Treatment of G-CSF in unexplained, repeated implantation failure: A systematic review and meta-analysis

Backgroud: Repeated implantation failure (RIF) is a stressful situation for subfertile women undergoing in vitro fertilisation (IVF) treatment and caregivers. Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in assisted reproductive techniques. However, it is currently unknown whether G-CSF is effective in improving results for patients with RIF. Objective: To describe and summarize current evidence of the effect of the granulocyte colony stimulating factor (G-CSF) in treating RIF. Method: Relevant scientific literature was thoroughly searched by computer in domestic and foreign database from the inceptions to November 2019. And relevant randomized controlled trials (RCTs) assessing the efficacy of G-CSF in unexplained RIF were included. The meta-analysis was conducted by Stata 12. 0 software, and we estimated relative risks (RRs) and associated 95 % confidence intervals (Cis) of G-CSF on implantation rate (IR), the clinical pregnancy rate (CPR), the abortion rate (AR) in patients with unexplained RIF using fixed-effect model. Besides, Subgroup analysis was performed according to the different administration methods. Result: A total of eleven articles were included for the final meta-analysis with sample sizes ranging from 13 to 107 patients. The G-CSF was associated with an increased IR [RR = 2.346, 95 %CI (1.615-3.409), I-2 = 0. 0%] and CPR [RR = 1.910, 95 %Cl (1.562-2.337), I-2 = 0.0 %] in patients with unexplained RIF. When further stratified by the method of administration, the subgroup analysis revealed that both intrauterine injection and subcutaneous injection are capable of improving IR[subcutaneous injection:RR = 2.400, 95 %CI (1. 268-4. 542), I-2 = 0.0 %; intrauterine injection:RR = 2.317, 95 %CI (1.462-3.673), I-2 = 0.0 %] and CPR [subcutaneous injection: RR = 2.022, 95 %CI (1.443-2.832), I-2 = 0.0%; intrauterine injeciton: RR = 1.848, 95 %CI (1.438-2.376), I-2 = 0.0%]. G-CSF was not associated with AR in patients with unexplained RIF [RR = 2.092, 95 %Cl (0.815-5.369), I-2 = 0.0 %]. Conclusion: The current evidence support G-CSF's positive effect on the implantation rate and clinical pregnancy rate of patients with unexplained RIF, especially when administrated by subcutaneous injection. There is no conclusive evidence for the association between G-CSF and the abortion rate. Moreover, few of the included articles reported side effects of G-CSF, so its safety remains to be investigated. Thus, future research should evaluate. (C) 2020 Elsevier Masson SAS. All rights reserved.