Repeated miscarriages in early pregnancy and problems with fetal delivery have different causes. One of them may be an incompatibility between the immune system of the mother's uterus and the genotype of the embryo, which can only be identified by special testing. On the basis of its results, experts can assess what the immunological reaction of the mother to the embryo may be. This is one of the key factors that determine the success of the embryo's nesting and further development. Any intolerance of the embryo's genotype can result in serious complications during pregnancy, often leading to miscarriage and abortion. The method is intended primarily for couples whose hopes for a child have been thwarted by repeated abortions in the past.

The success of the pregnancy can be determined by immunogenetics

Depending on their genotype, each person carries a specific combination of HLA-C antigens that can significantly affect the reproductive process. At the same time, they carry a unique set of so-called KIR receptors, which represent one of the key elements of our innate immunity. These receptors play an important role not only in the body's normal immune reactions, for example to infection, but also in the transplantation of donated organs or even embryos, where the body depends on them for acceptance. "The human immune system is ready to eliminate anything it recognises as foreign. This can also happen during the pregnancy when the mother's immune system reacts with the embryo, which has antigens from the father in addition to the mother's antigens. "The mother's tolerance or intolerance to the combination of HLA-C antigens in the embryo is determined by her immune cells and their KIR receptors responsible for natural immunity in the mother's uterus. The success of the pregnancy also depends on their compatibility."

Incompatibility puts both fetus and mother at risk

Extensive research studies confirm that in the case of couples whose efforts to have a child have ended in repeated miscarriages, one of the reasons may be the immunological intolerance of the uterus towards the embryo. This means that even if both partners are healthy and fertile, their immunological incompatibility can ultimately lead to spontaneous abortions. HLA+ testing can answer the search for the causes of recurrent problems with fetal delivery by assessing the compatibility between the KIR receptors in the uterus and the HLA-C antigens of the embryo. "Some KIR receptors in the mother's uterus may show a high degree of intolerance to certain subtypes of HLA-C antigens. This is to the extent that a woman may become pregnant but repeatedly lose the fetus. Another very serious consequence of such incompatibility is preeclampsia, which can fatally endanger the development and life of the fetus and the mother herself," explains MUDr. Višňová. 

For whom HLA+ testing is suitable

The HLA+ test was made available to patients by the IVF clinic CUBE as the first and so far the only one in the Czech Republic. It is not an experimental method, it has been successfully used abroad for several years. The test is indicated mainly for couples who have conceived a child naturally or undergone IVF treatment with their own or donated eggs. Still, the pregnancy repeatedly ended in spontaneous abortion of the fetus. The HLA+ test can also reveal the cause of problems with fetal delivery. "If the KIR receptors of the uterus are shown to have a high level of intolerance to the combination of HLA-C antigens that the embryo would have acquired from its own egg and the partner's sperm, the couple may be recommended IVF therapy using a donor program. In this case, HLA+ testing will also allow us to select the donor who is most compatible with the KIR receptors of the patient's uterus in terms of the HLA-C antigen combination. This will significantly increase the chances of success of IVF therapy and pregnancy," adds MUDr. Višňová.

HLA+ testing is performed on a sample of the couple's blood. In the case of IVF therapy with donated cells, the potential donor's blood is also tested. The method is currently not covered by health insurance.

Explanatory notes:

HLA-C (Human Leucocyte Antigen-C) - a large complex of genes that determine surface molecules (antigens) located in the plasma membrane of cells. It is the major histocompatibility system that is primarily responsible for distinguishing self from foreign.

KIR (Killer Immunoglobulin Receptors) - transmembrane glycoproteins found on the surface of human NK (Natural Killer Cell) cells of the immune system. These receptors interact with MHC I molecules found on the surface of most body cell types to regulate the cytotoxic functions of NK cells. KIR receptors are able to distinguish healthy cells from e.g. tumour or virus-infected cells.