Immune Factors in Recurrent Implantation Failure

  • Diana Alecsandru
  • Juan A. Garcia-Velasco


The immune system’s role in recurrent reproductive failure is a controversial issue in assisted reproduction. Most of the previous studies about immune system implication in reproduction were focused on finding markers on peripheral blood and less on uterine environment. Maternofetal tolerance begins at the uterine level, so successful adaptation to the fetus happens after a complicated process. Insufficient invasion of the uterine lining by invading extravillous trophoblast is the primary defect in pregnancy disorders such as recurrent miscarriage, and this process is regulated by interaction between maternal killer immunoglobulin-like receptors (KIRs) expressed by the uterine natural killer (uNK) cells and their ligand human leukocyte antigen-C (HLA-C) expressed by extravillous trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR AA when the fetus has paternal HLA-C2. Recently, it has been reported that the expression of more than one paternal HLA-C by extravillous trophoblast in assisted reproduction may affect placentation in mothers with KIR AA.

The chapter provides insight about the immune tolerance process and the role of the uterine NK cells on this complex process and RIF. These insights could have an impact on the selection of single embryo transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent implantation failure and recurrent miscarriage by their KIR haplotype.


Human leukocyte antigen-C (HLA-C) Killer immunoglobulin-like receptor (KIR) Maternofetal immune tolerance Uterine natural killer cells 



Assisted reproductive treatments


Double embryo transfer


Invading extravillous trophoblast


Human leukocyte antigen


In vitro fertilization


Killer immunoglobulin-like receptor

NK cells

Natural killer cells


Peripheral blood


Recurrent implantation failure


Recurrent miscarriage


Single embryo transfer

uNK cells

Uterine natural killer cells


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Rey Juan Carlos University, IVI RMA-MadridMadridSpain

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