Lower conception rates are related with suboptimal endometrial thickness, which happens in certain infertile women treated with clomiphene. The purpose of this study was to look at cellular and molecular variations in the endometrium of women who had poor vs. optimum endometrial thickening after taking clomiphene. From 2018 through 2020, a translational prospective cohort research will be conducted in a university-affiliated clinic. Preovulatory blood and endometrial sampling was performed on reproductive-age women with unexplained infertility who were treated with 100 mg of clomiphene on cycle days 3 to 7 and who developed optimal or suboptimal endometrial thickness. Endometrial tissue architecture, the quantity and location of particular proteins, RNA expression, and oestrogen receptor (ER) binding were the primary outcome measures. When compared to optimum controls, the endometrium of subpar patients had a lower amount of glandular epithelium, lower immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), higher immunostaining of pan-leukocyte marker CD45 and ER, but lower ER immunostaining. RNA-seq revealed 398 genes that differed across groups. In subpar individuals, pathway analysis of differentially expressed genes revealed decreased proliferation, decreased angiogenesis, elevated inflammation, and ER activation. ChIP-seq revealed six ER-bound genes that were differentially expressed between groups, some of which may be involved in implantation.
Women who have inadequate endometrial thickness following clomiphene have abnormal ER expression patterns, architectural alterations, and changed gene and protein expression, implying decreased proliferation and angiogenesis in the context of elevated inflammation.