Abstract Background Patients with diminished ovarian reserve (DOR) present a significant challenge in assisted reproductive technology due to their poor ovarian response and lower pregnancy rates. Although multiple ovarian stimulation protocols are available, the optimal regimen for DOR patients remains uncertain, largely due to population heterogeneity and inconsistent outcome reporting. Purpose To compare the efficacy of five commonly used controlled ovarian stimulation protocols, including GnRH agonist, GnRH antagonist, mild stimulation, progestin-primed ovarian stimulation (PPOS), and double ovarian stimulation (DOS), in patients with DOR, using a network meta-analysis stratified by Bologna and POSEIDON criteria. Methods This was a systematic review and network meta-analysis including randomized controlled trials and retrospective cohort studies identified through searches of PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2024. The analysis involved studies comparing various controlled ovarian hyperstimulation (COH) regimens in DOR patients. The included studies enrolled women diagnosed with DOR based on Bologna or POSEIDON criteria. The primary outcome was live birth rate at the first embryo transfer (ET) cycle, while secondary outcomes included the number of oocytes retrieved, clinical pregnancy rate at first ET, cumulative live birth rate, and cycle cancellation rate. Network meta-analyses were performed using STATA V.14.0 and R V.4.3.2 to compare outcomes across different stimulation protocols within stratified patient groups. Results In the Bologna group, the double ovarian stimulation (DOS) protocol demonstrated significantly higher effectiveness in terms of live birth rates. Additionally, it yielded higher oocyte counts and clinical pregnancy rates, while also resulting in lower cycle cancellation rates. However, under the POSEIDON criteria, the results varied. For patients categorized in POSEIDON group 3, the GnRH agonist protocol achieved the highest live birth rate, significantly outperforming mild stimulation (OR 7.69, 95% CI: 3.57–16.67) and GnRH antagonist (OR 1.97, 95% CI: 1.36–2.85). The GnRH agonist protocol also led in oocyte retrieval, cumulative live birth rate, and clinical pregnancy rate, and showed a lower cycle cancellation risk. In contrast, for POSEIDON group 4 patients, no significant differences in live birth rates, clinical pregnancy rates or cycle cancellation risk were observed among protocols. While DOS resulted in higher oocyte retrieval than other protocols, GnRH agonist showed a higher cumulative live birth rate than GnRH antagonist (OR 1.25, 95% CI: 1.04–1.50). Conclusions This analysis highlights the importance of individualized stimulation protocols based on patient stratification. For DOR patients, especially those classified using POSEIDON criteria, tailoring ovarian stimulation strategies could enhance clinical outcomes. Future prospective trials are warranted to refine protocol recommendations for specific DOR subgroups.
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