Immune Testing For Infertility


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There is currently much ongoing debate going on in the scientific community about the role of the immune system in promoting or preventing a healthy pregnancy. There is a view pioneered by late Dr Alan Beer that the products of an activated immune system could damage the placenta and cause miscarriage, as well as damage the embryo and cause implantation failure. Natural killer cells, which help to keep the body from developing cancer, can over-populate the uterus or exist at too high levels within the blood stream. These cells then go overboard, killing the embryo or interfering with the endocrine system that produces the hormones that are essential for pregnancy.

At The Fertility & Gynaecology Academy we carry out a comprehensive group of tests to check different aspects of your immune system and related clotting factors (thrombophilia) to enable a successful IVF treatment.

These include the following tests:

Natural Killer (NK) cell cytoxicity assay and Immunophenotype

This test is a measure of the killing power of the NK cells in your blood. Elevated killing power is often associated with failed embryo implantation and miscarriage.

Additionally, we measure how much reduction in NK killing power is observed in the laboratory after adding a solution of medication (IVIg or Intralipids) to a sample of NK cells from your blood.

The second part of the test measures the numbers of various types of white cells in your blood as percentage of the whole. We look at these specific types of cells because elevated concentrations of these cells have been shown to be associated with various fertility problems. For example:

  • CD56+ Natural Killer cells
  • CD19+5+ B cells associated with auto-immune antibody production.

TH1:TH2 Cytokine ratio

Cytokines are chemical messengers in the blood. High levels of the TH1 pro-inflammatory cytokine, TNF-alpha, in particular, have been shown to be associated with reduced egg quality, implantation failure and miscarriage.

This test measures the ratio of TNF-alpha in your blood compared to the anti-inflammatory cytokine, IL10. We also measure the ratio of Interferon-gamma compared to IL10.

Leukocyte Antibody Detection (LAD)

This is a “Crossmatch test” which measures the levels of blocking antibodies in the prospective mother’s blood to samples of white cells from the prospective father. This test requires a sample of blood from both the prospective mother (or gestational carrier) and the prospective father. Low levels of blocking antibodies are associated with higher rates of miscarriage and implantation failure. If you have no available partner you can have the test against any other person’s blood.

HLA-DQ Alpha testing

This test determines which DQ Alpha markers your body cells carry. Where the prospective mother and father carry very similar markers, there is an increased chance that their embryos may carry identical markers to the mother. In that case, there may be an increased rate of implantation failure and/or miscarriage due to an increased immune response which may become more aggressive with each successive attempted implantation of a DQ Alpha matching embryo. To be informative, this test is usually done for both the prospective mother and the prospective father. If a couple of matching DQa genes need Lymphocyte Immune Therapy (LIT) one of the two LIT injections should be from a donor who has at least one different DQa from the prospective mother to build up adequate levels of blocking antibodies.

Testing by uterine biopsy

This test requires a small sample taken from the lining of the uterus, ideally before your period is due. The sample can be taken at our clinic or, in some cases, taken elsewhere and forwarded to us. Samples are analysed for excessive levels of uterine NK cells, for adequate levels of FoxP3 +ve T-regulatory cells and for the health and development of the uterine lining.

Tests for inherited thrombophilia: Factor II & V, MTHFR gene mutation etc.

These are genetic conditions, some of which are very common. All thrombophilia (‘sticky blood conditions’) can cause problems for maintaining an adequate blood supply to the uterine lining and to the growing placenta leading
to increased rates of implantation failure and miscarriage.

Tests for acquired thrombophilia/ antiphospholipid antibodies etc.

These additional tests for thrombophilia may be available to you via your GP, but if not, can be arranged through our Doctor.

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 may be available to you via your GP, but if not, can be arranged through our Doctor.

Killer-Cell Immunoglobulin-like Receptors (KIRs)

KIRs are a family of protein receptors on the surface of NK cells, mostly inhibitory but some activating. There is an increased risk of implantation failure and/or miscarriage if particular members of the activating KIRs are missing. The risk can be reduced by using G-CSF (Neupogen).

Once we have identified the problem, we can provide relevant supportive immune therapy, for example Intralipids or IVIg infusions, Corticosteroids, Clexane, Progesterones and Lymphocyte Immune Therapy (LIT).

Please also refer to our Reproductive Immunology section for further information.