What role does the immune system play in fertility?

From an immunological point of view, pregnancy is a unique set of circumstances because a woman’s body has to ‘withstand something that is foreign to it’. The mother has to carry the embryo and, in order to do so, her immune system needs to accept co-existence with cells that are at least half foreign in origin. Using a silencing and inactivation mechanism (about which we still have a lot to learn), as tissue that belongs to the embryo, the placenta invades the maternal tissue but is not rejected. Therefore, the embryo implantation process and correct development of the pregnancy depend on a delicate balance that allows two immunologically different individuals to tolerate one another.

The immune system protects the organism from foreign cells and from illnesses. A group of immune cells – the most understood of which are antibodies – react to viruses, bacteria, parasites and even an organism’s own abnormal cells such as cancer cells. The system is responsible for rejections during transplants and transfusions when it detects cells that belong to another individual. Sometimes, the immune system reacts incorrectly to its own normal cells and destroys them, resulting in diseases that are known as autoimmune diseases.

Recurrent implantation failure (a failure to get pregnant following several transfers of suitable embryos) or recurrent pregnancy losses (two or more involuntary pregnancy losses) are two of the situations that we face on a daily basis. They are both disappointing and difficult for patients and doctors. Our knowledge of this remains incomplete but its characteristics suggest that the immune system could be involved.

So far, Antiphospholipid syndrome is the only immune disorder that has been clearly linked to an elevated percentage of failures to reproduce. It is the most common demonstrated cause of recurrent pregnancy loss and it can be treated. The illness is characterised by the presence of the mother’s blood in some antibodies known as antiphospholipids. They cause thrombotic events in the placenta that lead to pregnancy loss. Treatment with aspirin and heparins (Clexane®) has proven to be successful in reducing the risk of pregnancy loss.

The other main area of research in the field of reproduction immunology focuses on the cells in the immune system.

The treatment that is currently available aims to stop or control abnormalities in the immune system and any other abnormalities that are present. Corticosteroids, intravenous immunoglobulin, Intralipids and anti-TNFs are amongst the pharmaceutical drugs that can be used. They can all be used with or without heparin, which also appears to have a modulating effect on the immune system, and aspirin.

The use of pharmaceutical drugs is still being researched and the results vary.

Research into the immune system and infertility has progressed but it remains limited. Whilst they may be a starting point, they do not represent unquestionable scientific evidence and, as such, it is not possible to standardise use in day-to-day clinical practice.

Despite this, doctors continue to search for answers and treatment for these situations that are so frustrating and painful for our patients. We hope that our current research projects will soon give us an improved understanding of the situation and solutions for it.

Dr Ángela Llaneza, a gynaecologist at Instituto Bernabeu.

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What role does the immune system play in fertility?
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