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

Kayhan Yakin,Ozgur Oktem,Bulent Urman

doi:10.1038/s41598-019-40521-w

Abstract

It has been proposed that intrauterine administration of peripheral blood mononuclear cells (PBMCs) modulates maternal immune response through a cascade of cytokines, chemokines and growth factors to favor implantation. We conducted a meta-analysis to verify the effect of intrauterine PBMC administration on the outcome of embryo transfer in women with recurrent implantation failure (RIF). All relevant trials published in PubMed, Web of Science and Cochrane library databases were searched. Two randomized controlled trials and three cohort studies (1173 patients in total) matched the inclusion criteria. No differences in live birth rates were seen between the PBMC-treated patients and controls (OR: 1.65, 95% CI: 0.84–3.25; p = 0.14; I2: 66.3%). The clinical pregnancy rate was significantly higher in women who received intrauterine PBMCs before embryo transfer compared with those who did not (OR: 1.65, 95% CI: 1.30–2.10; p = 0.001, heterogeneity; I2: 60.6%). Subgroup analyses revealed a significant increase in clinical pregnancy rates with the administration of PBMCs in women with ≥3 previous failures compared with controls (OR: 2.69, 95% CI: 1.53–4.72; p = 0.001, I2: 38.3%). In summary, the data did not demonstrate an association between the administration of PBMCs into the uterine cavity before fresh or frozen-thawed embryo transfer and live birth rates in women with RIF. Whether intrauterine PBMC administration significantly changes live birth and miscarriage rates requires further investigation.

Highlights

During the last decade, particular interest has focused on the role of endocrine-immune interactions in the implantation process
In 2006, researchers reported that women with RIF who received intrauterine peripheral blood mononuclear cells (PBMCs) cultured with human chorionic gonadotropin experienced increases in implantation rates[4]
A significant improvement in the clinical pregnancy rate in women who had been given intrauterine PBMCs before embryo transfer was noted compared with those who had not (OR: 1.65, 95% confidence interval (CI): 1.30–2.10; p = 0.001, heterogeneity; I2: 60.6%)

Summary

Introduction

Particular interest has focused on the role of endocrine-immune interactions in the implantation process. The interplay between the invading embryo and mononuclear cells that come into contact with trophoblasts of embryonic origin through a cascade of cytokines, chemokines and growth factors actively occurs at the implantation site. Based on this rationale, it has been proposed that modulating the maternal www.nature.com/scientificreports/. In 2006, researchers reported that women with RIF who received intrauterine peripheral blood mononuclear cells (PBMCs) cultured with human chorionic gonadotropin (hCG) experienced increases in implantation rates[4]. The primary objective of this systematic review and meta-analysis was to assess the available evidence on the intrauterine administration of PBMCs in women with implantation failures, provide an estimate of the average treatment effect, and recommend how to improve the design of future trials

Methods

Results

Conclusion