Reproductive immunology

Some fertility clinics offer tests and treatments which are based on the idea that immune cells in your body can ‘reject’ a fetus, preventing a successful pregnancy. This is an area of medicine called reproductive immunology and the treatments are called immunosuppressive therapies.

The theory behind reproductive immunology has been widely discredited, and there is no evidence that immunosuppressive therapies improve your chance of getting pregnant.

We do not believe that immunosuppressive therapies should be offered to patients unless they are taking part in a clinical trial.

On this page:

What is reproductive immunology?

Reproductive immunology is concerned with the way a woman’s immune system reacts if she becomes pregnant.

Usually, your immune system works by fighting off any invading cells that it doesn't recognise because they don't share your genetic code. Some scientists have suggested that ,the same thing may happen to a fetus because it has a different genetic code from its mother’s. A woman’s body may ‘reject’ the fetus because her immune response is not being properly suppressed.

This theory has been widely discredited and there is no convincing evidence that immune rejection of the fetus ever happens in women with fertility problems. Instead, scientists now know that during pregnancy, the mother's immune system works with the immune system of the fetus to help the placenta develop.

The information below is based on the latest research and expert views about reproductive immunology (to February 2015). 

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Why may I be offered tests and treatment on my immune system?

Some fertility clinics offer tests to women who have had several miscarriages or a number of unsuccessful IVF treatments.

Many of these tests assess the number or activity of immune cells called natural killer (NK) cells. If these tests show your NK cell number or activity is ‘high’ you may be offered an immunosuppressive therapy to reduce these levels. However, there is no strong evidence that high numbers or activity of NK cells is problematic. 

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What treatments are offered and what are their possible side effects?

Treatments to suppress NK cells offered by some clinics include:

  • steroids
  • intravenous immunoglobulin (IVIg)
  • tumour necrosis factor-a (TNF) blocking agents
  • intralipid infusions.

These treatments are not licensed for use in fertility treatment. As with all medicines, they carry risks and potential side effects and your clinic should tell you about them. You should only have treatment after giving fully informed consent.

Corticosteroids are a type of drug that can suppress immune responses, and are routinely used in the treatment of arthritis, asthma and other autoimmune disorders.

There is no proven advantage in using steroids in the first three months of pregnancy, and the risks to you and your baby outweigh any possible benefits. Medical guidelines recommend that pregnant women avoid all drugs at this stage unless they are likely to benefit your health.

A clinical trial in Canada tested the effect of giving pregnant women who had previously suffered two or more unexplained miscarriages a corticosteroid called prednisone. The study found that prednisone didn’t prevent miscarriage, and increased the risk of high blood pressure, diabetes and premature birth.

Intravenous immunoglobulin (IVIg)

IVIg is made from antibodies and is usually given by intravenous drip as a treatment for immune deficiencies and autoimmune diseases.

A recent review of several clinical trials found that IVIg treatment did not increase IVF success rates. Another similar review recommended that IVIg for recurrent miscarriage should not be offered unless it is done as part of a clinical trial.

IVIg carries varied and sometimes unpredictable risks. Side effects are rare but can include headache, muscle pain, fever, chills, low back pain, thrombosis (blood clots), kidney failure and anaphylaxis (a bad reaction to the drug).
It is also possible that, antibodies from IVIg may cross the placenta into the bloodstream of the fetus during pregnancy, where they might react against some of the baby’s cells. However, this has not been seen in practice.

TNF-a blocking agents
Tumour necrosis factor (TNF) is a chemical produced by immune system cells, such as NK cells, which help immune cells get to the source of infections by promoting inflammation. Drugs which block the effect of TNF (known as TNF- blocking agents) are routinely used in the treatment of arthritis, asthma and other immune disorders. They stop inflammation but make the attack on infection less effective.

Several clinics offer the use of TNF- blocking agents (Enovel, Remicade and Humira). However, there are risks:

  • Remicade may increase the risk of septicaemia, chronic infections such as tuberculosis, cancer of the lymphatic system, liver problems, white blood cell disorders and strong reactions to the drug..
  • Medicine specialists say that Remicade should not be used in pregnancy.
  • Humira is not licensed for use in implantation failure (when the embryo fails to embed itself in the lining of the womb). Its effects on reproduction and fetal development are unknown.

Intralipid infusions

Intralipid infusions are a sterile fat emulsion, containing soybean oil, egg yolk, glycerin and water, which is administered by injection.

In April 2015 the Royal College of Obstetricians and Gynaecologists said that there is no rationale for the use of intralipid infusions in fertility treatment. There are no published randomised controlled trials assessing its efficacy.’

The risks associated with the use of intralipid infusions:

  • severe sepsis (also known as blood poisoning) - this is a potentially life-threatening condition in which the body’s immune system goes into overdrive. This can reduce the flow of blood to vital organs, such as the brain and heart. Three women have developed severe sepsis following administration of intravenous intralipid infusions. This is believed to be as a result of poor practice in the administration leading to contamination of the product.
  • hypercoagulation – this is excessive blood clotting, which can result in blood clots forming inside blood vessels. This can be dangerous, increasing the risk of deep vein thrombosis, stroke and miscarriage.

There have been no animal studies on the use of intralipid infusions and it is not known whether they can cause fetal harm when given to a pregnant woman or can affect her chance of getting pregnant in the future.


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What should I ask my doctor?

If you are recommended immunological treatments as part of your fertility treatment, we advise you to make sure you feel properly informed about the risks of the tests and treatment.

Your clinic should explain:

  • why they think the tests and treatment may help you
  • what the risks and side effects may be
  • how much the treatments will cost.

Remember that treatments can only be properly assessed in the context of a proper clinical trial. Stories about individual women who have achieved a successful pregnancy after receiving these treatments do not prove that the treatments were effective. Without a proper clinical trial there is no way to assess whether a particular treatment has had any benefit.

Before agreeing to any immunological treatment, it is important to talk through all these topics with your clinic. You also need to have had an opportunity to weigh up all the issues, and you should feel happy with your decision.
Questions you may want to ask include:

  • Why do you think I need this treatment - can you explain what you think is happening in my body? 
  • What data or evidence do you have to prove that this treatment will improve my chance of having a baby?
  • What will the treatment involve for me?
  • How much difference do you think having this treatment will make for me?
  • What are the side effects and risks of the treatment?
  • How much will the tests and treatment cost me?


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Where can I find out more about these treatments?

If you want to dig a little deeper into the views of expert bodies, you can read the following research reports:

The Cochrane review, Immunotherapy for recurrent miscarriage, Wong LF et al,. Cochrane Database Syst Rev 2014

The Cochrane Collaboration is a group of over 15,000 contributors in more than 100 countries. They apply a rigorous, systematic process to review the effects of medical treatments tested in randomised controlled trials. Cochrane reviews are considered to be a reliable source of evidence in healthcare.

Immunological testing and interventions for reproductive failure, Royal College of Obstetricians and Gynaecologists Scientific Advisory Committee , June 2008.

Medical adjuncts in IVF: evidence for clinical practice, British Fertility Society Policy and Practice Committee, Human Fertility, March 2009; 12(1): 1–13

If you want to dig a little deeper into the science of reproductive immunology you can read the following research reports:

Moffett A and Colucci F. Uterine NK cells: Active regulators at the maternal-fetal interface. J Clin Invest 2014; 124(5): 1872-1879

Seshadri, S., & Sunkara, S. K. (2013). Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Human Reproduction Update, 20(3), 429–38. doi:10.1093/humupd/dmt056 

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Page last updated: 24 September 2015