Immunological infertility
The immune system consists of immune cells (type of white blood cell) and cell products (cytokines). There are different immune cells such as natural killer cells (NK cells). NK cells are characterised by their expression of the cell surface antigens, CD56 and CD16. There are many types of NK cells producing variety of cytokines, some are beneficial protecting the body from developing cancer, and attacking infection while others produce toxic cytokines such as tumour necrosis factor (TNF) alpha. All NK cells originate from stem cells in the bone marrow and after maturation will either circulate in the blood or migrate and reside in tissues such as endometrium. Uterine NK cells are different from circulating (peripheral blood) NK cells.
At the time of implantation, a complex immunological interaction takes place between the embryo and immune cells of the endometrium “cross talk”. This is important for successful implantation and for continuation of the pregnancy. The interaction is done through exchange of cytokines.
Antibodies are substances produced by B lymphocytes (a type of immune cells) that circulate in the blood and body tissues, and which normally protect the body from invasion by foreign bodies such as bacteria and viruses, in order to prevent the body from getting an infection. For unknown reasons the body may develop antibodies to its own cells.
Immune system disorders may lead to reproductive failure at different stages of reproductive process: unexplained infertility, recurrent IVF or ICSI failures and recurrent miscarriage.
Causes
- Antisperm antibodies can be present in either or both partners. It can be present either in the blood or in the genital tract secretions such as cervical mucus and ejaculate. There are different types of antibodies e.g. IgG, IgA and IgM. Antisperm antibodies in the ejaculate will make the sperm ineffective by making them stick together and preventing them from being released. In the female, antisperm antibodies may interfere with the process of sperm transport and fertilization. Incidence 1-2%. The cause of antisperm antibodies is unknown, but there are associations with genital infection, trauma to the testicles, varicocele, vasectomy and after reversal of vasectomy.
- DQ alpha matching in the couple: Each person inherits two DQ numbers from his or her prospective parents. A pregnancy is recognised as foreign because the fathers Human leukocyte antigen (HLA) antigen is different from that of the mother. The mother makes blocking antibodies that attach to and camouflage the placenta (protecting antibodies). If the father‘s HLA is too similar to that of the mother, the embryo will not be protected because it will not be able to differentiate itself from that of the mother, leading to lack of blocking antibodies to protect the fetus and the pregnancy may fail.
- Antiphospholipids antibodies syndrome: Phospholipids are present on the cell membranes of all cells; they are glue molecules which play an important role in embryo implantation. Antiphospholipid antibodies (anticardiolipins and Lupus anticoagulant) cause the woman’s blood to clot quickly cutting off blood supply to the baby. Inherited thrombophilias (Factor V Leiden, prothrombin mutation, protein C, protein S, antithrombin deficiency etc) are associated with an increased risk of recurrent miscarriage and probably recurrent IVF failure .
- A mother may develop antibodies to her baby's DNA or DNA breakdown products such as ANA.
- Excess or hyperactive Natural Killer cells and or CD 19 cells: Natural killer cells
are good because they protect the body from developing cancer, infection
etc. However excess or hyperactive NK cells can damage the cells which
make the placenta and the endocrine system that produce hormones essential
for pregnancy. Some laboratories define the presence of more than 12% of NK cells in blood of woman with recurrent failed IVF as abnormal.