A woman’s ability to successfully maintain a pregnancy is significantly influenced by a complex alteration of her immune system designed to prepare her body to host a developing embryo.
There are other immunological alterations that occur to protect the developing embryo, which is essentially a foreign organism developing within a woman’s body. In some cases these mechanisms do not work as intended and, depending upon the circumstances, might cause immune system disorders that result in recurrent miscarriages, infertility, or failure to conceive following IVF.
When should you consider immunological testing?
2 or more miscarriages after the age of 35 OR 3 miscarriages before the age of 35
2 IVF failures after the age of 35 OR 1 failed IVF before the age of 35
Poor egg production from a stimulated cycle (6 eggs or less)
Pre-existing immune problems (Lupus, Rheumatoid Arthritis, MS)
1 healthy pregnancy with all subsequent pregnancies ending in miscarriage
Endometriosis, especially stage 1 & 2
Cold and flu-like symptoms, sore throat noted regularly after ovulation, IUI, or IVF transfer
Family history of immune disorders, either side of the family
Immunological Fertility Tests
Anti-Beta2 Glycoprotein 1:
The presence of this antibody is an independent risk factor for thrombosis and pregnancy complications. It is a naturally occurring anticoagulant that may interact with other components involved in the blood clotting process causing abnormalities. This protein has also been shown to bind to phospholipids (major component of cell membranes) making them more susceptible to attack by antibodies. Damage done by these antibodies to cells involved in fetal implantation may cause pregnancy complications.
Detects atypical antibodies (IgG) during pregnancy. The technique is designed specifically to detect IgG antibodies, though on occasion, some other antibodies (IgM) may also be detected. Antibodies detected by the antibody screen will be subsequently identified, and further analyzed to determine if the antibody identified is considered to be clinically significant during pregnancy.
Anti-Cardiolipin Antibodies (ACA):
Cardiolipin is a phospholipid that is one of the main components of cell membranes. It is involved in essential cell functions necessary for proper embryo development. Elevated levels of antibodies to Cardiolipin may interfere with its ability to function normally and have been associated with vein or artery clotting, few blood platelets (fragments that lead to the formation of blood clots) and fetal loss.
An assessment of a woman’s immunological reaction to broken down DNA (histones). A positive result indicates the woman’s body may see embryos as foreign organisms and mistakenly mount an immune response in an attempt to rid the body of the embryo(s).
Microsomes are small cell particles. When these particles escape from damaged thyroid cells, the body produced microsomal antibodies that attack the thryoid gland. Measuring the levels of these antibodies can help detect thyroid problems.
Antinuclear Antibody (ANA):
These are antibodies that attack the nuclei (centers) of normal cells. These antibodies can destroy cells leading to problems similar to lupus, rheumatoid arthritis or other immunological diseases associated with recurrent pregnancy loss (RPL) or infertility. The ANA antibodies cause inflammation in the body or in the uterus during implantation. Many women with high levels of these antibodies are unable to become pregnant or carry a pregnancy to term as a result.
Anti-Ovarian Antibodies (AOA):
Antibodies directed towards the various parts of the ovary. This test measures the amount of AOA in the blood of a patient. AOA is most often found in cases of premature ovarian failure (POF), but has also been associated with unexplained infertility, PCOS and endometriosis. Elevated levels of AOA may impair the body’s ability to respond to attempts at ovulation induction.
Anti-Phospholipid Antibodies (APA):
Antibodies in the blood that attach to structures on the surface of cells called phospholipids. This blood test involves 3 different forms (IgM, IgG, and IgA) of antibodies against typically 3 different phospholipids (phosphatidyl ethanolamine, phosphatidyl inositol and phosphatidyl serine). Other less common phospholipids include: phospatidic acid and phosphatidyl glycerol. Result may be reported as negative, borderline, positive, weak, moderate or high positive. Positive APA reflects an increased blood clotting tendency that can cut off blood flow to the fetus. These antibodies can also cause the placenta to attach too weakly to the uterus.
