{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:57Z","timestamp":1753891017136,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"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:sec><jats:title>Purpose<\/jats:title><jats:p>To compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in \u201cunpredictable\u201d poor ovarian response (POR) women undergoing <jats:italic>in vitro<\/jats:italic> fertilization\/intracytoplasmic sperm injection (IVF\/ICSI) treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective single-center cohort study was conducted on 67 patients with \u201cunpredictable\u201d POR in their first IVF\/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF\/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E<jats:sub>2<\/jats:sub>) on day of hCG trigger, and clinical pregnant outcomes were studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E<jats:sub>2<\/jats:sub>, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in \u201cunpredictable\u201d poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.739773","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T15:49:01Z","timestamp":1634140141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Follicular Phase Human Chorionic Gonadotropin Addition May Improve the Outcomes of In Vitro Fertilization\/Intracytoplasmic Sperm Injection in Patients With \u201cUnpredictable\u201d Poor Response to Gonadotropin-Releasing Hormone Antagonist Protocol"],"prefix":"10.3389","volume":"12","author":[{"given":"Chunhui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangrong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zexuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bolan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)81407-0","article-title":"Comparison of Different Doses of Gonadotropin-Releasing Hormone Antagonist Cetrorelix During Controlled Ovarian Hyperstimulation","volume":"67","author":"Albano","year":"1997","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev038","article-title":"Recombinant Follicle-Stimulating Hormone and Recombinant Luteinizing Hormone Versus Recombinant Follicle-Stimulating Hormone Alone During GnRH Antagonist Ovarian Stimulation in Patients Aged \u226535 Years: A Randomized Controlled Trial","volume":"30","author":"Vuong","year":"2015","journal-title":"Hum Reprod"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.01.021","article-title":"Low-Dose Human Chorionic Gonadotropin Alone Can Complete Follicle Maturity: Successful Application to Modified Natural Cycle","volume":"105","author":"Paulson","year":"2016","journal-title":"Vitro Fertilization Fertil Steril"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.7.1788","article-title":"Effects of Profound Suppression of Luteinizing Hormone During Ovarian Stimulation on Follicular Activity, Oocyte and Embryo Function in Cycles Stimulated With Purified Follicle Stimulating Hormone","volume":"13","author":"Fleming","year":"1998","journal-title":"Hum Reprod"},{"key":"B5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.rbmo.2011.03.023","article-title":"Current Opinion on Use of Luteinizing Hormone Supplementation in Assisted Reproduction Therapy: An Asian Perspective","volume":"23","author":"Wong","year":"2011","journal-title":"Reprod BioMed Online"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des256","article-title":"A Randomized Controlled Doseresponse Pilot Study of Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization","volume":"27","author":"Thuesen","year":"2012","journal-title":"Hum Reprod"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.02.110","article-title":"Ovarian Stimulation With Daily Late Follicular Phase Administration of Low-Dose Human Chorionic Gonadotropin for In Vitro Fertilization: A Prospective, Randomized Trial","volume":"86","author":"Serafini","year":"2006","journal-title":"Fertil Steril"},{"key":"B8","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/1477-7827-7-110","article-title":"Early hCG Addition to rFSH for Ovarian Stimulation in IVF Provides Better Results and the cDNA Copies of the hCG Receptor May Be an Indicator of Successful Stimulation","volume":"13","author":"Drakakis","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det266","article-title":"Recombinant LH Supplementation to a Standard GnRH Antagonist Protocol in Women of 35 Years or Older Undergoing IVF\/ICSI: A Randomized Controlled Multicentre Study","volume":"28","author":"K\u00f6nig","year":"2013","journal-title":"Hum Reprod"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der092","article-title":"ESHRE Consensus on the Definition of \u2018Poor Response to Ovarian Stimulation for In Vitro Fertilization: The Bologna Criteria","volume":"26","author":"Ferraretti","year":"2011","journal-title":"Hum