Overview of Reproductive Immunology
I. Indicators for Immune Testing
The indications are as follows:
(a) two miscarriages or two IVF failures after age 35
or three miscarriages or IVF failure before age 35,
(b) poor egg production from a stimulated cycle (less than 6 eggs),
(c) blighted eggs,
(d) idiopathic (unknown cause) infertility,
(e) previous immune problems (ANA positive, rheumatoid arthritis, and/or lupus),
(f) previous pregnancies that have shown retarded fetal growth, and
(g) one living child and repeat miscarriages while attempting to have a second child.
II. Immune Testing
A Reproductive Immunophenotype
This test measures the percentage of lymphocyte types in the blood. These include CD-3, CD-4, CD-8, CD-19, CD-5, CD56, CD16. See: Immunophenotype.
B. Antinuclear Antibodies (ANA)
This test checks for problems similar to lupus and rheumatoid arthritis or other similar immunological diseases that can also result in pregnancy losses or infertility. This test becomes weakly positive in women with infertility and in women with recurrent pregnancy losses. It is usually reported as ANA positive with at titer 1:40 or higher with a speckled pattern. This pattern is not typical of lupus or rheumatoid arthritis or other immunological disorders.
C. Anti-DNA/Histone Antibodies
A person may develop antibodies against components of the nucleus. The best known component is DNA. But there are other components such nuclear proteins that include "histones". When a person has antibodies to nuclear constituents, it may be a sign that they have autoimmune disorders. These are abnormal responses where the immune system attack one's own body. Such conditions are increased in frequency in women with recurrent pregnancy loss.
D. Antiphospholipid Antibodies (APA)
A very important group of molecules found at the surface membrane of cells are phospholipids. Antibodies that are directed against these molecules can increase the risk of blood clot that may be associated with recurrent pregnancy loss.
E. Natural Killer Cell Assay
Natural killer cells are members of a type of white blood cell known as "lymphocytes". They perform a number of very important functions including survaillance against cancer cells and infection. However, there is evidence that excess activity in women of reproductive years can be associated with recurrent pregnancy loss. We can test for their activity in the laboratory. See: NK Assay.
F. Th1/Th2 Cytokine Assay
Another group of lymphocytes, known as T cells, can be divided by the functions they carry out. Those that orchestrate immune responses that attack cells that are infected or abnormal are known as "Th1 cells". Other lymphocytes that tend to oppose the responses of Th1 cells are known as "Th2 cells". A natural balance is established by each person and can be formulated in the ratio of Th1 cell numbers to Th2 cell numbers (the "Th1/Th2 ratio"). It is important to establish the Th1/Th2 ratio because women with high ratios can be treated. See: Th1 Th2 Assay.
G. T regulatory cells (Treg)
A new group of T cells has recently been defined within the broad category of lymphocytes. These cells are thought to perform a very important role in controlling the natural tendancy of the woman's immune system to reject the semi-foreign fetus. These cells are known as "T regulatory cells" or "Tregs". Higher numbers of Tregs in the blood have been associated with better pregnancy outcome. Measures of Tregs in the endometrial lining have also been shown to be associated with better pregnancy outcome. We at the center are now studying Tregs both in endometrial biopsies and in the blood of patients before and following therapy. See: T regulatory cells.
Increased tendency for the blood to clot is called thrombophilia. Throughout an entire normal pregnancy, the mother's ability to produce blood clots in the uterus and the placenta is suppressed. Some mothers may have certain conditions, both acquired and inherited, where clotting of the blood nourishing the baby is not suppressed. This can contribute to many pregnancy complications.
We test for many of these thrombophilia conditions. See: Thrombophilia: Inherited and Acquired.
I. Elevated CD57 cells in the endometrium
Patients can undergo an endometrial biopsy (lining of the uterus) to test for two types lymphocytes: CD57+ cells and T regulatory cells. High levels of CD57+ cells may be associated with increased risk of infertility and loss. See: Immune pathology of the endometrium.
J. Other Tests
It is important that the woman have other tests that are widely available in all laboratories. These may include the Lupus Anticoagulant Antibody, APTT (a blood clotting test), antiovarian antibody test (AOA) and an antithyroid antibodies (ATA) among others. Our doctors can help advise about the relevance of these tests.