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Reproductive Immunology

What is Reproductive Immunology?

Reproductive immunology refers to a field of medicine that studies interactions (or the absence of them) between the immune system and components related to the developing fetus.

How does the Immune system function?

Your immune system is designed to fight infection and eliminate foreign organisms to prevent you from becoming unwell. The immune system fights toxins and infections with its army of immune system cells (NK) and chemicals (Cytokines). Research has shown that an “overactive“ immune system may negatively affect pregnancy outcomes.

The immune system has to learn to identify which Antigens are dangerous and which are not.

Embryonic cells antigens can be recognised as foreign or dangerous. Every pregnancy contains paternal DNA i.e. “foreign” to the female body.
During the first stages of pregnancy, a special mechanism gets activated to prevent the overreaction of the immune system and the attack to the fetus. When this preventing mechanism fails, failed implantation and miscarriage occurs.
There are different types of immune system responses that can cause reproductive failure. They do not exist in isolation but inter-connect in a way that perpetuates the vicious circle.

Reproductive immunology through blood tests identifies if immunological disorders may be contributing to recurrent IVF failure and miscarriages.

Who may benefit?

Immune testing and treatment is not recommended routinely for all patients. However for those who have suffered recurrent IVF failure or miscarriages it may increase the rate of successful embryo implantation resulting in a successful pregnancy.
Other indicators are

  • Associated or pre-existing auto immune conditions
  • Coeliac disease
  • Die off ratio (embryos not reaching transferable stage on Day 3)
  • Endometriosis

How is it identified?

Reproductive immunology covers various blood tests including;

Natural Killer (NK) cell number
The function of the natural killers is the ability to identify and then kill foreign or abnormal cells. Advances in immunology, the study of the body’s defence systems, enable us to understand how during pregnancy, the mother’s immune system is altered so that the foetus is not rejected by her body and allows the foetus to grow. The natural killer assay panel helps us to assess the ‘killing power’ of the natural killer cells that may be preventing the embryo from growing. It is advised that the natural killer cell activity is measured in women with a history of recurrent pregnancy loss and/or recurrent failed IVF’s.

Natural Killer (NK) cell toxicity
Implantation failure of the embryo might be the result of the environment in the uterus. Proteins (cytokines) are secreted by the endometrium which can result in a poor or anti-inflammatory environment. The cytokine blood test looks at these levels. If the NK numbers or cytotoxicity is high, we consider immune therapies.

Cytokine testing (Th1, Th2)
Th1 and Th2 cells are immune cells whose balance is vital for maintaining pregnancy. If you are producing too many Th1-type immune cells this may also reduce the chances of successful implantation and we may again recommend immunosuppression treatment.

The above are the main immune tests, other factors that may be considered (dependent on medical history) is thrombophilia and thyroid testing.

How is it treated?

Treatment will depend upon the results of the blood tests, and the actual levels of cytokines or natural killer cells. This can vary significantly between patients.

Treatment is planned to promote the correct immune response to prevent the rejection and increase the chance of implantation.

Raised natural killer cells will be treated with additional medication during your treatment cycles.
1. Steroids –Dexamethasone/Prednisolone
2. Clexane 40mg
3. Possible Intralipid / IVIG

Raised cytokines is treated with Humira and in some cases with intralipids instead of or as well as Humira.

It is important to discuss your treatment options with a doctor experienced at analysing the blood results and able to prescribe the most suitable treatment.

The blood samples are analysed by a specialist laboratory in Chicago and take approximately 2 weeks for the results.

For more information and guidance from the HFEA please follow this link: Immunological tests | HFEA