Comparative efficacy of different IVF stimulation protocols in women with adenomyosis undergoing fresh embryo transfer: a systematic review and network meta-analysis

Introduction Adenomyosis is associated with reduced IVF success, yet the optimal ovarian stimulation strategy remains unclear. Although prolonged GnRH agonist suppression has been widely used, its benefit in fresh embryo transfer cycles is inconsistent, and potential differences between focal and diffuse adenomyosis are poorly defined. This network meta-analysis compared reproductive outcomes across commonly used stimulation protocols in women with adenomyosis undergoing fresh embryo transfer, with additional analysis according to disease subtype.

This network meta-analysis evaluates the effectiveness of commonly used stimulation protocols in women with adenomyosis undergoing fresh embryo transfer and examines whether outcomes differ between focal and diffuse disease.

We systematically searched PubMed, Scopus, and Google Scholar from inception to November 2025 for randomized trials and cohort studies comparing ovarian stimulation protocols (ultra-long GnRH agonist, long GnRH agonist, GnRH antagonist, and short GnRH agonist) in women with adenomyosis undergoing fresh embryo transfer. Only studies with ultrasound- or MRI-confirmed adenomyosis and extractable fresh-cycle outcomes were included. Implantation, clinical pregnancy, miscarriage, and live birth were analyzed. A frequentist random-effects network meta-analysis was performed using risk ratios and 95% confidence intervals, with SUCRA values used to rank protocol efficacy. Risk of bias was assessed using the Cochrane tool and ROBINS-I, and certainty of evidence was evaluated through CINeMA.

Seven retrospective studies were included. The ultra-long GnRH agonist protocol achieved the highest implantation rate and was significantly superior to the antagonist (RR 0.62; 95% CI 0.35–0.995) and short protocols (RR 0.53; 95% CI 0.31–0.83). No significant differences were observed for clinical pregnancy, miscarriage, or live birth, although Surface Under the Cumulative Ranking Curve (SUCRA) rankings consistently favoured the ultra-long regimen. In an exploratory subtype analysis, clinical pregnancy and live birth were comparable between focal and diffuse adenomyosis, whereas focal disease was associated with a lower miscarriage risk (RR 0.66; 95% CI 0.51–0.85).

The ultra-long GnRH agonist protocol appears to offer the most favorable reproductive outcomes for women with adenomyosis undergoing fresh embryo transfer, particularly for implantation and live birth probability. Focal adenomyosis is associated with lower miscarriage risk compared with diffuse disease, despite similar pregnancy and live birth rates. These findings support ultra-long down-regulation and routine subtype assessment, although confirmation in prospective trials is needed. Abbreviations - 2D/3D US: - Two-dimensional/three-dimensional ultrasound - CINeMA: - Confidence in network meta-analysis - CI: - Confidence interval - GnRH-a: - Gonadotropin-releasing hormone agonist - GnRH: - Gonadotropin-releasing hormone - IVF: - In vitro fertilization - ICSI: - Intracytoplasmic sperm injection - MRI: - Magnetic resonance imaging - NMA: - Network meta-analysis - PRISMA: - Preferred reporting items for systematic reviews and meta-analyses - PROSPERO: - International prospective register of systematic reviews - ROBINS-I: - Risk of bias in non-randomized studies of interventions - RR: - Risk ratio - SUCRA: - Surface under the cumulative ranking curve Funding Open access funding provided by University of Padjadjaran. This publication charge is funded by Unpad through the Indonesian Endowment Fund for Education (LPDP) on behalf of the Indonesian Ministry of Higher Education, Science and Technology and managed under the EQUITY Program (Contract No. 4303/ B3/DT.03.08/2025 and 3927/UN6. RKT/HK.07.00/2025) Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that there are no conflict of interest. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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/4.0/. About this article Cite this article Syam, H.H., Bayuaji, H., Tjahyadi, D. et al. Comparative efficacy of different IVF stimulation protocols in women with adenomyosis undergoing fresh embryo transfer: a systematic review and network meta-analysis. Arch Gynecol Obstet (2026). https://doi.org/10.1007/s00404-026-08557-2 Received: Accepted: Published: DOI: https://doi.org/10.1007/s00404-026-08557-2