{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:11:50Z","timestamp":1789621910385,"version":"build-2803163510"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Clinical Specialty Construction Project"},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["No. 2023-ZDLSF-48"],"award-info":[{"award-number":["No. 2023-ZDLSF-48"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the General Projects of Social Development in Shaanxi Province","award":["No. 2022SF-565"],"award-info":[{"award-number":["No. 2022SF-565"]}]},{"name":"the Xi\u2019an Municipal Science and Technology Bureau","award":["24YXYJ0175"],"award-info":[{"award-number":["24YXYJ0175"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec013\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Different endometrial preparation protocols are used prior to frozen-thawed embryo transfer (FET). Optimization of endometrial preparation protocols is mandatory to improve live birth rate and obstetric and perinatal outcomes. In the Comparison of Endometrial Preparation Protocols for Frozen Embryo Transfer (COMPETE) trial, our primary objective is to evaluate whether natural cycles (NCs) lead to a higher live birth rate after the first FET cycle compared to hormone replacement therapy (HRT) cycles in women with a regular ovulatory cycle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec014\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      We performed a single-center, parallel, open-label randomized controlled trial between December 2020 and December 2022 in a single assisted reproduction center in Xi\u2019an, China. Women with a regular menstrual cycle undergoing in vitro fertilization (IVF) scheduled for FET were randomly assigned (1:1) to endometrial preparation in the NC or with HRT, using a web-based electronic data capture system. The primary outcome was live birth rate after the initial FET. The analysis was conducted based on the intention-to-treat principle. Obstetric and perinatal outcomes in all randomly assigned women were reported in this study. We randomly assigned 902 women to receive either NC (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009448) or HRT (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009454). In the NC group, 101 women received HRT because of no ovulation, while in the HRT group, 29 women received NC because of spontaneous ovulation. The number of live births was 242 (54.0%) in the NC group versus 195 (43.0%) in the HRT group (absolute difference, 11.1 percentage points, 95% CI 4.6 to 17.5; risk ratio (RR) 1.26, 95% CI 1.10 to 1.44). Miscarriage rates (RR 0.61, 95% CI 0.41 to 0.89) and the antepartum hemorrhage rates (RR 0.63, 95%CI 0.42 to 0.93) were lower in the NC group, with other obstetric and perinatal outcomes not significantly different.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec015\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In women with a regular menstrual cycle undergoing FET, a strategy starting with NC endometrial preparation results in higher live birth rates than endometrial preparation with HRT. However, the permitted cross-over between arms limits certainty in directly assessing NC versus HRT efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec016\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry: ChiCTR2000040640.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004630","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T14:20:13Z","timestamp":1750861213000},"page":"e1004630","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Natural cycle versus hormone replacement therapy as endometrial preparation in ovulatory women undergoing frozen-thawed embryo transfer: The COMPETE open-label randomized controlled trial"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-4946","authenticated-orcid":true,"given":"Xitong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-0909","authenticated-orcid":true,"given":"Wentao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongran","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danmeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":true,"given":"Ben 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