The Role of Natural Killer Cells in Recurrent Implantation Failure in Women Undergoing Treatment using Assisted Reproductive Techniques

What is the purpose of this study?

During pregnancy the foetus develops in the womb attached to the mother’s blood supply. This is a unique situation when a tissue, which is substantially different from that of the mother, survives for a long period without rejection. The mechanisms that allow this process to happen are far from understood.

Recently a specific type of cell in the human immune system, so called Natural Killer (NK) cell, have received attention both in the scientific community and in the media. Small studies claim that increased numbers or increased activity of NK cells in the mother’s blood may result in the failure of a fertilised egg being implanted in the lining of the uterus, potentially causing infertility or poor outcome in vitro fertilisation (IVF).

To the contrary, NK cells present in the lining of the womb have been claimed to be beneficial for the development of pregnancy, by supporting the development of the placenta. A lack of such cells in experimental animals causes abortions or results in small babies.

There are several treatment options offered to women wishing to become pregnant via assisted fertility, such as IVF or intrauterine insemination. However, the scientific justification of these treatments is weak while the risks could be substantial.

The purpose of this study is to investigate further whether measuring the characteristics of NK cells either in the blood or the womb of non pregnant women could be used to identify individuals who are likely to experience problems in conceiving.

Women who have a history of failed pregnancies or failed IVF attempts. And those with a number of successful pregnancies without complications (controls) are include in the study. Individuals in these two groups (controls vs patients with miscarriages/failed IVF attempts will be compared to see whether there are differences in the number, characteristics or functional activity in the blood or womb-derived NK cells between the two groups.

Participation is entirely voluntary. If patients agree to take part in the research study during their surgery a small amount of tissue from the lining of your womb is sampled.

What do the patients have to do?

In patients undergoing laparoscopy - during the laparoscopy, it will be necessary to visualise the neck of the womb (the cervix), and an instrument will be inserted into the neck of the womb to enable us to move the womb slightly to access the fallopian tubes more easily from above. At this stage of the procedure we would like to insert a fine biopsy sampler through the neck of the womb to allow us to sample the cells from the lining if the womb. It is a little like having a cervical smear taken. This will be done whilst you are under anaesthetic and will take no longer than a couple of minutes.
In patients who have had failed pregnancies (miscarriages) or failed IVF treatment – a sample will be taken in a similar way to a cervical smear. Cells from the lining of the womb are sampled using a fine sampler that is passed through the neck of the womb (the cervix). You may experience some mild discomfort similar to period pain whilst the sample is being taken.
We would like to ask both control individuals and patients with failed pregnancies or IVF attempts to also give 20 ml (approximately a tablespoon) of blood.
What are the benefits of taking part?

By taking part you will help us to establish whether changes in NK cell numbers, characteristics or functional activity contribute to a high risk of implantation failure. This information will help us develop new therapies helping infertile women in the future. However, it is a long term goal that will require the participation of hundreds of patients in the future.

What will happen to the results of the research study?

The results will be published in international research journals. At this point only statistical data will be presented. There will be no way that you could be identified as an individual. Also the findings will be used in applications for further research funding. Again, your name or other personal details will not be released to anyone in this process.

Who is organising and funding the research?

The study is being organised by Liverpool Women’s NHS Foundation Trust and the University of Liverpool.

Who has reviewed the study?

The study has received favourable ethical approval from an independent Research Ethics Committee.

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