Anti-sperm antibody (male):
This test looks for antibodies in semen that can damage or kill sperm resulting in reduced motility, interfering with egg fertilisation or even infertility. Normally, the testes contain a natural barrier that acts as a protective layer by preventing immune cells from gaining access to sperm within the male reproductive tract. However, the barrier can be broken when testicles are physically injured, after a surgery (biopsy or vasectomy) or after a prostate gland infection. This allows sperm to come into contact with the immune system resulting in the production of the antibodies. If a high number of sperm antibodies come into contact with a man’s sperm, it may be hard for the sperm to fertilize an egg.
Anti-sperm antibody (female):
This test looks for antibodies in blood that can damage or kill sperm resulting in reduced motility or interfering with egg fertilisation. A woman can have an allergic reaction to her partner’s semen and make sperm antibodies. This kind of immune response is not fully understood but may affect fertility.
An antibody, sometimes found in the bloodstream, that attacks a protein found in the thyroid gland called thyroglobulin. These antibodies can ultimately lead to the destruction of the thyroid gland. Measuring the levels of these antibodies can help detect thyroid problems. Also, antithyroglobulin antibodies can be found in women with infertility and recurrent miscarriages. One possible effect is the release of toxins when an embryo tries to attach to the uterus (embryo implantation) resulting in a miscarriage.
Embryo Toxic Factor (ETF):
Immunological factors have been implicated in a number of recurrent pregnancy loss (RPL) cases. ETF is actually two tests in one. In each case a woman’s immune cells are exposed to trophoblast (t he outermost layer of cells of the blastocyst that attaches the fertilized egg to the uterine wall ) antigens that are normally present when a developing embryo is present. Each test then measures how the woman’s immune cells response to exposure to these antigens. If there is no reaction, this indicates the potential for pregnancy success. Conversely, a reaction would indicate a potential immunological issue.
Human Lymphocyte Antigen (HLA) DQa:
These antigens are molecules on the surface of cells that determine an individual’s white blood cell type. One DQ antigen comes from the father and one comes from the mother, therefore this is a test for both males and females. It looks at the genotype of each partner. If the DQ genotypes are too similar, it indicates the potential for an adverse effect on early pregnancy due to a lack of immune diversity and protection.
Leukocyte Antibody Detection (LAD):
This test is used to determine the presence of anti-paternal lymphocyte (blocking) antibodies in the blood of pregnant women. During a normal pregnancy, the maternal immune system is down-regulated. In order for this to occur, a woman must produce blocking antibodies that prevent her immune system from attacking the embryo. These blocking antibodies are produced in response to a father’s antigens. Therefore, a positive test result demonstrating the presence of anti-paternal lymphocyte (blocking) antibodies is good.
Lupus anticoagulant testing is used to help determine the cause of an unexplained blood clotting, or recurrent pregnancy loss. It is a specific type of (antiphospholipid) antibody in the bloodstream that can cause abnormal blood clotting. Lupus anticoagulant is detected by measuring the time it takes for a sample of your blood to clot. If this process takes longer than normal, then it is likely lupus anticoagulant is in the blood.
Natural Killer (NK) Cells:
A type of cell that is part of the immune system. 80% of white blood cells in the placenta are NK cells. These cells are necessary to assist with implantation of the embryo. However, when activated, these cells also have the ability to kill trophoblast (t he outermost layer of cells of the blastocyst that attaches the fertilized egg to the uterine wall ) cells of a developing embryo. An excess of NK cells in the blood and uterus is correlated with pregnancy loss and reduced IVF success. They do this by interfering with implantation and embryo survival during pregnancy.
Reproductive Immunophenotyping (RIP):
This test looks at a broad range of immune cells that, when abnormally elevated, increase the risk of recurrent pregnancy loss (RPL). When elevated these cells may, either directly or indirectly, mount an immune response against a developing embryo.