Reprod"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2174\/138920112799361972","article-title":"Possibilities and Limits of Ovarian Reserve Testing in ART","volume":"92","author":"Marca","year":"2012","journal-title":"Curr Pharm Biotechnol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.06.039","article-title":"The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology","volume":"110","author":"Zegers-Hochschild","year":"2009","journal-title":"Hum Reprod"},{"key":"B13","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/1477-7827-7-101","article-title":"Biological Versus Chronological Ovarian Age: Implications for Assisted Reproductive Technology","volume":"7","author":"Alviggi","year":"2009","journal-title":"Reprod Biol Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2014.932342","article-title":"Recombinant LH Administration in Subsequent Cycle After \u2018Unexpected\u2019 Poor Response to Recombinant FSH Monotherapy","volume":"30","author":"Papaleo","year":"2014","journal-title":"Gynecol Endocrinol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/cen.13481","article-title":"The Effects of Low-Dose Human Chorionic Gonadotropin Combined With Human Menopausal Gonadotropin Protocol on Women With Hypogonadotropic Hypogonadism Undergoing Ovarian Stimulation for Vitro Fertilization","volume":"88","author":"Jiang","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jogoh.2019.02.012","article-title":"The Impact of HCG in IVF Treatment: Does It Depend on Age or on Protocol","volume":"48","author":"Theofanakis","year":"2019","journal-title":"J Gynecol Obstet Hum Reprod"},{"key":"B17","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1477-7827-12-17","article-title":"Recombinant Human Follicle-Stimulating Hormone (r-hFSH) Plus Recombinant Luteinizing Hormone Versus r-hFSH Alone for Ovarian Stimulation During Assisted Reproductive Technology: Systematic Review and Meta-Analysis","volume":"12","author":"Lehert","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)55968-8","article-title":"Luteinizing Hormone: Its Role, Mechanism of Action, and Detrimental Effects When Hypersecreted During the Follicular Phase","volume":"59","author":"Shoham","year":"1993","journal-title":"Fertil Steril"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/8.6.543","article-title":"The Use of LH Activity to Drive Folliculogenesis: Exploring Uncharted Territories in Ovulation Induction","volume":"8","author":"Filicori","year":"2002","journal-title":"Hum Reprod Update"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(03)00594-6","article-title":"Comparison of Controlled Ovarian Stimulation With Human Menopausal Gonadotropin or Recombinant Follicle-Stimulating Hormone","volume":"80","author":"Filicori","year":"2003","journal-title":"Fertil Steril"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.79.1.8027261","article-title":"Recombinant Human Follicle-Stimulating Hormone Stimulates Multiple Follicular Growth, But Minimal Estrogen Production in Gonadotropin-Releasing Hormone Antagonist-Treated Monkeys: Examining the Role of Luteinizing Hormone in Follicular Development and Ste","volume":"79","author":"Karnitis","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2081","article-title":"Androgens Stimulate Early Stages of Follicular Growth in the Primate Ovary","volume":"101","author":"Vendola","year":"1998","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.09.029","article-title":"The Precise Ovarian Volume Is Significantly Associated With Serum Concentrations of Antim\u00fcllerian Hormone, the Luteinizing Hormone\/Follicle-Stimulating Hormone Ratio, and Total Testosterone","volume":"113","author":"Wakimoto","year":"2020","journal-title":"Fertil Steril"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep378","article-title":"Assessment of Theca Cell Function Prior to Controlled Ovarian Stimulation: The Predictive Value of Serum Basal\/Stimulated Steroid Levels","volume":"25","author":"Hugues","year":"2010","journal-title":"Hum Reproduction"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.4.1589","article-title":"The Rise of Estradiol and Inhibin B After Acute Stimulation With Follicle-Stimulating Hormone Predict the Follicle Cohort Size in Women With Polycystic Ovary Syndrome, Regularly Menstruating Women With Polycystic Ovaries, and Regularly Menstruating Women With Normal Ovaries","volume":"86","author":"Elting","year":"2001","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.739773\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T15:49:03Z","timestamp":1634140143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.739773\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":25,"alternative-id":["10.3389\/fendo.2021.739773"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.739773","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2021,10,11]]},"article-number":"739773"}}