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

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.

To describe and summarize current evidence of the effect of the granulocyte colony stimulating factor (G-CSF) in treating RIF.

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.

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), I² = 0. 0%] and CPR [RR = 1.910, 95 %CI (1.562-2.337), I² = 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), I² = 0.0 %; intrauterine injection:RR = 2.317, 95 %CI (1.462-3.673), I² = 0.0 %] and CPR[subcutaneous injection: RR = 2. 022, 95 %CI (1.443-2.832), I² = 0. 0%; intrauterine injeciton: RR = 1.848, 95 %CI (1.438-2.376), I² = 0. 0%]. G-CSF was not associated with AR in patients with unexplained RIF [RR = 2.092, 95 %CI (0.815-5.369), I² = 0.0 %].

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.