Immunological Infertility

Immunological infertility could explain why couples are trying to get pregnant and not being able to conceive, or when they conceive are unable to keep the pregnancy. Over the past few years, it has become increasingly clear that in a lot of cases, immunological issues play a major part in the above-listed issue. While it has been a fact that the principle of the immune system function was the ability to distinguish ‘self’ and ‘non-self’ (not as absolute as once believed), which is crucial in the body’s ability to recognize foreign or potentially threatening invasion by infection or cancer cells. 

In some instances, like in autoimmune conditions, the immune system starts attacking the body’s organs, leading to inflammation, damage and disease. In pregnancy, the placenta invades the lining of the uterus and is a potential threat to the health of the mother. The mother’s immune system is crucial in establishing a relationship that allows the fetus and the mother to thrive, so it must recognize it in a way that does not eliminate the fetus. 

What are the immune system’s mechanism of action?

The immune system has two mechanisms of action. They are cellular (type 1) and antibody (type 2). In a normal pregnancy, the placenta produces substances (especially progesterone) that cause a shift in the mother’s immune reaction, making it more type 2 dominant. This is because type 1 reactions are more dangerous to the pregnancy. This shift leads to changes in the immune responses in the sense that some autoimmune diseases like rheumatoid arthritis get better while others like Lupus can get worse. Also, specific antibodies can have harmful effects too, on both the fetus and the placenta.

How can the immune system affect fertility? 

While it is currently impossible to prove in any individual, the failure of the testis or the ovary can be a result of an autoimmune process. Anti-ovarian and anti-testicular antibodies can be detected in the blood of people who have failure of the ovaries or testis, respectively. However, the tests are neither sensitive nor specific, and this is not detected until very late, at the stage of complete ovarian or testicular failure when treatment is too late. 

The occurrence of sperm antibodies can happen in either the male or female partner and can be detected in the blood and/or the sexual secretions. The tests to detect this like, agglutination, or immobilization are difficult to carry out reliably. Some of them can only be done at a few specialist centres, and this can be provided by medical health travel agencies. They provide it as a form of overseas medical treatment which can be a form of medical tourism or health tourism. In the ejaculate, sperm antibodies can lead to infertility by affecting the sperm mobility or binding to the egg. 

What measures were taken to handle immunological infertility?

While it is unclear what level of antibodies is enough to need treatment, it is now known that immunosuppressive therapy does not improve fertility in this condition. Previous therapy involved the washing of sperm, which was followed by artificial insemination or IVF. The current treatment of choice, however, is the injection of a single sperm into a single egg (ICSI). 

Sperm antibodies in female sexual secretions are also capable of trapping spermatozoa, preventing them from progressing through the genital tract. There may also be instances where cytotoxic antibodies kill the spermatozoa. The therapy that has been tried for this condition is the prevention of sperm contact with the female genital tract by the use of a condom for some months, in the hope that the immune reaction will diminish. Then subsequent exposure will lead to fertilization before the immune response occurs again. 

Also, immunosuppressive therapy with corticosteroids has been reported after the fact with considerable success. But without a doubt, the most successful treatments are intrauterine insemination or IVF. Another instance where autoimmunity can affect a fetus is in the passive transfer of antibodies with toxic effects like in neonatal thyrotoxicosis, neonatal myasthenia gravis and neonatal lupus.

Antiphospholipid Syndrome (APS) 

Antiphospholipid antibodies are measured as either anticardiolipin antibodies or lupus anticoagulants. In women with reproductive failure and no other clinical issues, it is termed primary APS. In women with autoimmune diseases like systemic lupus erythematosus, it is called secondary APS. These antibodies have not been confirmed to affect fertility. However, they are found more often in women undergoing IVF, and they can directly affect placental cells. They are reliable predictors of adverse outcomes in pregnancy and have been associated with early and late-term fetal loss and other complications. The tests for these antibodies should be ordered in some of the following cases:

• Two or more first-trimester losses
• Repeated or severe pre-eclampsia
• Intrauterine growth retardation
• One or more second-trimester loss
• Thromboembolic disease in pregnancy
• Women with a systemic autoimmune disease who want to get pregnant

Some women with these antibodies will deliver successfully. However, treatment of the condition with aspirin and clexane has proved safe and effective in women with recurrent pregnancy loss. This treatment has not been proven to improve implantation in IVF or reduce the risk of pre-eclampsia or intrauterine growth retardation.

Natural killer cells 

These are types of white blood cells which are part of the nonspecific immune system. They are seen as the most primitive elements of the immune system, and their roles have been identified as early detection and elimination of cells that are not detected as self. Their mode of operation has also been detected as closely linked with type 1 immunity, and as such, they can be very threatening to a developing pregnancy. It has been proven that natural killer cells are likely to be intimately involved in the success or failure of implantation, causing both infertility and miscarriage. It has not been definitively proven that they cause reproductive failure.

Treatment of immunological causes of infertility

The only immunological condition that is widely recognized as treatable is antiphospholipid syndrome. The diagnosis of a high natural killer cell activity will usually be followed by the starting of any possible immune suppression therapy. During pregnancy, some of these options include:

• Prednisolone
• Progesterone
• Clexane
• Intravenous immunoglobin

The clinician in charge of these treatments should inform the patient of the side effects and the experimental nature of the therapy. Randomized trials have shown no benefit in immune suppression in cases of unexplained reproductive failure.