{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:06:02Z","timestamp":1784696762548,"version":"3.55.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To study whether the duration of estradiol exposure in hormone replacement therapy (HRT) cycles for frozen embryo transfer (FET) is associated with progesterone-related cycle cancellation and reproductive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included 2, 001 HRT\u2013FET cycles following a freeze-all strategy performed between January 2020 and June 2025. Patients were stratified according to estradiol exposure duration into short (8\u20139 days; n = 980), intermediate (10\u201311 days; n = 746), and prolonged (12\u201314 days; n = 275) exposure groups. Serum progesterone levels were assessed on the day of progesterone initiation. The primary outcome was cycle cancellation due to progesterone elevation (progesterone \u22651.5 ng\/mL on the day of progesterone initiation). Secondary outcomes included implantation, clinical pregnancy, miscarriage, and live birth rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall cycle cancellation rate was 3.3% (66\/2, 001) and increased significantly with longer estradiol exposure, occurring in 2.1%, 3.9%, and 5.8% of cycles in the short, intermediate, and prolonged groups, respectively (OR 1.69 per category, 95% CI 1.22-2.34, p = 0.002). Live birth rates per transfer were similar across groups (47.2%, 52.3%, and 49.4%, respectively; p = 0.122). In multivariable analysis, prolonged estradiol exposure (OR 3.68, 95% CI 1.76\u20137.71, p &amp;lt; 0.001), intermediate exposure (OR 2.08, 95% CI 1.13\u20133.81, p = 0.019), age &amp;gt;37 years (OR 2.58, 95% CI 1.36\u20134.90, p = 0.004), and diminished ovarian reserve (OR 5.13, 95% CI 2.87\u20139.16, p &amp;lt; 0.001) were independent predictors of cycle cancellation, whereas polycystic ovary syndrome (OR 0.23, 95% CI 0.08\u20130.69, p = 0.009) was independently associated with a lower likelihood of cancellation. In the multivariable model restricted to transferred cycles, neither intermediate nor prolonged estradiol exposure was independently associated with live birth compared with short estradiol exposure (intermediate: OR 1.25, 95% CI 0.88\u20131.78, p = 0.204; prolonged: OR 0.93, 95% CI 0.57\u20131.51, p = 0.775).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prolonged estradiol exposure in HRT\u2013FET cycles is associated with increased progesterone-related cycle cancellation without improving reproductive outcomes. A patient-tailored approach based on ovarian reserve status and age may help reduce avoidable cancellations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1898027","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:40:11Z","timestamp":1784695211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing estradiol duration to reduce progesterone-related cancellation in hormone replacement therapy frozen embryo transfer cycles: toward a patient-tailored approach"],"prefix":"10.3389","volume":"17","author":[{"given":"Mehmet Resit","family":"Asoglu","sequence":"first","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, T\u00fcrkiye"]},{"name":"Department of Obstetrics and Gynecology, Uskudar University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi","family":"Dar\u0131c\u0131 Kurt","sequence":"additional","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurkan","family":"Bozdag","sequence":"additional","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kubra","family":"Boynukalin","sequence":"additional","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozkan","family":"Ozdamar","sequence":"additional","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Bahceci","sequence":"additional","affiliation":[{"name":"Bahceci IVF center","place":["Istanbul, 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