Recombinant Human Granulocyte Colony-stimulating Factor for Reproductive Failure: A Systematic Review and...

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-stimu-lating factor (rhG-CSF) has been proposed as an immu-nomodulatory 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 significant-ly 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 re-ported. 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 out-comes in RIF, its effect on live birth remains uncertain. Fu-ture randomized trials should employ standardized treat-ment protocols and integrate immunogenetic diagnostics to optimize patient selection and clinical benefit.