Archives of Gynecology and Obstetrics

, Volume 300, Issue 5, pp 1445–1459 | Cite as

Autologous peripheral blood mononuclear cells intrauterine instillation to improve pregnancy outcomes after recurrent implantation failure: a systematic review and meta-analysis

  • Yang Wu
  • Lifei Li
  • Lin Liu
  • Xia Yang
  • Peijing Yan
  • Kehu Yang
  • Xuehong ZhangEmail author
Gynecologic Endocrinology and Reproductive Medicine



Recurrent implantation failure (RIF) is a common cause of disappointment and a big challenge after assisted reproduction technology treatments. The objective of this study was to evaluate the existing literature to explore whether peripheral blood mononuclear cells’ (PBMCs) instillation could improve pregnancy outcomes among patients with RIF.


We conducted a comprehensive search including PubMed, EMBASE, Cochrane library and various databases in China. Three randomized controlled trials (RCTs) and three non-randomized controlled trials (non-RCTs) were included. We included subgroup and sensitivity analyses using Stata 12.0.


The results of the three RCTs showed that PBMC improved outcomes in all patients compared with placebo or no-treatment [clinical pregnancy rate (CPR): odds ratio (OR) 2.45, 95% confidence interval (CI) 1.53–3.91; implantation rate (IR): OR 2.46, 95% CI 1.48–4.09; live birth rate (LBR): OR 2.43, 95% CI 1.32–4.49]. However, the results of the three non-RCTs indicated that there were no statistically significant differences in the outcomes and that the heterogeneity was higher (I2 > 0%). Subgroup analysis further suggested that PBMCs treatment significantly increased the CPR, IR and LBR in the three or more implantation failure subgroups (CPR: OR 2.83, 95% CI 1.29–6.22; IR: OR 3.74, 95% CI 1.71–8.19; LBR: OR 3.03, 95% CI 1.15–7.98).


Among patients with three or more implantation failures, this treatment improved IR, LBR, and CPR compared to that in controls, due to the limited data available, PBMCs’ intrauterine instillation should only be used in the context of clinical trials.


Recurrent implantation failure Peripheral blood mononuclear cell In vitro fertilization Assisted reproductive technology 



There was no funding received for the creation and completion of this work.

Author contributions

YW, LFL, and XHZ conceived and designed the study. YW, LFL, and XY analysed the data. YW and LL wrote the “Introduction and Discussion”. YW and PJY wrote the “Materials and methods” and “Results”. KHY and XHZ provided significant advice for the manuscript. YW and XY were primarily responsible for writing and modifying the draft.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.First Clinical Medical College of LanZhou UniversityLanzhouPeople’s Republic of China
  2. 2.The Reproductive Medicine Special Hospital of the 1st Hospital of Lanzhou UniversityLanzhouPeople’s Republic of China
  3. 3.Key Laboratory for Reproductive Medicine and Embryo of GansuLanzhouPeople’s Republic of China
  4. 4.Institution of Clinical Research and Evidence Based MedicineGansu Provincial HospitalLanzhouPeople’s Republic of China
  5. 5.Evidence-Based Medicine Center, School of Basic Medical ScienceLanzhou UniversityLanzhouPeople’s Republic of China

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