Causes of infertility

Immunological infertility

Immune system disorders may lead to reproductive failure at different stages of reproductive process: unexplained infertility, recurrent IVF or ICSI failures and recurrent miscarriage.

The immune system consists of immune cells and cell products (cytokines). Among the many different immune cells, two of these are associated with infertility, recurrent implantation failures and recurrent miscarriages. These are CD 56 (natural killer cells) which produce toxic cytokines including tumour necrosis factor (TNF) alpha and CD19 which produce antibodies to hormones such as HCG, progesterone etc.

Antibodies are substances produced by B lymphocytes (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.

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 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. Antiphospholipuid antibodies cause the woman’s blood to clot quickly cutting off blood supply to the baby.
• A mother may develop antibodies to her baby's DNA or DNA breakdown products such as ANA.
• Excess 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.
  

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