Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion

Am J Reprod Immunol. 2014 May;71(5):458-66. doi: 10.1111/aji.12217. Epub 2014 Mar 10.

Abstract

Problem: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells).

Method of study: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation.

Results: By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001).

Conclusions: Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.

Keywords: IVIg therapy; natural killer cells; observational study; recurrent reproductive failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / drug therapy*
  • Abortion, Habitual / immunology
  • Abortion, Habitual / pathology
  • Adult
  • Female
  • Fertilization in Vitro
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Live Birth
  • Logistic Models
  • Lymphocyte Count
  • Natural Killer T-Cells / drug effects*
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / pathology
  • Pregnancy
  • Treatment Failure

Substances

  • Immunoglobulins, Intravenous
  • Immunologic Factors