High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients

Sci Rep. 2024 Oct 4;14(1):23100. doi: 10.1038/s41598-024-74295-7.

Abstract

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Keywords: Androgen; Embryo transfer; Endometrial receptivity; PCOS.

MeSH terms

  • Adult
  • Androgens / blood
  • Androgens / metabolism
  • Embryo Implantation
  • Embryo Transfer*
  • Endometrium* / metabolism
  • Female
  • Fertilization in Vitro / methods
  • Humans
  • Infertility, Female / blood
  • Infertility, Female / metabolism
  • Infertility, Female / therapy
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Leukemia Inhibitory Factor* / metabolism
  • Ovulation Induction* / methods
  • Polycystic Ovary Syndrome* / metabolism
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Rate
  • Retrospective Studies
  • Testosterone* / blood

Substances

  • Leukemia Inhibitory Factor
  • Testosterone
  • Insulin-Like Growth Factor Binding Protein 1
  • Androgens
  • LIF protein, human
  • IGFBP1 protein, human