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

Abstract 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. Objective 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. Methods 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. Results 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). Conclusions 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.