Immunology and human reproduction

The immune system's role in recurrent reproductive failure is a controversial issue in assisted reproduction. New insight about maternal tolerance in assisted reproduction has been reported and could explain some of the recurrent miscarriage and/or recurrent implantation failure related causes named until now as unknown.

Most of the previous studies about immune system implication in reproduction were focused on finding markers on peripheral blood. Maternal 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 cells and their ligand human leukocyte antigen (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 review provides insight about the immune tolerance process. 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 miscarriage or recurrent implantation failure and a KIR AA haplotype.