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Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (<jats:italic>n<\/jats:italic>\u2009=\u200965), the HRT group (<jats:italic>n<\/jats:italic>\u2009=\u2009194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist\u2013HRT) group (<jats:italic>n<\/jats:italic>\u2009=\u2009290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The live birth rate in the GnRH agonist\u2013HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist\u2013HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381\u20130.926; <jats:italic>P<\/jats:italic>\u2009=\u20090.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181\u20130.796; <jats:italic>P<\/jats:italic>\u2009=\u20090.010).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The GnRH agonist\u2013HRT protocol improves the live birth rate in frozen\u2013thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist\u2013HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist\u2013HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>This research protocol was approved by the hospital institutional ethics committee (No. 2021002).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12958-022-00897-3","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T11:06:34Z","timestamp":1643886394000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen\u2013thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure"],"prefix":"10.1186","volume":"20","author":[{"given":"Dan","family":"Pan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanzi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"897_CR1","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1093\/humrep\/deaa134","volume":"35","author":"Z Ben Rafael","year":"2020","unstructured":"Ben Rafael Z. 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