Abstract
Reproductive failure including recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF)—is often attributed to immune dysregulation at the maternal–fetal interface. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been proposed as an immunomodulatory therapy to enhance reproductive outcomes. This systematic review and meta-analysis included 10 randomized controlled trials evaluating rhG-CSF in women diagnosed with RPL or RIF. The primary outcomes were clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). Overall, rhG-CSF did not significantly improve CPR (odds ratio [OR]=1.16; 95% confidence interval [95% CI], 0.48–2.80; p=0.74) and showed high heterogeneity (I²=86%). Subgroup analysis indicated a significant increase in CPR among RIF patients (OR=1.73; 95% CI, 1.17–2.55; p=0.006; I²=17%), while no benefit was observed in RPL. No significant differences were found for LBR (OR=1.53; 95% CI, 0.88–2.66; p=0.13) or MR (OR=0.72; 95% CI, 0.26–1.96; p=0.52). Safety profiles and obstetric or perinatal outcomes were inadequately reported. The high heterogeneity likely reflects variation in patient selection, rhG-CSF dosing regimens, and the lack of immunological stratification for identifying responsive subgroups. While rhG-CSF may improve implantation outcomes in RIF, its effect on live birth remains uncertain. Future randomized trials should employ standardized treatment protocols and integrate immunogenetic diagnostics to optimize patient selection and clinical benefit.