Gonadotrophin dose in expected low responders undergoing ovarian stimulation for in-vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.

Introduction: Considering the prevalence and the importance of low ovarian response, it is important to update the evidence base on whether using higher compared to lower starting doses of gonadotrophins during ovarian stimulation of patients expected to exhibit low ovarian response is beneficial.

Evidence acquisition: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed by performing literature search until December 2024 in MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science and Clinicaltrials.gov. The primary outcome was live birth. Secondary outcomes included clinical and ongoing pregnancy, cumulative live birth, clinical and ongoing pregnancy, number of oocytes retrieved and number of usable embryos.

Evidence synthesis: Six eligible RCTs were identified (N.=2262). No significant difference was observed in live birth rates (RR: 0.96, 95% CI: 0.80-1.15; I²=0%, 2 studies, N.=1171), ongoing pregnancy rates (RR: 0.99, 95% CI: 0.81-1.19; I²=0%, 3 studies, N.=775), clinical pregnancy rates (RR: 1.04, 95% CI: 0.89-1.21; I²=0%, 5 studies, N.=1179) and the number of oocytes retrieved (WMD: -0.61, 95% CI: -2.52 to +1.31; I²=86.6%, 4 studies, N.=1286) between the groups compared. A lower number of usable embryos was observed (WMD: -0.38, 95% CI: -0.63 to -0.13; I²=0%, 3 studies, N.=1223) when using a lower compared to a higher starting dose of gonadotrophins in expected low responders undergoing ovarian stimulation for IVF/ICSI.

Conclusions: The available evidence is currently insufficient to conclude whether the use of a higher starting dose of gonadotrophins is beneficial in terms of live birth rates for patients expected to exhibit low response after ovarian stimulation.