Follicular fluid concentrations of phthalate metabolites are associated with altered intrafollicular reproductive hormones in women undergoing in vitro fertilization

Objective To explore whether follicular fluid (FF) concentrations of phthalate metabolites are associated with levels of intrafollicular reproductive hormones in women undergoing in vitro fertilization. Design Cross-sectional study. Setting University-affiliated reproductive medicine center. Patient(s) A total of 194 women each contributed one FF sample at oocyte retrieval. Intervention(s) FF aspirates from individual follicles (≥18 mm in diameter) were collected. We measured eight phthalate metabolites and four ovarian hormones in the FF samples. Main Outcome Measure(s) Per-follicle E 2 , P, total T, and antimullerian hormone (AMH) concentrations. Result(s) Most phthalate metabolites were highly detected in FF samples. We observed a dose-response relationship between increasing monomethyl phthalate (MMP) tertiles and lower E 2 , P, and T levels. Women in the third tertile of MMP had decreases of 34.23%, 9.44 ng/L, and 23.28% in E 2 , P, and T, respectively, compared with women in the first tertile. Tertiles of monoethyl phthalate and the percentage of di(2-ethylhexyl) phthalate) metabolites excreted as mono(2-ethylhexyl) phthalate were inversely associated with P. We also identified a negative relationship between monobenzyl phthalate tertiles and AMH. In addition, positive correlations between some of the phthalate metabolites and ovarian hormones were detected. Conclusion(s) FF concentrations of certain phthalate metabolites were associated with altered levels of intrafollicular reproductive hormones, which raises concern over a potential deleterious effect of environmental phthalate exposure on the endocrine capacity and viability of theca and granulosa cells.