{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T09:00:39Z","timestamp":1765875639918,"version":"3.48.0"},"reference-count":20,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hunan Provincial Grant for Innovative Province Construction","award":["2019SK4012"],"award-info":[{"award-number":["2019SK4012"]}]},{"name":"Research Grant of CITIC-Xiangya","award":["YNXM-202203"],"award-info":[{"award-number":["YNXM-202203"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,7,26]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hormone replacement treatment (HRT) is the most commonly used endometrial preparation protocol for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). However, studies have found that HRT may increase the risk of hypertensive disorders of pregnancy and some obstetric complications. Letrozole is a new first-line ovulation induction drug for PCOS and can effectively induce spontaneous ovulation by reducing oestrogen levels. However, letrozole is still rarely used in FET and has only been reported in a few studies in Asian populations. High-quality, well-powered randomised controlled trials (RCTs) comparing HRT and letrozole-stimulated protocols are lacking. The aim of this study is to compare the efficacy and safety of two protocols in patients with PCOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre, open-label RCT in four reproductive medical centres in China. In total, 1078\u2009women with PCOS will be randomised (1:1) to the letrozole-stimulated or HRT group in their first FET cycle and their pregnancy and perinatal outcomes during this cycle will be followed up and analysed. The primary outcome is live birth. Secondary outcomes are cycle cancellation rate, biochemical pregnancy, clinical pregnancy, miscarriage, ectopic pregnancy, obstetric and perinatal complications, neonatal complications and birth weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was obtained from the Institutional Review Board of Reproductive and Genetic Hospital of CITIC-XIANGYA (LL-SC-2022-001). Written informed consent will be obtained from each participant. The findings will be disseminated through conference presentations and publication in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05227391\">NCT05227391<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-072021","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T11:10:34Z","timestamp":1692270634000},"page":"e072021","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Live birth after letrozole-stimulated cycles versus hormone replacement treatment cycles for the first frozen embryo transfer in women with polycystic ovary syndrome: protocol for a multicentre randomised controlled trial"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct05227391","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05227391","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-6432","authenticated-orcid":false,"given":"Xiaojuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, Central South University, Changsha, Hunan, China"},{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital CITIC Xiangya, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital CITIC Xiangya, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-5272","authenticated-orcid":false,"given":"Cuilian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Rong","family":"Feng","sequence":"additional","affiliation":[{"name":"Guizhou Provincial People's Hospital, Guiyang, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, First People's Hospital of Yunnan, Kunming, Yunnan, China"},{"name":"Reproductive Medical Center of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaodi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Ma","sequence":"additional","affiliation":[{"name":"Guizhou Provincial People's Hospital, Guiyang, Guizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuerong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, First People's Hospital of Yunnan, Kunming, Yunnan, China"},{"name":"Reproductive Medical Center of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge","family":"Lin","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital CITIC Xiangya, Changsha, China"},{"name":"Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University School of Basic Medical Science, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Gong","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital CITIC Xiangya, Changsha, China"},{"name":"Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University School of Basic Medical Science, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"2025121600562360000_13.8.e072021.1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy033"},{"key":"2025121600562360000_13.8.e072021.2","article-title":"Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes","volume":"10","author":"Glujovsky","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"2025121600562360000_13.8.e072021.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2018.24"},{"key":"2025121600562360000_13.8.e072021.4","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/humrep\/deac073","article-title":"Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis","volume":"37","author":"Busnelli","year":"2022","journal-title":"Hum Reprod"},{"key":"2025121600562360000_13.8.e072021.5","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.k4810","article-title":"Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases","volume":"364","author":"Vinogradova","year":"2019","journal-title":"BMJ"},{"key":"2025121600562360000_13.8.e072021.6","doi-asserted-by":"publisher","DOI":"10.1021\/jm00173a001"},{"key":"2025121600562360000_13.8.e072021.7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-4235"},{"key":"2025121600562360000_13.8.e072021.8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.fertnstert.2008.10.009","article-title":"Comparison of endocrine and ultrasound profiles during ovulation induction with clomiphene citrate and letrozole in ovulatory volunteer women","volume":"93","author":"Jirge","year":"2010","journal-title":"Fertil Steril"},{"key":"2025121600562360000_13.8.e072021.9","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1056\/NEJMoa1313517","article-title":"Letrozole versus clomiphene for infertility in the polycystic ovary syndrome","volume":"371","author":"Legro","year":"2014","journal-title":"N Engl J Med"},{"key":"2025121600562360000_13.8.e072021.10","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey256"},{"key":"2025121600562360000_13.8.e072021.11","doi-asserted-by":"crossref","DOI":"10.1186\/s12958-022-00931-4","article-title":"Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome","volume":"20","author":"Zhang","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"2025121600562360000_13.8.e072021.12","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.fertnstert.2019.04.014","article-title":"Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome","volume":"112","author":"Zhang","year":"2019","journal-title":"Fertil Steril"},{"key":"2025121600562360000_13.8.e072021.13","doi-asserted-by":"crossref","DOI":"10.1016\/j.fertnstert.2005.07.230","article-title":"The outcome of 150 babies following the treatment with Letrozole or Letrozole and Gonadotropins","volume":"84","author":"Biljan","year":"2005","journal-title":"Fertility and Sterility"},{"key":"2025121600562360000_13.8.e072021.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2003.10.004"},{"key":"2025121600562360000_13.8.e072021.15","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmg044"},{"key":"2025121600562360000_13.8.e072021.16","article-title":"ACOG committee opinion no. 738: Aromatase inhibitors in gynecologic practice","volume":"131","year":"2018","journal-title":"Obstet Gynecol"},{"key":"2025121600562360000_13.8.e072021.17","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1093\/humrep\/dex285","article-title":"Frozen embryo transfer: a review on the optimal endometrial preparation and timing","volume":"32","author":"Mackens","year":"2017","journal-title":"Hum Reprod"},{"key":"2025121600562360000_13.8.e072021.18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/07853890.2017.1294258","article-title":"Population-based birth weight reference percentiles for Chinese twins","volume":"49","author":"Dai","year":"2017","journal-title":"Ann Med"},{"key":"2025121600562360000_13.8.e072021.19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0104779","article-title":"Birth weight reference percentiles for Chinese","volume":"9","author":"Dai","year":"2014","journal-title":"PLoS One"},{"key":"2025121600562360000_13.8.e072021.20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.fertnstert.2019.04.014","article-title":"Letrozole use during frozen embryo transfer cycles in women with polycystic ovary syndrome","volume":"112","author":"Zhang","year":"2019","journal-title":"Fertility and Sterility"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-072021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:56:37Z","timestamp":1765875397000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-072021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":20,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,17]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/bmjopen-2023-072021"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-072021","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}