Do natural killer cells (NK cells) affect fertility?

Link between NK cells and implantation of embryos may be overblown

Natural killer (NK) cells are an important subgroup of lymphocytes (a subgroup of white blood cells) which have a large variety of functions, from killing cancer cells to, potentially, also killing the “invading” (i.e., implanting) embryo if the immune system sees the embryo as “foreign.”

Because half of the embryo is paternal, it is not surprising that a maternal immune system would see an implanting embryo as “foreign” – as it would see an organ transplant from the partner – and attack it. Yet, if a woman has a normally functioning immune system, such an attack does not happen because her immune system, in response to messages from the embryo, reprograms itself from rejection to tolerance of the embryo. Women who have hyper-active immune systems due to autoimmunity, inflammation or even from being very hyper-allergenic, do not reprogram their immune systems appropriately. As a consequence, their immune systems still view embryos as “foreign,” attack them, thereby causing implantation failure and/or pregnancy loss.

Research suggests that NK cells play a very important role in developing this tolerance, but further details are still quite iffy because local endometrial NK cells are functionally very different from peripheral NK cells that are measured in a blood test. To conclude from peripheral NK cell counts that a patient may have an implantation problem, therefore, appears quite far-fetched.

Consequently, CHR does not use NK cell counts as a diagnostic test for either implantation failure or increased miscarriage risk. Instead, CHR searches for broad evidence of a hyper-active maternal immune system by testing patients’ bloods for autoimmune markers, inflammatory markers and evidence for a hyper-allergenic state. If such evidence is discovered (and the literature suggests that the prevalence of hyperactive immune systems is much higher in infertile women than in the general population), an assumption is reached that such a patient is likely at risk to develop inadequate maternal tolerance and, therefore, to experience an allogeneic maternal immune response against the fetus, potentially leading to implantation failure and/or miscarriages. Maternal treatment then must be directed at calming down this allogeneic immune response.

This is a part of the September 2018 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.