Poor Endometrial Proliferation after Clomiphene is Associate
Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene.

This study aimed to examine cellular and molecular differences in the endometrium of women with suboptimal versus optimal endometrial thickening following clomiphene.

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 were examined.

-- The endometrium of suboptimal subjects compared to optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%), decreased immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), increased immunostaining of pan-leukocyte marker CD45 and ER?, but decreased ER?immunostaining.

-- RNAS-seq identified 398 differentially expressed genes between groups. Pathway analysis of differentially expressed genes indicated reduced proliferation, decreased angiogenesis, increased inflammation, and ER?activation in suboptimal subjects. ChIP-seq identified 6 genes bound by ER? that were differentially expressed between groups (P<0.01), some of which may play a role in implantation.

Conclusively, women with suboptimal endometrial thickness after clomiphene exhibit aberrant estrogen receptor expression patterns, architectural changes and altered gene and protein expression suggesting reduced proliferation and angiogenesis in the setting of increased inflammation.

Source: https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab381/6290161?redirectedFrom=fulltext