There are patients in whom there may be an alteration of immunotolerance between the mother and the embryo, causing implantation failure and repeated miscarriages. Many studies have been carried out in this direction, although it is true that the conclusions are scarce and in most cases controversial.
Natural killer (NK) cells play an important role in implantation and may be related to infertility. This type of cell can be found both in peripheral blood and at the uterine level, with different characteristics and functions. In fact, uterine NK cells are considered essential for implantation because they have an immunoregulatory potential that peripheral blood NK cells do not have. Therefore, results derived from peripheral blood NK cell assessment should be interpreted with caution as they may not reflect what is happening at the uterine level. The association between NK cells and reproductive outcomes is one of the most controversial in assisted reproduction.
The prevalence of CD56+ NK cells in blood is approximately 10% of all peripheral blood lymphocytes. Some studies have reported that percentages as high as 12% may be related to poor reproductive outcomes.
Different treatments have been proposed over time. In 1980, paternal lymphocyte infusions were prescribed to these women, on the assumption that this treatment could stimulate a beneficial immune response to paternal antigens. This type of treatment was banned in 2002 by the FDA.
In the following years, different therapies have been tried including tumor necrosis factor-alpha (TNFa) inhibitors, intravenous immunoglobulins (IVIgI), intralipids, corticosteroids, or granulocyte colony-stimulating factors. However, great caution should be exercised when applying these treatments, as there is no clear evidence of their benefit and most of them carry significant health risks.
Therefore, it is essential that the treatment be prescribed and monitored by a specialist in reproductive immunology. Among the different options, corticosteroids would be the most widespread treatment given their immunomodulatory role and a profile with fewer associated risks than the other treatments.