Background: Response to ovarian stimulation varies among patients. Low ovarian responders (LORs) represent a particularly challenging subgroup, and numerous strategies have been explored to improve their outcomes. Dual stimulation has emerged as a potentially promising approach to increase the number of retrieved oocytes, mature oocytes, and consequently, the number of available embryos and the likelihood of achieving a live birth in this population. However, current evidence regarding the efficacy of dual stimulation in LORs remains limited, warranting further high-quality studies. Objective: This systematic review and meta-analysis aimed to compare live birth rates between dual ovarian stimulation and single or two conventional stimulation cycles in LORs undergoing ART. Materials and Methods: A systematic review and meta-analysis was performed comparing dual ovarian stimulation (two stimulation phases separated by 50%), results were combined with the intention-to-treat (ITT) principle supplementary per protocol (PP) analyses were performed and are reported as relative risk (RR) or weighted-mean-difference (WMD) with 95% confidence intervals (CI). Subgroup analysis was performed based on whether dual ovarian stimulation was compared with one or two consecutive conventional stimulation cycles. Main outcomes: Six RCTs (n=428) were identified. Two studies were excluded from the meta-analysis because of low trustworthiness. No significant difference was observed in live birth (RR: 0.78, 95% CI: 0.48-1.26; I2=22.7%, three studies, n=216), ongoing pregnancy (RR: 1.08, 95% CI: 0.54-2.18; I2 =0%, one study, n=120), clinical pregnancy (RR: 0.90, 95% CI: 0.43-1.88; I2=69.8%, three studies, n=256) and miscarriage (RR: 1.24, 95% CI: 0.50-3.08; I2=21.4%, four studies, n=336). The subgroup analyses suggested a significant difference between the two subgroups (p=0.04) in clinical pregnancy rates: dual ovarian stimulation versus single conventional stimulation (RR: 1.21, 95% CI: 0.68-2.17) and dual ovarian stimulation versus two consecutive conventional cycles (RR: 0.44, 95% CI: 0.20-0.96). One study (n=80) reported significantly fewer total oocytes (WMD: -4.20; 95% CI: -5.22 to -3.18), MII oocytes (WMD: -1.90; 95% CI: -2.67 to -1.13), and available embryos (WMD: -0.60; 95% CI: -0.84 to -0.36) in the dual stimulation group. Conversely, PP analysis, including three studies (n=233), did not identify any significant differences between groups in the number of oocytes, MII oocytes, and available embryos.
Κωνσταντίνα Κ. Τσιούλου (Wed,) studied this question.