{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:55:46Z","timestamp":1790996146257,"version":"4.1.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec><jats:title>Importance<\/jats:title><jats:p>The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (\u22641500 IU and &amp;amp;lt;10 days), group 2 (\u22641500 IU and \u226510 days), group 3 (&amp;amp;gt;1500 IU and &amp;amp;lt;10 days), and group 4 (&amp;amp;gt;1 500 IU and \u226510 days). Group 1 served as the control group. Data were analyzed from June through August 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interventions<\/jats:title><jats:p>Blastocyst biopsy and PGT-A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcomes and measures<\/jats:title><jats:p>The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and relevance<\/jats:title><jats:p>In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03118141\">NCT03118141<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.4438","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:21:37Z","timestamp":1712071297000},"page":"e244438","source":"Crossref","is-referenced-by-count":7,"title":["Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer"],"prefix":"10.1001","volume":"7","author":[{"given":"Tianxiang","family":"Ni","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiran","family":"Cui","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China"},{"name":"Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"issue":"5","key":"zoi240194r1","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.fertnstert.2015.07.1151","article-title":"Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles.","volume":"104","author":"Baker","year":"2015","journal-title":"Fertil Steril"},{"issue":"2","key":"zoi240194r2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1210\/er.2005-0015","article-title":"The science behind 25 years of ovarian stimulation for in vitro fertilization.","volume":"27","author":"Macklon","year":"2006","journal-title":"Endocr Rev"},{"issue":"6","key":"zoi240194r3","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1093\/humrep\/16.6.1237","article-title":"Superovulation of female mice delays embryonic and fetal development.","volume":"16","author":"Van der Auwera","year":"2001","journal-title":"Hum Reprod"},{"issue":"3","key":"zoi240194r4","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1093\/humrep\/13.3.724","article-title":"Gonadotrophin stimulation of donor females decreases post-implantation viability of cultured one-cell hamster embryos.","volume":"13","author":"McKiernan","year":"1998","journal-title":"Hum Reprod"},{"issue":"2","key":"zoi240194r5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1095\/biolreprod25.2.253","article-title":"Superovulatory doses of pregnant mare serum gonadotropin cause delayed implantation and infertility in immature rats.","volume":"25","author":"Miller","year":"1981","journal-title":"Biol Reprod"},{"issue":"2","key":"zoi240194r6","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1530\/jrf.0.0960649","article-title":"Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice.","volume":"96","author":"Ertzeid","year":"1992","journal-title":"J Reprod Fertil"},{"issue":"4","key":"zoi240194r7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1007\/BF01204944","article-title":"Treatment with gonadotropins impaired implantation and fetal development in mice.","volume":"10","author":"Ertzeid","year":"1993","journal-title":"J Assist Reprod Genet"},{"issue":"9","key":"zoi240194r8","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1093\/humrep\/deq174","article-title":"Prospective cohort study in high responder oocyte donors using two hormonal stimulation protocols: impact on embryo aneuploidy and development.","volume":"25","author":"Rubio","year":"2010","journal-title":"Hum Reprod"},{"issue":"4","key":"zoi240194r9","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1093\/humrep\/del484","article-title":"Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.","volume":"22","author":"Baart","year":"2007","journal-title":"Hum Reprod"},{"issue":"10","key":"zoi240194r10","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1089\/gtmb.2018.0063","article-title":"Low gonadotropin dosage reduces aneuploidy in human preimplantation embryos: first clinical study in a UAE population.","volume":"22","author":"Sachdeva","year":"2018","journal-title":"Genet Test Mol Biomarkers"},{"issue":"10","key":"zoi240194r11","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1093\/humrep\/dey270","article-title":"Dosage of exogenous gonadotropins is not associated with blastocyst aneuploidy or live-birth rates in PGS cycles in Chinese women.","volume":"33","author":"Wu","year":"2018","journal-title":"Hum Reprod"},{"issue":"5","key":"zoi240194r12","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1093\/humrep\/deaa028","article-title":"No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: an analysis of 12?298 trophectoderm biopsies.","volume":"35","author":"Irani","year":"2020","journal-title":"Hum Reprod"},{"issue":"3","key":"zoi240194r13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1093\/humupd\/dmz050","article-title":"Chromosomal mosaicism in human blastocysts: the ultimate diagnostic dilemma.","volume":"26","author":"Popovic","year":"2020","journal-title":"Hum Reprod Update"},{"issue":"22","key":"zoi240194r14","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1056\/NEJMoa2103613","article-title":"Live birth with or without preimplantation genetic testing for aneuploidy.","volume":"385","author":"Yan","year":"2021","journal-title":"N Engl J Med"},{"issue":"6","key":"zoi240194r15","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/S0015-0282(00)00518-5","article-title":"Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer.","volume":"73","author":"Gardner","year":"2000","journal-title":"Fertil Steril"},{"issue":"1","key":"zoi240194r16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/humrep\/del316","article-title":"Aberrant DNA methylation of imprinted loci in superovulated oocytes.","volume":"22","author":"Sato","year":"2007","journal-title":"Hum Reprod"},{"issue":"1","key":"zoi240194r17","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.fertnstert.2010.04.037","article-title":"High follicle-stimulating hormone increases aneuploidy in human oocytes matured in vitro.","volume":"95","author":"Xu","year":"2011","journal-title":"Fertil Steril"},{"issue":"11","key":"zoi240194r18","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1093\/humrep\/dex299","article-title":"High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.","volume":"32","author":"Barash","year":"2017","journal-title":"Hum Reprod"},{"issue":"6","key":"zoi240194r19","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s10815-017-0909-3","article-title":"The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response.","volume":"34","author":"Sekhon","year":"2017","journal-title":"J Assist Reprod Genet"},{"issue":"1","key":"zoi240194r20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.rbmo.2020.09.025","article-title":"Prevalence, types and possible factors influencing mosaicism in IVF blastocysts: results from a single setting.","volume":"42","author":"Coll","year":"2021","journal-title":"Reprod Biomed Online"},{"issue":"6","key":"zoi240194r21","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/S0015-0282(16)56756-9","article-title":"High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization-embryo transfer.","volume":"61","author":"Stadtmauer","year":"1994","journal-title":"Fertil Steril"},{"issue":"6","key":"zoi240194r22","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1016\/j.fertnstert.2007.05.055","article-title":"Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization.","volume":"89","author":"Pal","year":"2008","journal-title":"Fertil Steril"},{"issue":"3","key":"zoi240194r23","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.fertnstert.2015.11.015","article-title":"Effects of in vitro fertilization and maternal characteristics on perinatal outcomes: a population-based study using siblings.","volume":"105","author":"Seggers","year":"2016","journal-title":"Fertil Steril"},{"key":"zoi240194r24","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.rbmo.2019.06.012","article-title":"PGDIS position statement on the transfer of mosaic embryos 2019.","volume":"39","author":"Cram","year":"2019","journal-title":"Reprod Biomed Online"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2816889\/ni_2024_oi_240194_1710966466.42921.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:21:41Z","timestamp":1712071301000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2816889"}},"subtitle":["A Secondary Analysis of a Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2024,4,2]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.4438","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,2]]}}}