Natural Killer Cell Activity Investigation

Immune cells in the uterus are important in the early detection and elimination of foreign cells, such as infections or cancer. These immune cells are normally present in every person as part of their immune system. ‘Natural Killer cells’ (NK Cells) play an important role in the immune system responses to viral infections as well during implantation. Some women who have fertility problems, and specifically recurrent miscarriage or failed IVF, are more likely to have higher levels of activity of these NK cells than other women. What this means for treatment is still not clear, but a number of different treatments are being trialled.
Testing for Natural Killer Cell Activity involves a simple blood test to measure the number and activation levels of the NK cells. The blood test can be performed as an alternative to, or in conjunction with, a traditional endometrial biopsy of the uterus.

An endometrial biopsy can be taken via a soft plastic catheter that is used to gently aspirate a tiny piece of the uterine lining as an awake procedure, or under general anaesthetic as part of a hysteroscopy. The biopsy is then sent off to the laboratory for testing. The biopsy has to be done at the luteal phase of the month (around Day 21 in a 28 Day cycle) while the blood test can be done at any stage of the month. Your fertility specialist will decide which combination is suitable for you.

NK Cell Activity testing can be considered in the following situations:

  • recurrent miscarriage (defined as three successive miscarriages if aged less than 35 years, two successive miscarriages if aged over 35 years)
  • repeated IVF failure (defined as two or more unsuccessful fresh IVF cycles)

About Natural Killer Cells

Immune factors affecting pregnancy

The body’s immune system includes among its functions the ability to recognise ‘foreign’ or threatening invasion by infection or cancer cells. In some instances (called autoimmune diseases) the immune system mistakenly recognises and attacks ‘self’, and this leads to inflammation, damage and disease.

Pregnancy is a unique situation in which the placenta invades the lining of the womb and is a potential threat to the wellbeing of the mother. The mother’s immune system must recognise that threat, but also respond in such a way that does not eliminate it. The mother’s immune system is critical in establishing the relationship between the mother and the fetus that allows both to flourish.

The immune system has two main mechanisms:

  1. cellular (type 1); and
  2. antibody (type 2)

In normal pregnancy, substances produced by the placenta (particularly progesterone) cause a shift in how the mother’s immune system behaves so that it becomes ‘type 2 dominant’. This is because type 1 responses are potentially more dangerous for the pregnancy. People with autoimmune diseases, such as Lupus, rheumatoid arthritis tend to have high levels of anti-nuclear antibodies, that can lead to inflammation of the uterus and placenta, implantation failure and recurrent miscarriages.

Natural Killer Cell Activity

Natural Killer cells are the main immune cell-type found in the uterus. Their numbers increase through the menstrual cycle to peak at the time of implantation of an embryo. If an embryo does implant, NK numbers increase further. Uterine NK numbers start to decrease at 20 weeks of pregnancy and are absent at the end of pregnancy.

Their prime role appears to be the early detection (surveillance) and elimination (killing) of cells that are not recognised as ‘self’. Their eliminating capacity is also closely linked with cellular or type 1 immunity, and as such they are potentially threatening to a developing pregnancy. Given the role of NK cells in a woman’s immune system throughout pregnancy, current investigation into NK cells are looking at the link between the success or failure of embryo implantation and miscarriage. However, it should be emphasised that it currently is still unproven as to whether NK cells do actually cause reproductive failure.

The current evidence is still very limited and it is certainly possible that the studies so far simply describe an ‘association’ between NK Cell Activity and reproductive failure rather that a specific ‘cause-and-effect’.

Natural Killer Cell Activity Treatment

For patients with a diagnosis of high ‘Natural Killer Cell Activity’ possible immune suppressive therapy is recommended. These options include:

  1. progesterone
  2. clexane
  3. prednisolone

In prescribing any such therapy, we will carefully explain the potential side effects and experimental nature of the treatment. Further research is needed to determine the impact of immune suppression in women with high Natural Killer Cell Activity.