Intrauterine administration of peripheral mononuclear cells in recurrent implantation failure: a systemic review and meta-analysis

Abstract

Objective: Is intrauterine administration of peripheral blood mononuclear cells (PBMC) associated with improved live birth rates (LBR) in women with recurrent implantation failures (RIF)? Design: A systematic review and meta-analysis of published clinical trials that studied women undergoing any form of ART (IVF, ICSI) who had intrauterine administration of PBMC with or without hCG culture before fresh or frozen embryo transfer. No adjuvant medical therapy should be given nor should asymmetric intervention be done in the control group. The primary outcome was the live birth rate and the secondary outcome parameters were the clinical pregnancy and miscarriage rates. Materials and Methods: Databases searched included MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials. Two randomized controlled trials and three cohort studies matched the inclusion criteria. Eligible studies were published between 2006 and 2017 and the sample sizes ranged from 35 to 663 patients. Odds ratio (OR) from individual studies were analysed using random effects models. Results: Live births were reported in four of the included studies (including 1119 patients). There was no difference in LBR between the PBMC treated and control groups (OR: 1.65, 95% CI: 0.84 - 3.25; p=0.14; heterogeneity; I 2 :66.3%). All five of the included studies (including 1173 patients) reported clinical pregnancy rates which were found to be improved in women who had been given intrauterine PBMC before embryo transfer compared to those who had not (OR: 1.65, 95% CI: 1.30- 2.10; p=0.001). Two studies (including 295 patients) reported miscarriages following treatment, showing comparable rates in women treated with PBMC and controls (OR: 0.21, 95% CI: 0.02 - 2.43; p=0.21). Cochrane’s and ROBINS-I tools were used to assess the quality of the included studies, suggesting low to moderate risk of bias. Conclusions: Circulating mononuclear cells might be playing a critical role in the immune modulation of intrauterine environment favouring pregnancy. However, the current data shows that administration of PBMC with or without hCG culture into the uterine cavity before fresh or frozen-thawed embryo transfer does not improve LBR in women with RIF. A well designed randomized controlled trial with an optimal sample size should be considered to investigate the benefits of intrauterine PBMC administration.