Effect of Granulocyte Colony-Stimulating Factor on Clinical Pregnancy Outcomes of Recurrent Miscarriage and Recurrent Implantation Failure Cases: A Meta-Analysis

Objective: This meta-analysis aimed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the treatment of recurrent miscarriage (RM) and recurrent implantation failure (RIF). Methods: Eligible randomized controlled trials (RCTs) and cohort studies were retrieved from the Web of Science, Cochrane, and PubMed databases and evaluated using the Jadad scale or Newcastle-Ottawa Scale. Cochran's Q test and I2 statistics were used to assess heterogeneity. The effect sizes for clinical pregnancy and abortion rates of patients were pooled as risk ratios (RRs) and 95% confidence intervals (CI) using RevMan 5.3. Publication bias was assessed using funnel plots. Results: Thirteen studies (nine RCTs and three cohort studies) involving 1262 participants were included. Compared to the control/placebo group, the use of G-CSF significantly improved the clinical pregnancy rate [RRs (95% CI) = 1.73 (1.41, 2.12),p < 0.00001] of RIF patients; Whereas it had no significant impact on their abortion rate [RRs (95% CI) = 1.13 (0.43, 2.95),p = 0.80]. Both subcutaneous and intrauterine injections of G-CSF could improve the clinical pregnancy rate in RIF patients. However, subcutaneous injection showed a tendency to increase the abortion rate [RRs (95% CI) = 1.98 (0.40, 9.87), p = 0.40], whereas intrauterine injection showed a tendency to decrease the abortion rate for RIF patients [RRs (95% CI) = 0.93 (0.24, 3.53), p = 0.11]. In addition, G-CSF use had no significant impact on the clinical pregnancy rate of RIF patients in a South American study [RRs (95% CI) = 1.20 (0.60, 2.38),p = 0.60]. For RM patients, the use of G-CSF showed improved clinical pregnancy rates [RRs (95% CI) = 1.43 (0.76, 2.70), p = 0.27] and lower abortion rates [RRs (95% CI) = 0.80 (0.46, 1.14), p = 0.44] than control/placebo group; However, the difference was not significant. Similar results were observed in the subcutaneous, intrauterine injection, and regions subgroups of RM patients. Conclusions: This meta-analysis confirmed the benefits of G-CSF in improving the clinical pregnancy rate of RIF patients. No conclusive evidence supports the link between G-CSF use and increased abortion rate in RIF patients and clarifies the association of G-CSF use with clinical pregnancy and abortion rates in patients with RM.