Comparison of different ovarian stimulation protocols on pregnancy outcome in women with endometriosis undergoing frozen embryo transfer

In: European Journal of Medical Research · 2026 · doi:10.1186/s40001-026-05250-7 · W7214113966
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In women with endometriosis undergoing frozen embryo transfer, the GnRH-antagonist protocol yielded lower live birth rates than the long GnRH-agonist protocol, while mild stimulation resulted in lower biochemical pregnancy and high-quality embryo rates compared to the agonist approach.

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This retrospective study evaluated the efficacy of three controlled ovarian stimulation protocols among 636 women with endometriosis undergoing frozen embryo transfer between 2015 and 2022. Using inverse probability of treatment weighting to adjust for baseline characteristics, the researchers compared live birth rates across long GnRH-agonist, GnRH-antagonist, and mild-stimulation groups. The analysis revealed that the GnRH-antagonist protocol yielded significantly lower live birth rates than the GnRH-agonist protocol, whereas the mild-stimulation approach showed comparable live birth outcomes but reduced biochemical pregnancy and high-quality embryo rates. Consequently, the authors concluded that both the GnRH-agonist and mild-stimulation protocols are more favorable for achieving live births in patients with stage III–IV endometriosis compared to the antagonist regimen. This paper is centrally about endometriosis — specifically focusing on optimizing assisted reproductive technology outcomes for patients with this condition.

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Abstract

This study aimed to evaluate the efficacy of three distinct controlled ovarian stimulation (COS) protocols—long GnRH-agonist (GnRH-a) protocol, GnRH-antagonist (GnRH-ant) protocol, and mild-ovarian stimulation protocol—in endometriosis patients undergoing frozen embryo transfer therapy. The research involved 636 women with endometriosis during 2015–2022. These patients received different COS protocols, including 118 cases with GnRH-a, 295 with GnRH-ant, 223 with mild‑stimulation protocol. Inverse probability of treatment weighting was used to adjust baseline features to reduce bias. The pregnancy outcomes were evaluated among the groups. In the analysis, the live birth rate was lower in the GnRH-ant group (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47–0.83, P = 0.001) than in the GnRH-a group with no differences in other key pregnancy outcomes. The mild group showed no difference in live birth rate vs. GnRH-a group, but lower biochemical pregnancy rate (OR 0.73, 95% CI 0.54–0.98, P = 0.04) and high-quality embryo rate (OR 0.69, 95% CI 0.51–0.94, P = 0.02). For patients with stage III–IV endometriosis undergoing FET, mild‑stimulation and GnRH-a protocols are more favorable than GnRH-ant due to higher live birth rates.
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Abstract

Purpose This study aimed to evaluate the efficacy of three distinct controlled ovarian stimulation (COS) protocols—long GnRH-agonist (GnRH-a) protocol, GnRH-antagonist (GnRH-ant) protocol, and mild-ovarian stimulation protocol—in endometriosis patients undergoing frozen embryo transfer therapy.

Methods

The research involved 636 women with endometriosis during 2015–2022. These patients received different COS protocols, including 118 cases with GnRH-a, 295 with GnRH-ant, 223 with mild‑stimulation protocol. Inverse probability of treatment weighting was used to adjust baseline features to reduce bias. The pregnancy outcomes were evaluated among the groups.

Results

In the analysis, the live birth rate was lower in the GnRH-ant group (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.47–0.83, P = 0.001) than in the GnRH-a group with no differences in other key pregnancy outcomes. The mild group showed no difference in live birth rate vs. GnRH-a group, but lower biochemical pregnancy rate (OR 0.73, 95% CI 0.54–0.98, P = 0.04) and high-quality embryo rate (OR 0.69, 95% CI 0.51–0.94, P = 0.02).

Conclusions

For patients with stage III–IV endometriosis undergoing FET, mild‑stimulation and GnRH-a protocols are more favorable than GnRH-ant due to higher live birth rates. Similar content being viewed by others Abbreviations - IVF: - In vitro fertilization - FET: - Frozen-thawed embryo transfer - OHSS: - Ovarian hyperstimulation syndrome - GnRH: - Gonadotropin-releasing hormone - RCTs: - Randomized controlled trials - HMG: - Human menopausal gonadotrophin - FSH: - Follicle-stimulating hormone - hCG: - Human chorionic gonadotropin - BMI: - Body mass index - E2: - Estradiol - P: - Progesterone - IPTW: - Inverse probability of treatment weighting - HRT: - Hormone replacement therapy - OR: - Odds ratio - CI: - Confidence interval

Acknowledgements

We would like to thank clinicians and statisticians for their help. Funding This work was supported by grants from the National Natural Science Foundation of China (No. 82371642), Shanghai Science and Technology Commission (No. 23DZ2202100), the start funding from Shanghai Tongji Hospital for ZZ (No. RCQD2307), New Round of Xuzhou “Peng cheng Talent Program"–High-level Health Care Talent Recruitment and Development Project (Project Number: 2025RC12) for MB. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics approval and consent to participate The studies involving human participants were reviewed and approved by the Institutional Review Board and Ethics Committee of Xuzhou Maternity and Child Health Care Hospital ([2023] Reproductive Medicine Ethic Approved No.06). Participants in this study did not require written informed consent according to national law and institutional standards. Competing interests The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Luo, Y., Yu, L., Yu, J. et al. Comparison of different ovarian stimulation protocols on pregnancy outcome in women with endometriosis undergoing frozen embryo transfer. Eur J Med Res (2026). https://doi.org/10.1186/s40001-026-05250-7 Received: Accepted: Published: DOI: https://doi.org/10.1186/s40001-026-05250-7

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