concentrated in women < 35 years.

CONCLUSIONS

To our knowledge, this study provides the first epidemiological evidence linking specific PFAS congeners and their mixtures to elevated OHSS risk during ART, supporting the rationale for preconception PFAS biomonitoring and targeted exposure reduction in reproductive-age women.