The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis

Fertil Steril. 2018 Nov;110(6):1089-1100. doi: 10.1016/j.fertnstert.2018.07.004.


Objective: To study the current evidence on the role of immunotherapy in IVF and in the management of recurrent pregnancy loss (RPL).

Design: Systematic review and meta-analysis.

Setting: A literature search was performed using MEDLINE, PUBMED, CINAHL, and EMBASE until May 2017. Only randomized controlled trials were included, and a meta-analysis was carried out where appropriate.

Patient(s): Women undergoing IVF treatment with or without a history of recurrent implantation failure and women with idiopathic RPL.

Intervention(s): Assessment of the efficacy of commonly used immunomodulators such as IV use of [1] immunoglobulin, [2] lymphocyte immunotherapy and [3] intralipid; intrauterine infusion of [4] granulocyte colony-stimulating factor and [5] peripheral blood mononuclear cells; subcutaneous administration of [6] TNF-alpha inhibitors, [7] leukaemia inhibitory factor; and oral administration of [8] glucocorticoids.

Main outcome measure(s): The primary outcomes were live birth rate and miscarriage rate; secondary outcome was clinical pregnancy rate.

Result(s): Of the 7,226 publications identified, 53 were selected during the initial screening; 30 satisfied the selection criteria and were included in this review.

Conclusion(s): The available medical literature shows controversial results about the role of immunotherapy when used for improving reproductive outcomes. This study did not show a role for immunotherapy in improving the live birth rate in women undergoing IVF treatment or in the prevention of idiopathic RPL. Currently, immunotherapy should be used in the context of research and should not be used in routine clinical practice to improve reproductive outcomes.

Keywords: IVF; Immunotherapy; immunomodulation; recurrent pregnancy loss; repeated implantation failure.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abortion, Habitual / immunology*
  • Abortion, Habitual / prevention & control*
  • Birth Rate / trends
  • Female
  • Fertilization in Vitro / methods*
  • Fertilization in Vitro / trends
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Infertility, Female / immunology*
  • Infertility, Female / therapy*
  • Pregnancy
  • Pregnancy Rate / trends