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 E₂, P, total T, and antimüllerian 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 E₂, P, and T levels. Women in the third tertile of MMP had decreases of 34.23%, 9.44 ng/L, and 23.28% in E₂, 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.