Stop gonadotropin-releasing hormone-agonist protocol not superior to antagonist protocol on the outcomes of assisted reproductive techniques in poor responders: A randomized clinical trial.

Dashti S, Davar R, Emami F, Shamsi F, Mangoli E
International journal of reproductive biomedicine · 2026 · doi:10.18502/ijrm.v24i7.21586 · PMID:42774605 · PMC13594363
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This randomized trial found the stop GnRH-agonist protocol was not superior to the standard antagonist protocol for clinical or laboratory outcomes in poor ovarian responders, despite requiring higher gonadotropin doses and longer stimulation.

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This randomized clinical trial compared the efficacy of a stop GnRH-agonist protocol against a conventional GnRH-antagonist protocol for controlled ovarian hyperstimulation in 100 women classified as poor responders according to Bologna criteria. The study found no statistically significant differences between the two groups regarding primary outcomes such as clinical pregnancy, live birth rates, or secondary metrics including oocyte yield and embryo quality. Although the antagonist group showed numerically higher trends in some success metrics, the results indicate that the modified agonist strategy does not offer superior reproductive outcomes for this specific patient population. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

BackgroundPoor ovarian response remains one of the most challenging problems in assisted reproductive technology. Various stimulation protocols have been proposed to improve outcomes, including combined gonadotropin-releasing hormone (GnRH) agonist and antagonist strategies.ObjectiveTo compare the effectiveness of a stop GnRH-agonist protocol combined with a GnRH-antagonist protocol vs. a standard GnRH-antagonist protocol in poor ovarian responder (POR) cases.Materials and methodsThis randomized clinical trial was conducted on 100 women aged 18-44 yr diagnosed as POR according to the Bologna criteria. Participants were randomly allocated to either a GnRH-antagonist protocol (control group) or a combined Stop GnRH-agonist/GnRH-antagonist protocol (intervention group). The primary outcome was the clinical pregnancy rate. Secondary outcomes included the number of retrieved oocytes, embryo quality, chemical pregnancy, and live birth rate.ResultsNo statistically significant differences were observed between the 2 groups regarding chemical pregnancy, clinical pregnancy, or live birth rates. Laboratory outcomes, including the number of retrieved oocytes, metaphase II oocytes, and embryo quality, were also comparable. The intervention group required a significantly higher gonadotropin dose and had a longer stimulation duration (p < 0.01).ConclusionThe stop GnRH-agonist protocol did not demonstrate superiority over the GnRH-antagonist protocol in terms of laboratory or clinical outcomes in POR cases.
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The authors extend their appreciation to the Yazd Reproductive Sciences Institute and its staff. Additionally, they would like to express their sincere gratitude to the cases who participated in this study. This research received financial support from the Research and Clinical Center for Infertility at the Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran (code: 10132). Artificial intelligence tools, including ChatGPT were employed for grammar checking in specific sections.

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The authors declare that there is no conflict of interest.

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