{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:56:04Z","timestamp":1775753764390,"version":"3.50.1"},"reference-count":33,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gynecol Obstet Invest"],"abstract":"<jats:p>&lt;p&gt;Objectives: Alterations in 17\u03b2-estradiol metabolism are known to potentially impair endometrial receptivity. Previous pioneering studies have investigated the role of endometrial steroid metabolism by determining steroid hormone levels and steroid-metabolizing enzyme activity in endometrial biopsies of patients undergoing IVF. The activity of oxidative and reductive 17\u03b2-hydroxysteroid dehydrogenases (17\u03b2-HSDs), which catalyze the interconversion between estrone and 17\u03b2-estradiol, was found to be similar between IVF patients who \u2013 after fresh embryo transfer in the cycle following endometrial biopsy \u2013 did and did not become pregnant. However, inhibition of the reductive enzyme 17\u03b2-hydroxysteroid dehydrogenase type 1 (17\u03b2-HSD1), the most prominent 17\u03b2-HSD type in 17\u03b2-estradiol formation, was found to differ between groups. The primary objective of this study was to determine oxidative and reductive 17\u03b2-HSD enzyme activity in the endometrium of two well-defined groups: IVF patients with recurrent implantation failure (RIF) and control patients. Design: This is a prospective observational study of IVF patients with RIF (n = 52) and controls (n = 25). Patients undergoing treatment because of pre-implantation genetic testing, a severe male factor, or bilateral tubal pathology were recruited as controls since these conditions did not suggest an endometrial contribution to infertility. Participants\/Materials, Setting, Methods: Endometrial biopsies were obtained 5\u20138 days after a positive urine ovulation test in a natural cycle using a Pipelle catheter. Activity of oxidative and reductive enzymes, inhibition of 17\u03b2-HSD1, 5, 7, and 12, and immunostaining of 17\u03b2-HSD7 were performed. The formation of 17\u03b2-estradiol by reduction of estrone (reductive enzymes), formation of estrone by oxidation of 17\u03b2-estradiol (oxidative enzymes), and inhibition of specific 17\u03b2-HSD enzymes were determined using high-performance liquid chromatography. Formalin-fixed paraffin-embedded tissue was used for immunostaining. The Student\u2019s t test and Mann-Whitney U test were used for statistical analysis. Multivariate analysis was used to determine the influence of confounders. Results: No differences were found in activity of oxidative and reductive 17\u03b2-HSD enzymes in RIF patients and controls. Combined inhibition of 17\u03b2-HSD5, 7, and 12 was significantly lower in the RIF group compared to controls (p = 0.04). Inhibition of 17\u03b2-HSD1 and 17\u03b2-HSD7 combined was also significantly lower (more production of 17\u03b2-estradiol remained) in the RIF group compared to controls (p &lt; 0.01). However, solely inhibiting 17\u03b2-HSD1 or 17\u03b2-HSD7 showed no significant difference between groups. Immunostaining revealed the expression of 17\u03b2-HSD7 in all endometrial samples. Limitations: Results should be interpreted carefully due to possible cycle-to-cycle variation, challenges to translate in vitro findings to biological conditions, and the heterogeneous etiology of RIF. Conclusions: Differences in formation of 17\u03b2-estradiol in the presence of two specific inhibitors of 17\u03b2-HSD1 and 7 between RIF patients and controls were found. Although 17\u03b2-HSD1, expressed at the fetal-maternal interface, has been associated with fertility, the potential role of 17\u03b2-HSD7 in human implantation has not been previously described. The observed differences between patients with RIF and controls warrant future research on the role of this main enzyme and its lesser-known 17\u03b2-HSD type in endometrial receptivity and implantation. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000546442","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T12:01:50Z","timestamp":1747396910000},"page":"151-162","source":"Crossref","is-referenced-by-count":1,"title":["Endometrial Metabolism of 17\u03b2-Estradiol during the Window of Implantation in Women with Recurrent Implantation Failure"],"prefix":"10.1159","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7650-8837","authenticated-orcid":false,"given":"Linda B.P.M","family":"Stevens Brentjens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Delvoux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janneke E.","family":"den Hartog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darina","family":"Obukhova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Xanthoulea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron J.T.","family":"van 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