The effectiveness of immunotherapies for patients with repeated implantation failure: a systematic review and network meta-analysis

Background: This study compared clinical pregnancy outcomes of repeated implantation failure (RIF) patients treated with immunotherapies using a network meta-analysis.Methods: Publications are determined by searching the Pubmed, Embase and web of science databases. The search date is from the establishment of the database till August 2021. The outcomes were clinical pregnancy rate (CPR), live birth rate (LBR) and implantation rate (IR). The Cochrane bias risk assessment tool was applied to evaluate the quality of the study, and Stata 14.0 was used for the network meta-analysis.Results: A total of 16 RCTs including 2008 participants were included. The network meta-analysis results show that PBMC, PRP and SC-GCSF can significantly improve CPR compared with LMWH (PBMC: OR = 2.15; 95% CI, 1.21-3.83; PRP: OR = 2.38; 95% CI, 1.08-5.24; SC-GCSF: OR = 2.46; 95% CI, 1.05-5.72). The LBR of PRP was significantly higher than IU-GCSF (OR = 3.81; 95% CI, 1.22-11.86), LMWH (OR = 4.38; 95% CI, 1.50-12.90) and Intralipid (OR = 3.85; 95% CI, 1.03-14.29), and the LBR of PBMC was also significantly better than that of LMWH (OR = 2.35; 95% CI, 1.14-4.85). Furthermore, PRP treatment significantly improved IR compared with LMWH treatment (OR = 2.81; 95% CI, 1.07-7.4).Discussion: Based on the limited evidence from existing RCTs, PBMC and PRP seem to be the best therapeutic options for RIF patients. However, due to research quantity restrictions, more top-quality researches are required in the future to obtain additional high-level evidence.