Optimal range of serum progesterone on endometrial transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study

Optimal range of serum progesterone on endometrial transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Optimal range of serum progesterone on endometrial transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study Jingshu Fu, Xiaoling Gu, Minyan Yu, Lingna Peng, Jian Song, Xiaoli Sun, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9423110/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background The predictive value of serum progesterone on the day of endometrial transformation in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles remains unclear, and its effect may vary by protocol. This study aimed to evaluate its impact and compare it between standard and down-regulated HRT protocols. Methods This retrospective study of 1,073 cycles defined a progesterone cutoff of 0.56 ng/mL via ROC analysis. Cycles were categorized into low (< 0.56 ng/mL) and high (≥ 0.56 ng/mL) subgroups, with multivariate logistic regression identifying predictors of clinical pregnancy. A secondary three-tier stratification (< 0.56, 0.56–1.0, ≥ 1.0 ng/mL) was performed to define the optimal therapeutic window. Results Clinical pregnancy rates did not differ significantly between progesterone subgroups in the overall cohort or the standard HRT group. However, in down-regulated HRT cycles, the high progesterone level (≥ 0.56 ng/mL) was associated with higher clinical pregnancy rate (62.4% vs. 48.9%, P = 0.012) and was an independent predictor of clinical pregnancy exclusively in down-regulated cycles (OR = 3.682, 95% CI: 1.575–8.612, P = 0.003). Three-tier analysis showed a non-linear relationship, with rates lowest at < 0.56 ng/mL (48.92%), peaking at 0.56–1.0 ng/mL (63.55%), and declining at ≥ 1.0 ng/mL (55.56%, P = 0.035), identifying 0.56–1.0 ng/mL as the optimal range. Conclusion The predictive value of serum progesterone is protocol-specific. In down-regulated HRT-FET cycles, a level of 0.56–1.0 ng/mL on transformation day is optimal, suggesting routine monitoring may guide individualized luteal support. Hospital Medicine Hormone replacement therapy Frozen-thawed embryo transfer Progesterone Endometrial transformation Clinical pregnancy Down-regulation Figures Figure 1 Figure 2 Figure 3 Figure 3 Figure 4 Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9423110","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":624177984,"identity":"83b2b6f8-9ccd-4629-96a6-d7d8af63615e","order_by":0,"name":"Jingshu Fu","email":"","orcid":"","institution":"1. 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transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Affiliated Hospital of Nantong University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hormone replacement therapy, Frozen-thawed embryo transfer, Progesterone, Endometrial transformation, Clinical pregnancy, Down-regulation","lastPublishedDoi":"10.21203/rs.3.rs-9423110/v2","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9423110/v2","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe predictive value of serum progesterone on the day of endometrial transformation in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles remains unclear, and its effect may vary by protocol. This study aimed to evaluate its impact and compare it between standard and down-regulated HRT protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study of 1,073 cycles defined a progesterone cutoff of 0.56 ng/mL via ROC analysis. Cycles were categorized into low (\u0026lt; 0.56 ng/mL) and high (≥ 0.56 ng/mL) subgroups, with multivariate logistic regression identifying predictors of clinical pregnancy. A secondary three-tier stratification (\u0026lt; 0.56, 0.56–1.0, ≥ 1.0 ng/mL) was performed to define the optimal therapeutic window.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical pregnancy rates did not differ significantly between progesterone subgroups in the overall cohort or the standard HRT group. However, in down-regulated HRT cycles, the high progesterone level (≥ 0.56 ng/mL) was associated with higher clinical pregnancy rate (62.4% vs. 48.9%, P = 0.012) and was an independent predictor of clinical pregnancy exclusively in down-regulated cycles (OR = 3.682, 95% CI: 1.575–8.612, P = 0.003). Three-tier analysis showed a non-linear relationship, with rates lowest at \u0026lt; 0.56 ng/mL (48.92%), peaking at 0.56–1.0 ng/mL (63.55%), and declining at ≥ 1.0 ng/mL (55.56%, P = 0.035), identifying 0.56–1.0 ng/mL as the optimal range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe predictive value of serum progesterone is protocol-specific. In down-regulated HRT-FET cycles, a level of 0.56–1.0 ng/mL on transformation day is optimal, suggesting routine monitoring may guide individualized luteal support.\u003c/p\u003e","manuscriptTitle":"Optimal range of serum progesterone on endometrial transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-04-21 17:46:44","doi":"10.21203/rs.3.rs-9423110/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2026-04-16 09:14:49","doi":"10.21203/rs.3.rs-9423110/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7323077e-e518-47e5-8524-ca7cf45ca388","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66433996,"name":"Hospital Medicine"}],"tags":[],"updatedAt":"2026-04-16T09:14:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 17:46:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-9423110","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9423110","identity":"rs-9423110","version":["v2"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}