ArticleThe Journal of clinical endocrinology and metabolism2021
Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.
Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Therapeutic mechanisms of Zi Chong granules against hydroxyurea-induced diminished ovarian reserve based on integrated multi-omics analyses.Journal of ovarian research · 2025Article
- Clomiphene Citrate Administered in Periconception Phase Causes Fetal Loss and Developmental Impairment in Mice.Endocrinology · 2024Article
- A critical appraisal of studies on endometrial thickness and embryo transfer outcome.Reproductive biomedicine online · 2023Review
- Estradiol regulates oxidative stress and angiogenesis of myocardial microvascular endothelial cells via the CDK1/CDK2 pathway.Heliyon · 2023Article
- The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids.Endocrinology · 2022Article
- Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell-Cell Communication Network Using CellChat.Frontiers in cell and developmental biology · 2022Article
- What Is the Mechanism of Poor Endometrial Proliferation in Patients With Unexplained Infertility After Clomiphene Citrate Treatment?The Journal of clinical endocrinology and metabolism · 2021Article
- Poor Endometrial Proliferation After Clomiphene is Associated With Altered Estrogen Action.The Journal of clinical endocrinology and metabolism · 2021Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
contextSuboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene.
objectiveTo examine cellular and molecular differences in the endometrium of women with suboptimal vs optimal endometrial thickening following clomiphene.
methodsTranslational prospective cohort study from 2018 to 2020 at a university-affiliated clinic. Reproductive age women with unexplained infertility treated with 100 mg of clomiphene on cycle days 3 to 7 who developed optimal (≥8mm; n = 6, controls) or suboptimal (<6mm; n = 7, subjects) endometrial thickness underwent preovulatory blood and endometrial sampling. The main outcome measures were endometrial tissue architecture, abundance and location of specific proteins, RNA expression, and estrogen receptor (ER) α binding.
resultsThe endometrium of suboptimal subjects compared with optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%, P = .01), decreased immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), increased immunostaining of pan-leukocyte marker CD45 and ERβ, but decreased ERα immunostaining (all P < .05). RNA-seq identified 398 differentially expressed genes between groups. Pathway analysis of differentially expressed genes indicated reduced proliferation (Z-score = -2.2, P < .01), decreased angiogenesis (Z-score = -2.87, P < .001), increased inflammation (Z-score = +2.2, P < .01), and ERβ activation (Z-score = +1.6, P < .001) in suboptimal subjects. ChIP-seq identified 6 genes bound by ERα that were differentially expressed between groups (P < .01), some of which may play a role in implantation.
conclusionWomen with suboptimal endometrial thickness after clomiphene exhibit aberrant ER expression patterns, architectural changes, and altered gene and protein expression suggesting reduced proliferation and angiogenesis in the setting of increased inflammation.
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