{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:00:28Z","timestamp":1791669628756,"version":"4.3.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Clinically, it has been observed that vaginal administration of the same dose of Micronized 17-beta estradiol hemihydrate (the Estradiol tablets of Femoston) significantly increases serum estradiol levels compared to oral administration. However, the clinical outcomes associated with this route of administration remain unclear. Additionally, the concentration of estradiol in endometrial tissue following vaginal administration of Micronized 17-beta estradiol hemihydrate (M17EH), as well as its potential impact on endometrial receptivity, has been poorly investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore the relationship between different drug regimens of M17EH hormone replacement (HRT) and serum estradiol level, endometrial thickness and embryo implantation outcome in patients with thin endometrium during the frozen-thawed embryo transfer (FET) cycle, and to analyze the estradiol concentration in endometrial tissue of oral and vaginal administration of M17EH and its influence on endometrial receptivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A retrospective analysis was conducted on patients with thin endometrium. Subjects were divided into three groups based on different estrogen formulations and administration routes: Group A [oral Estradiol Valerate Tablets (Progynova)], Group B (oral M17EH), and Group C (oral combined with vaginal M17EH). Endometrial thickness, and clinical outcomes were compared across the three groups. For Groups B and C, endometrial tissue samples were collected five days after progesterone conversion. Estradiol concentration in tissues was detected and the endometrial receptivity markers [leukemia inhibitory factor, (LIF) and Mucins, (Muc1)] were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum estradiol levels and endometrial thickness in Group C were significantly higher than those in the other two groups (P &amp;lt; 0.05). While there were no statistically significant differences in abortion rate, and live birth rate among the three groups, the live birth rate was highest in Group C. Estradiol concentration in the endometrium was significantly higher following vaginal administration of M17EH compared to oral administration (P&amp;lt;0.05). No significant differences were observed in the expression of endometrial receptivity markers (LIF and MUC1) between oral and vaginal administration groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In FET cycles, a HRT regimen combining oral and vaginal administration of Micronized 17-beta estradiol hemihydrate is more conducive to endometrial growth. Although vaginal administration results in higher estrogen levels, it does not appear to compromise endometrial receptivity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1639481","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T04:12:49Z","timestamp":1758255169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical outcomes of different 17\u03b2-estradiol drug regimens and their impact on endometrial receptivity"],"prefix":"10.3389","volume":"16","author":[{"given":"Beining","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinXiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingsheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinxiu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4274\/tjod.47855","article-title":"Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A randomized prospective trial","volume":"15","author":"Agha-Hosseini","year":"2018","journal-title":"Turk J Obstet Gynecol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-021-06371-6","article-title":"Endometrial preparation methods prior to frozen embryo transfer: A retrospective cohort study comparing true natural cycle, modified natural cycle and artificial cycle","volume":"306","author":"Mensing","year":"2022","journal-title":"Arch Gynecol Obstet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.rbmo.2019.02.013","article-title":"Management of thin endometrium in assisted reproduction: a clinical practice guideline from the Canadian Fertility and Andrology Society","volume":"39","author":"Liu","year":"2019","journal-title":"Reprod BioMed Online"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4103\/jhrs.JHRS_60_20","article-title":"Effect of endometrial thickness and duration of estrogen supplementation on in vitro fertilization-intracytoplasmic sperm injection outcomes in fresh ovum\/embryo donation cycles","volume":"14","author":"Patel","year":"2021","journal-title":"J Hum Reprod Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.23750\/abm.v94i3.14437","article-title":"Endometrial thickness and live birth rates after IVF: a systematic review","volume":"94","author":"Moshkalova","year":"2023","journal-title":"Acta Biomed"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0376-2491.2013.47.012","article-title":"Application of Femoston in hormone replacement treatment-frozen embryo transfer and its clinical outcomes","volume":"93","author":"Xu","year":"2013","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der037","article-title":"The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting","volume":"26","author":"Balaban","year":"2011","journal-title":"Hum Reprod"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9378(99)70042-6","article-title":"Serum and tissue hormone levels of vaginally and orally administered estradiol","volume":"180","author":"Tourgeman","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/biom15010106","article-title":"Endometrial receptivity-lessons from \"Omics","volume":"15","author":"Ye","year":"2025","journal-title":"Biomolecules"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1268990","article-title":"Impaired receptivity of thin endometrium: therapeutic potential of mesenchymal stem cells","volume":"14","author":"Saad-Naguib","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1186\/s12884-022-04903-9","article-title":"Obstetric outcomes following ovarian hyperstimulation syndrome in IVF - a comparison with uncomplicated fresh and frozen transfer cycles","volume":"22","author":"Ganer Herman","year":"2022","journal-title":"BMC Pregnancy Childbirth"},{"key":"B12","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s10815-013-0117-8","article-title":"The impact of supraphysiologic serum estradiol levels on peri-implantation embryo development and early pregnancy outcome following in vitro fertilization cycles","volume":"31","author":"Imudia","year":"2014","journal-title":"J Assist Reprod Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1372753","article-title":"High progesterone levels on the day after HCG injection has no effect on clinical pregnancy outcomes in in vitro fertilization-embryo transfer","volume":"15","author":"Liang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12958-024-01260-4","article-title":"Impact of elevated serum estradiol levels before progesterone administration on pregnancy outcomes in frozen-thawed embryo transfer for hormone replacement therapy","volume":"22","author":"Shuai","year":"2024","journal-title":"Reprod Biol Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2024.2352142","article-title":"Effect of estrogen exposure on pregnancy outcomes in artificial frozen-thawed embryo transfer cycles","volume":"40","author":"Wei","year":"2024","journal-title":"Gynecol Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s12884-022-04605-2","article-title":"The relationship between serum estrogen levels and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study","volume":"22","author":"Kong","year":"2022","journal-title":"BMC Pregnancy Childbirth"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1673-4254.2018.05.16","article-title":"Effect of serum estradiol level before progesterone administration on pregnancy outcomes of frozen-thawed embryo transfer cycles","volume":"38","author":"Deng","year":"2018","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-021-00549-8","article-title":"Elevated serum estradiol levels do not inhibit implantation during frozen embryo transfer cycles","volume":"28","author":"Choi","year":"2021","journal-title":"Reprod Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1038\/s41598-023-27877-w","article-title":"Effects of serum estrogen levels before frozen-thawed blastocyst transfer on pregnancy outcomes in hormone replacement cycles","volume":"13","author":"Du","year":"2023","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(00)01640-x","article-title":"Endocrine and clinical effects of hemihydrate estradiol administered vaginally or orally","volume":"75","author":"Tourgeman","year":"2001","journal-title":"Fertil Steril"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1639481\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:57:56Z","timestamp":1759413476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1639481\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":20,"alternative-id":["10.3389\/fendo.2025.1639481"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1639481","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]},"article-number":"1639481"}}