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

This meta-analysis analyzed the clinical pregnancy outcomes of repeated implantation failure (RIF) patients treated with immunomodulatory therapies. Publications (published by August 16, 2021) were identified by searching the PubMed, Embase, and Web of Science databases. The quality of the studies was evaluated with the Cochrane bias risk assessment tool, and a network meta-analysis was performed with Stata 14.0. The outcomes were clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). The results of our network meta-analysis of 16 RCTs (including 2,008 participants) show that PBMCs, PRP, and SC-GCSF can significantly improve the CPR compared with LMWH (PBMCs: 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 those of 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 PBMCs was also significantly better than that of LMWH (OR 2.35; 95% CI 1.14–4.85). Furthermore, PRP treatment significantly improved the IR compared with LMWH treatment (OR 2.81; 95% CI 1.07–7.4). The limited evidence from existing RCTs suggests that PBMCs and PRP are the best therapeutic options for RIF patients. However, owing to the quantity limitation, more top-quality research is required to obtain additional high-level evidence.