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

Follicular fluid phthalate metabolites were associated with differing concentrations of intrafollicular reproductive hormones, suggesting a possible role of environmental phthalate exposure in altering the endocrine capacity and viability of follicular cells.

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Volume 111, Issue 5, Pages 953–961


Yaoyao Du, M.M.a, Na Guo, M.M.a, Yixin Wang, Ph.D.b,c,d, Xuemei Teng, B.M.a, Xiang Hua, M.D.a, Taoran Deng, M.D.a, Yangcheng Yao, B.M.a, Xiaoqiong Yuan, B.M.a, Yufeng Li, M.D.



To explore whether follicular fluid (FF) concentrations of phthalate metabolites are associated with levels of intrafollicular reproductive hormones in women undergoing in vitro fertilization.


Cross-sectional study.


University-affiliated reproductive medicine center.


A total of 194 women each contributed one FF sample at oocyte retrieval.


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.


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.


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.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.