{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T05:15:04Z","timestamp":1769318104352,"version":"3.49.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Do serum estradiol (E2) levels on the day of frozen blastocyst transfer (FBT) affect pregnancy outcomes in hormonal replacement therapy (HRT) cycles using transdermal estrogens?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>E2 levels \u2265313\u2009pg\/ml on the day of FBT are associated with increased early miscarriage rates (EMRs), but do not significantly impact the live birth rate (LBR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>E2 plays a crucial role in endometrial receptivity and placentation. The effect of serum E2 levels measured around the time of FBT in HRT cycles remains debated, with some studies indicating a negative impact of high E2 levels and others finding no significant difference. Currently, no studies focus exclusively on HRT cycles using transdermal estrogens, which are considered safer regarding thromboembolic complications.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This retrospective cohort study analyzed 2364 patients undergoing HRT-FBT cycles at a university hospital between January 2019 and December 2022. Each patient was included only once during the study period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>The study involved patients undergoing single autologous FBT under HRT with transdermal estrogens and vaginal micronized progesterone. Serum E2 levels were measured in the morning of the FBT at a single laboratory. Primary outcomes included the LBR, with secondary outcomes encompassing clinical pregnancy rates, EMRs, and neonatal outcomes (birth weight and term of delivery). Patients were categorized into three groups based on E2 levels: &amp;lt;25th centile (&amp;lt;122\u2009pg\/ml), between 25th and 75th centile (122\u2013312\u2009pg\/ml), and &amp;gt;75th centile (\u2265313\u2009pg\/ml), and analyzed using univariate and multivariate logistic regression models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>Of the 2364 patients, 590 were in the \u2018&amp;lt;122\u2009pg\/ml\u2019 group, 1184 in the \u2018122\u2013312\u2009pg\/ml\u2019 group, and 590 in the \u2018\u2265313\u2009pg\/ml\u2019 group. The median (interquartile range) E2 level in the entire study population was 195.3\u2009pg\/ml (122.1\u2013312.8). The LBRs across the E2 level groups were 33.7%, 31.6%, and 31.0%. Crude and adjusted odds ratios (ORs) showed no significant differences in LBR between the \u2018&amp;lt;122\u2009pg\/ml\u2019 and \u2018\u2265313\u2009pg\/ml\u2019 groups compared to the \u2018122\u2013312\u2009pg\/ml\u2019 reference group (adjusted OR 0.9, 95% CI 0.72\u20131.14 and 0.9, 95% CI 0.69\u20131.09, respectively). The EMRs for the groups were 25.5%, 24.6%, and 30.3%, respectively. While crude analysis showed no differences between the groups, the multivariable analysis indicated that the \u2018\u2265313\u2009pg\/ml\u2019 group had a significantly higher risk of early miscarriage compared to the reference group (adjusted OR 1.5, 95% CI 1.06\u20132.18). No significant differences were observed in clinical pregnancy rates or neonatal outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>The primary limitation is the study\u2019s retrospective design, which introduces risks of selection and confusion bias, although multivariable analysis was employed to mitigate these issues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>Managing high serum E2 levels on the day of the FBT may enhance ART outcomes. Future research should aim to define optimal E2 thresholds for HRT-FBT cycles and develop personalized treatment protocols that account for individual patient variability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>No funding was received. The authors have no conflicts of interest.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deaf037","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T11:30:29Z","timestamp":1741347029000},"page":"876-884","source":"Crossref","is-referenced-by-count":1,"title":["High serum estradiol levels on the day of frozen blastocyst transfer are associated with increased early miscarriage rates in artificial cycles using transdermal estrogens"],"prefix":"10.1093","volume":"40","author":[{"given":"Chlo\u00e9","family":"Maignien","sequence":"first","affiliation":[{"name":"Facult\u00e9 de Sant\u00e9, Universit\u00e9 de Paris , Paris,","place":["France"]},{"name":"Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-H\u00f4pitaux de 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