Poor endometrial proliferation after clomiphene is associated with altered estrogen action

Context: Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene.

Objective: To examine cellular and molecular differences in the endometrium of women with suboptimal versus optimal endometrial thickening following clomiphene.

Design: Translational prospective cohort study from 2018-2020.

Setting: University-affiliated clinic.

Patients or Participants: Reproductive age women with unexplained infertility treated with 100mg of clomiphene cycle days 3-7 who developed optimal (≥8mm; n=6, controls) or suboptimal (<6mm; n=7, subjects) endometrial thickness.

Interventions: Pre-ovulatory blood and endometrial sampling.

Main outcome measures: Endometrial tissue architecture, abundance and location of specific proteins, RNA expression, ERa binding.

Results: The endometrium of suboptimal subjects compared to optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%...