Immunological investigation

  1. The Role of the Immune System in Infertility

Disorders in the immune system can cause infertility in females. Immune system disorders and autoimmune conditions are behind about 20% of unexplained infertility cases. It can appear in many ways, like stopping an embryo from implanting or even causing a miscarriage.

In normal conditions, the body's immune system distinguishes between its structures and foreign substances. When it recognises foreign substances like infectious bacteria, the system produces antibodies and activates mechanisms to protect the body from any disease. 

However, the immune system works differently in a pregnant woman. After all, the embryo would carry a "foreign body" containing genes from a man, unknown to the immune system of her body.  

It is necessary for the woman's immune system to develop a mechanism of immune tolerance for a normal pregnancy and not attack the embryo. The function of erasing immunity cells so the embryo can develop in the womb is carried out by an antigen called HLA-G. 

However, any alterations in the immune system can affect female fertility to a great extent. If a woman's body recognises the embryo or sperm cells as foreign, it can lead to repeated miscarriages in the first trimester or implantation failures.

Because of this, it is essential to find out if there are any problems with the immune system when it comes to fertility. 

  1. Immunological Infertility Types

2.1 Anti-sperm antibodies

In females, anti-sperm antibodies are commonly found in cervical mucus. It prevents sperm cells from entering the uterus, leading to infertility.

If present, with intrauterine insemination (IUI), sperm can be inserted directly via a catheter into the uterine fundus. It will allow sperm to reach the egg without getting in touch with the sperm antibodies. In cases where they are spread across the female's reproductive system, in-vitro fertilisation is an effective treatment. Since the sperm cell is injected directly into the egg cell, it eliminates all chances of interaction with anti-sperm antibodies. 

2.2 Thrombophilias

Thrombophilia is an autoimmune condition in which the body develops abnormal blood clots in the vessels due to the loss of natural anticoagulants or mutations in their systems.

Though the condition may not seriously impact the body, in pregnant women, these blood clots can reach the placenta and block the fetus's development. 

The available treatment options include treatment with heparin and acetylsalicylic acid during the entire gestation. 

2.3 Antiphospholipid Syndrome

The immune system has antiphospholipid antibodies that can cause hypercoagulability. If such conditions arise during pregnancy, a woman's body may develop thrombi in the placenta, which can cause pregnancy loss.

The condition is an acquired thrombophilia that is behind more than 15% of cases of recurring miscarriage. Such alterations of the immune system require fertility treatment for a successful pregnancy. If there are no other fertility issues, a woman can carry the foetus and give birth with anticoagulant drugs and related treatment options. 

2.4 Alloimmune implantation dysfunction

In this condition, the pregnant woman's immune system recognises the embryo as a foreign body and produces antibodies against it. As a result, embryo implantation never happens, or pregnancy loss occurs. However, potential treatment options for this infertility cause are still under investigation. 

  1. Investigating Immunologic Infertility

Since the immune system is still complicated and cellular components causing infertility are still under investigation, there are only a few immunological investigations in place. 

However, an unexplained implantation failure in a couple might be due to abnormalities in the immune system. Getting a good diagnosis is recommended to determine the cause. 

Several tests are done when anti-sperm antibodies are suspected of causing infertility, including agglutination tests. There are two types of agglutination tests: macro and micro. Macro agglutination tests include assays like gel agglutination tests (GAT), mixed antiglobulin reaction (MAR), and immunobead tests (IBR, direct or indirect). Tray slide agglutination tests or micro tray agglutination tests are two assays for micro agglutination tests.  

Other tests include sperm immobilisation tests, antibody fluorescence studies via immunofluorescence (IF) or flow cytometry, colourimetry via ELISA or enzyme-linked immunosorbent assay, and radioimmunoassay via radiolabeled antiglobulin test. 

A proper combination of these tests can help healthcare professionals investigate immunologic infertility in females. 

In addition to these tests, immunological infertility can also be determined by investigating a large number of markers for an abnormal immune system. 

It can include markers for assays to determine autoimmunity (antinuclear antibodies, antiphospholipid antibodies, thyroid autoantibodies), inflammation assessments for C-reactive protein (CRP) and Interleukin-6 (IL-6, a type of white blood cell), and general markers like CBC with differentials and immunoglobulins (types of protein that produce antibodies).

It is known that any alterations of these parameters in the blood and those in the endometrium, the site where the embryo gets implanted, are not the same. Hence, it is recommended to determine all parameters directly via endometrial biopsy.

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