Prednisone improves pregnancy outcome in repeated implantation failure by enhance regulatory T cells bias

J Reprod Immunol. 2021 Feb:143:103245. doi: 10.1016/j.jri.2020.103245. Epub 2020 Nov 2.

Abstract

Objective: Repeated implantation failure (RIF) has been shown related to maternal immune imbalance. Many studies suggested that prednisone promoted the Th17/Treg balance shift to the direction of immune tolerance. Our study aimed to evaluate the role of prednisone in Th17/Treg balance and pregnancy outcome in RIF patients.

Study design and main outcome measures: Peripheral blood of healthy fertile controls and RIF patients were collected at the late proliferation phase. The population of Treg and Th17 cells, the expression of Foxp3 and RORC mRNA and the concentration of IL-17A, IL-23 and IL-10 were detected by flow cytometry, qRT-PCR and enzyme-linked immunosorbent assay. RIF patients were given oral prednisone 10 mg daily from the late proliferation phase of the cycle before FET. After one month of treatment, the above immune indicators were tested, and natural cycle frozen embryo transfer was performed.

Results: The Treg cells proportion and IL-10 concentration in peripheral blood of RIF patients was lower than that of NF group, while the proportion of Th17 cells and concentration of proinflammatory cytokine were significantly higher. After prednisone treatment, the indicators related to immune tolerance increased significantly. Five out of 19 RIF patients were successful pregnancy after FET, in which, one had an early miscarriage and four live births. No pregnancy complications and fetal abnormalities were observed.

Conclusions: We report the beneficial effect of prednisone on RIF patients. The underlying mechanism may attribute to shift the Treg/Th17 immune balance to a Treg bias, and enhance embryo implantation, ultimately improve pregnancy outcomes.

Keywords: Immune tolerance; Prednisone; Regulatory T cells; Repeated implantation failure; T helper 17 cells.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Case-Control Studies
  • Embryo Implantation / drug effects*
  • Embryo Implantation / immunology
  • Embryo Transfer / statistics & numerical data
  • Female
  • Fertilization in Vitro / methods*
  • Fertilization in Vitro / statistics & numerical data
  • Healthy Volunteers
  • Humans
  • Immune Tolerance / drug effects
  • Infertility, Female / blood
  • Infertility, Female / immunology
  • Infertility, Female / therapy*
  • Interleukin-10 / blood
  • Interleukin-10 / metabolism
  • Live Birth
  • Prednisone / administration & dosage*
  • Pregnancy
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Treatment Outcome

Substances

  • IL10 protein, human
  • Interleukin-10
  • Prednisone