{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:44:52Z","timestamp":1778795092025,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The overall cumulative live birth rate (CLBR) of poor ovarian responders (POR) is extremely low. Minimal ovarian stimulation (MOS) provides a relatively realistic solution for ovarian stimulation in POR. Our study aimed to investigate whether multiple MOS strategies resulted in higher CLBR compared to conventional gonadotropin releasing hormone (GnRH) antagonists in POR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study included 699 patients (1,058 cycles) from one center, who fulfilled the Bologna criteria between 2010 and 2018. Overall, 325 women (325 cycles) were treated with one-time conventional GnRH antagonist ovarian stimulation (GnRH-antagonist). Another 374 patients (733 cycles) were treated with multiple MOS including natural cycles. CLBR and time-and-cost-benefit analyses were compared between these two groups of women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GnRH antagonists provided more retrieved oocytes, meiosis II oocytes, fertilized oocytes, and more viable embryos compared to both the first MOS (p &amp;lt; 0.001) and the cumulative corresponding numbers in multiple MOSs (p &amp;lt; 0.001). For the first <jats:italic>in vitro<\/jats:italic> fertilization (IVF) cycle, GnRH antagonists resulted in higher CLBR than MOS [12.92 <jats:italic>versus<\/jats:italic> 4.54%, adjusted OR (odds ratio) 2.606; 95% CI (confidence interval) 1.386, 4.899, p = 0.003]. The one-time GnRH-antagonist induced comparable CLBR (12.92 <jats:italic>versus<\/jats:italic> 7.92%, adjusted OR 1.702; 95% CI 0.971, 2.982, p = 0.063), but a shorter time to live birth [9 (8, 10.75) months <jats:italic>versus<\/jats:italic> 11 (9, 14) months, p = 0.014] and similar financial expenditure compared to repeated MOS [20,838 (17,953, 23,422) \u00a5 <jats:italic>versus<\/jats:italic> 21,261.5 (15,892.5, 35,140.25) \u00a5, p = 0.13].<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both minimal ovarian stimulation (MOS) and GnRH-antagonists provide low chances of live birth in poor responders. The GnRH antagonist protocol is considered a suitable choice for PORs with comparable CLBR, shorter times to live birth, and similar financial expenditure compared to repeated MOS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2020.605939","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T20:09:04Z","timestamp":1610654944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Cumulative Live Birth Rate and Cost-Effectiveness Analysis of Gonadotropin Releasing Hormone-Antagonist Protocol and Multiple Minimal Ovarian Stimulation in Poor Responders"],"prefix":"10.3389","volume":"11","author":[{"given":"Yuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjia","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-015-0476-4","article-title":"Live birth rates in the different combinations of the Bologna criteria poor ovarian responders: a validation study","volume":"32","author":"La Marca","year":"2015","journal-title":"J Assist Reprod Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der092","article-title":"ESHRE consensus on the definition of \u2018poor response\u2019 to ovarian stimulation for in vitro fertilization: the Bologna criteria","volume":"26","author":"Ferraretti","year":"2011","journal-title":"Hum Reprod (Oxford England)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz046","article-title":"Adjuvant treatment strategies in ovarian stimulation for poor responders undergoing IVF: a systematic review and network meta-analysis","volume":"26","author":"Zhang","year":"2020","journal-title":"Hum Reprod Update"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00892","article-title":"Low Dose Growth Hormone Adjuvant Treatment With Ultra-Long Ovarian Stimulation Protocol in Poor Responders Showed Non-inferior Pregnancy Outcome Compared With Normal Responders","volume":"10","author":"Lee","year":"2019","journal-title":"Front Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq220","article-title":"Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study","volume":"25","author":"Wiser","year":"2010","journal-title":"Hum Reprod (Oxford England)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/humupd\/dmr037","article-title":"The poor responder in IVF: is the prognosis always poor?: a systematic review","volume":"18","author":"Oudendijk","year":"2012","journal-title":"Hum Reprod Update"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-012-2522-0","article-title":"A comparative study of luteal estradiol pre-treatment in GnRH antagonist protocols and in micro dose flare protocols for poor-responding patients","volume":"287","author":"Davar","year":"2013","journal-title":"Arch Gynecol Obstet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den107","article-title":"Flexible GnRH antagonist versus flare-up GnRH agonist protocol in poor responders treated by IVF: a randomized controlled trial","volume":"23","author":"Lainas","year":"2008","journal-title":"Hum Reprod (Oxford England)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.07.006","article-title":"Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study","volume":"92","author":"Demirol","year":"2009","journal-title":"Fertil Steril"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.03.057","article-title":"Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection-embryo transfer cycle","volume":"91","author":"Kahraman","year":"2009","journal-title":"Fertil Steril"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.09.012","article-title":"Luteal phase after conventional stimulation in the same ovarian cycle might improve the management of poor responder patients fulfilling the Bologna criteria: a case series","volume":"113","author":"Vaiarelli","year":"2020","journal-title":"Fertil Steril"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dex318","article-title":"Individualized versus standard FSH dosing in women starting IVF\/ICSI: an RCT. 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