The effect of endocrine-disrupting chemicals in follicular fluid: The insights from oocyte to fertilization

Endocrine-disrupting chemicals (EDCs) exhibited the detriment in female reproductive health. Our objective was to investigate the individual and mixture effects of EDCs present in follicular fluid, the environment in which oocytes grow and develop, on early reproductive outcomes. We recruited 188 women seeking reproduction examination from the Study of Exposure and Reproductive Health (SEARCH) cohort between December 2020 and November 2021. We assessed the concentrations of 7 categories of 64 EDCs in follicular fluid, and measured early reproductive outcomes, including retrieved oocytes, mature oocytes, normal fertilized oocytes, and highquality embryos. In this study Monomethyl phthalate (MMP) (2.17 ng/ml) were the compounds found in the highest median concentrations in follicular fluid. After adjusting for multiple testing, multivariate regression showed that multiple EDCs were significantly negatively associated with early assisted reproduction outcomes. For example, MMP showed a significant negative correlation with the number of high quality embryos (beta: -0.1, 95% CI: -0.15, -0.04). Specifically, eight types of EDCs were significantly negatively associated with four early assisted reproductive outcomes (beta range: -0.2 similar to -0.03). In the mixed exposure model, we found that mixtures of EDC were significantly negatively correlated with all four outcomes. In the quantile g-computation (QGCOMP) model, for each interquartile range increase in the concentration of EDC mixtures, the number of oocytes retrieved, mature oocytes, normally fertilized oocytes, and high-quality embryos decreased by 0.46, 0.52, 0.77, and 1.2, respectively. Moreover, we identified that phthalates (PAEs) predominantly contributed to the negative effects. Future research should validate our findings.