{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:10:03Z","timestamp":1790331003422,"version":"4.1.0"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>In women, recognition of sequential follicular waves throughout the menstrual cycle established the physiologic basis for random-start ovarian stimulation outside the conventional early follicular phase and for DuoStim within a single cycle. These approaches reduce treatment delays and, in the case of DuoStim, provide two oocyte-retrieval opportunities within a shortened interval, thereby benefiting fertility preservation and women with restricted reproductive windows. However, stimulation begins under ovarian physiologic and endocrine conditions that may differ even within the same menstrual-cycle phase according to follicular-wave stage, dominant follicle status, the recruitable follicular cohort, and corpus luteum maturity and function. Such heterogeneity at stimulation initiation may contribute to variability in ovarian responsiveness and limit the predictability of ovarian-response outcomes. This review integrates clinical evidence for random-start ovarian stimulation and DuoStim in women with basic and applied findings from cattle and mares, while recognizing the human protocols as related but physiologically distinct. In monovulatory domestic animal models, follicular-wave emergence, dominant follicle status, and luteal function can be characterized and experimentally manipulated before gonadotropin stimulation, permitting mechanistic relationships to be evaluated more directly than in women. Spontaneous-cycle random-start stimulation is also distinguished from the second stimulation of DuoStim, which begins in a treatment-modified, post-retrieval luteal environment following follicular-phase stimulation, final oocyte-maturation triggering, and oocyte retrieval. Comparative studies demonstrate similarities in follicular-wave dynamics among women, cattle, and mares. Experimental and production-management studies in cattle provide direct evidence that dominant follicle status and corpus luteum maturity and function influence follicular recruitment, endocrine conditions, and ovarian response to gonadotropin stimulation. Studies in mares provide complementary mechanistic evidence concerning control of wave emergence, follicle selection, and ovulation. Although they do not establish equivalent regulation in women, these comparative findings provide a mechanistic framework for identifying measurable follicular, luteal, and endocrine variables that may explain response variability, improve prediction, and inform optimization of stimulation strategies. Accordingly, the central hypothesis is that menstrual-cycle phase alone does not adequately characterize the heterogeneous ovarian environment at stimulation initiation. Evidence is strongest for ovarian-response and time-efficiency outcomes, whereas evidence for improved downstream reproductive outcomes, particularly pregnancy and live birth, remains limited and variable.<\/jats:p>","DOI":"10.3389\/fendo.2026.1980858","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:51:06Z","timestamp":1790329866000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ovarian responsiveness during random-start stimulation and DuoStim in women: comparative insights from domestic animal models"],"prefix":"10.3389","volume":"17","author":[{"given":"Don R.","family":"Bergfelt","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Lincoln Memorial University","place":["Orange Park, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoaa052","article-title":"ESHRE guideline: female fertility preservation","volume":"4","author":"Anderson","year":"2020","journal-title":"Hum Reprod Open"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.09.013","article-title":"Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion","volume":"112","year":"2019","journal-title":"Fertil Steril"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(03)00544-2","article-title":"A new model for ovarian follicular development during the human menstrual cycle","volume":"80","author":"Baerwald","year":"2003","journal-title":"Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.017772","article-title":"Characterization of ovarian follicular wave dynamics in women","volume":"69","author":"Baerwald","year":"2003","journal-title":"Biol Reprod"},{"key":"B5","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1093\/humupd\/dmr039","article-title":"Ovarian antral folliculogenesis during the human menstrual cycle: a review","volume":"18","author":"Baerwald","year":"2012","journal-title":"Hum Reprod Update"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.07.008","article-title":"Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation","volume":"114","author":"Baerwald","year":"2020","journal-title":"Fertil Steril"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.07.1992","article-title":"Effective method for emergency fertility preservation: random-start controlled ovarian stimulation","volume":"100","author":"Cakmak","year":"2013","journal-title":"Fertil Steril"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/GCO.0000000000000180","article-title":"Random-start ovarian stimulation in patients with cancer","volume":"27","author":"Cakmak","year":"2015","journal-title":"Curr Opin Obstet Gynecol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2023.103337","article-title":"Random start controlled ovarian stimulation prior to gonadotoxic therapies in women with cancer: a systematic review and meta-analysis","volume":"47","author":"S\u00f6nmezer","year":"2023","journal-title":"Reprod BioMed Online"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2014.08.009","article-title":"Double stimulations during the follicular and luteal phases of poor responders in IVF\/ICSI programmes (Shanghai protocol)","volume":"29","author":"Kuang","year":"2014","journal-title":"Reprod BioMed Online"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1016\/j.fertnstert.2016.03.002","article-title":"Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation","volume":"105","author":"Ubaldi","year":"2016","journal-title":"Fertil Steril"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/03009734.2020.1734694","article-title":"DuoStim \u2013 a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. 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