Natural Killer Cell Testing
Implantation failure and early pregnancy loss are common and are particularly distressing problems to overcome in assisted reproduction. The exact underlying causes for recurrent implantation failures following IVF and pregnancy losses is not clear. Out of the factors considered to play a significant role are immunological disorders. One of the most common immunological causes for reproductive failure is suggested to be elevated level of Natural Killer (NK) cell activity.
Natural killer cells are a type of lymphocyte (a white blood cell) and an important part of the body’s defence mechanisms. They can be seen as the soldiers of the immune system where they play a major role in defending against invading foreign bodies, tumours and infected cells. Genetic studies indicate that Natural Killer (NK) cells regulate the survival of the embryo and fetus. They also contribute to the development and the invasion of the placenta.
The question of whether elevated NK cell levels are a cause of infertility and pregnancy loss, and whether they provide a potential target for therapy to improve reproductive outcomes, lacks a definitive answer. It is clear, however, that a significant number of women with reproductive failure have abnormal NK cell numbers suggesting high immunological activity.
The hypothesis is that in some women, a hyperactive immune system within the uterine cavity (inside the womb), may be present. This, in turn, may reduce the rate of embryo survival or hamper a successful placentation (growth of the placenta) to feed the fetus leading to recurrent implantation failures in IVF treatments or recurrent miscarriages.
What to do
If this hypothesis is correct, temporarily supressing the NK cell numbers prior to the transfer of an embryo should improve the chances of a successful implantation. Although there is still uncertainty over the precise pathophysiological basis for all immune investigations and therapy, this should not be a barrier for clinical observation and empirical care.
Instead of applying treatments to manipulate NK cell levels blindly, we recommend an investigation based-approach. An endometrial biopsy (sample taken from the lining of the womb) during the implantation window (when an embryo normally implants, which is usually day 19-21 of your cycle) would be the best representative of the environment for your embryo. A sample is taken from the lining of the womb in a cycle prior to your IVF treatment. This sample is then tested to check its NK cell content. If the numbers of NK cells are raised, depending on the levels, appropriate treatment can be prescribed and the dose of medication adjusted precisely.
Treatment
Immunotherapy for treatment of reproductive failure appears to enhance live births in those women displaying immunologic risk factors such as raised NK cell numbers in the endometrium. A number of treatments have been suggested and tried to manipulate the endometrial immune environment and the NK cell numbers. The most successful treatments so far have been;
- Intravenous immunoglobulin (IVIg)
- Intralipid
Intravenous immunoglobulin therapy (IVIg) has been successful in the treatment of recurrent miscarriage and recurrent implantation failure among women with elevated NK Cell activity.
Intravenous administration of intralipids also improves the rate of live births. When the pregnancy outcomes of women with a history of recurrent reproductive failure and elevated NK cell numbers treated with intralipid infusion were compared with women treated with IVIg, no differences were seen. However IVIg is a blood product and it is very expensive. In laboratory tests, its effectiveness appears to be equal to intralipid in suppressing NK cell cytotoxicity.
Therefore, it appears that both intralipids and IVIg act as immunomodulators and can be used clinically in modulating the NK cell activity; although when the pregnancy outcomes treated with IVIgs and intralipids were compared the results were similar