The Immune System & Infertility – Victory ART Laboratory

The role of the immune system in pregnancy has been both agonistic and antagonistic in nature. Many health professionals feel that an active immune system can potentially cause damage to the placenta, resulting in miscarriage. For example, natural killer (NK) cells, which have beneficial anti-cancer properties, can proliferate within the uterus and do damage.

If you have a family history, medical history, or even suspicion of immunological disorders, there are several tests that can be conducted to check different aspects of your immune system. These include the following tests:

1. Natural Killer (NK) Cell Cytoxicity Assay and Immunophenotype:
This test measuresthe effectiveness (i.e. killing power) of NK cells in a sample of blood. If this is elevated, then it may be associated with failed implantation as well as spontaneous abortion. Specific types of cells are associated with fertility problems, especially CD56+ NK cells, and CD19+5+ B cells, the latter of which is associated with the production of autoimmune antibodies.

2. TH1:TH2 Cytokine ratio
Cytokines,or chemical messengers,are protein complexes that circulate in the bloodstream. High levels of the TH1 pro-inflammatory cytokine, TNF-alpha, are frequently associated with reduced egg quality, implantation failure and miscarriage. By measuring this ratio of TNF-alpha in the blood compared to the anti-inflammatory cytokine, interleukin 10 (IL-10) as well as the ratio of Interferon-gamma compared to IL-10, the imbalance of these cytokines can be identified.

3. Leukocyte Antibody Detection (LAD)
This test requires a sample of blood from both the prospective mother (or gestational carrier) and the prospective father. As a cross-matching test,the interaction between blocking antibodies in the mother’s blood and samples of white blood cells from the prospective father are observed. Low levels of blocking antibodies are correlated with increased rates of implantation failure.

4. HLA-DQ Alpha Testing
This test identifies which DQ-alpha markers are carried within the body. If both prospective parents carry similar markers, miscarriage ratesare increased. This test is usually conducted on both parents. Once this has been established, Lymphocyte Immune Therapy (LIT) can be initiated to build up adequate levels of blocking antibodies.

5. Uterine Biopsy
A small tissue sample is taken from the lining of the uterus, ideally before menstruation. Samples are analyzed for abnormally high levels of uterine NK cells, levels of FoxP3+ T-regulatory cells and for the health and development of the uterine lining.

6.Tests for inherited thrombophaelia:
All thrombophaelia (‘sticky blood conditions’) are genetic conditions that can cause problems for maintaining an adequate blood supply to the uterine lining and to the growing placenta. This results in increased rates of implantation failure and miscarriage.

7. Screening for Autoimmune Factors
Undiagnosed autoimmune disease may be associated with increased risk of pregnancy failure, potentially due to elevated TNF-alpha ratios. A screening panel will commonly include tests for Antinuclear Antibodies (ANA), Anti-Histone and ds-DNA antibodies. These tests are commonly available at internal medicine and GP clinics.

8. Killer-Cell Immunoglobulin-like Receptors (KIRs)
KIRs are a category of protein receptors on the surface of NK cells, some of which are activating in nature. There is an increased risk of implantation failure or miscarriage if specific members of the activating KIRs are missing. Treatment includes supportive immune therapy, such asintralipids or IVIg infusions, corticosteroids, progesterone and Lymphocyte Immune Therapy (LIT).