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Natural Killer Cell Testing

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.

Women who have fertility problems, specifically miscarriage or unsuccessful IVF are more likely to have higher levels of activity of these 'Natural Killer cells' [NK cells] than other women. High natural killer cell activity is a form of immunological infertility.

What this means for treatment is still not clear, but a number of different treatments are being trialled. NK Cells is an area of research being undertaken at IVFAustralia for patients who have experienced repeated miscarriage or repeated IVF failure.

How do we test for Natural Killer Cell activity?

Testing for Natural Killer Cell Activity at IVFAustralia involves a simple blood test to measure the number and activation levels of the Nkcells. 

The blood test can be performed as an alternative to, or in conjunction with, a traditional biopsy of the uterus. Your fertility specialist will decide which combination is best for you.  IVFAustralia’s laboratory at Greenwich offers the NK Cell Activity test by appointment only.

Who should consider Natural Killer Cell testing?

NK Cell Activity testing can be considered for patients in the following situations - recurrent miscarriage (defined as 3 successive miscarriages if aged less than 35 years, 2 successive miscarriages if aged over 35 years), repeated IVF failure (defined as 2 or more unsuccessful fresh IVF cycles), unexplained infertility (where a patient does not want IVF), patient request, future fertility concerns.

The process of measuring Natural Killer Cell activity

  1. Obtain a blood test request form from your fertility specialist
  2. Call IVFAustralia reception staff at any of our Sydney clinics, and book an Activated Natural Killer Cell blood test
  3. The test is available on Tuesday or Thursday between 8:30am and 12 noon
  4. Attend the appointment. Patients need to bring their blood test request form with them and present it to reception.  One small tube of blood will be collected for the NK Cell blood test.  If you have a referral for other tests these may be collected at the same appointment
  5. Results of the test will be sent to your referring IVFAustralia specialist
  6. Make an appointment for a follow-up visit to your fertility specialist for discussion of your test results and any advice on treatment therapies [as deemed appropriate].

The cost of the test is $295 to be paid at the time of your blood test.

More about Natural Killer Cells and their role

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 (recognisable as ‘non-self’, or separate from the mother) invades the lining of the womb and is a potential threat to the well being 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. This shift means that some autoimmune diseases that are predominantly cellular such as rheumatoid arthritis tend to get better during pregnancy. But it also means that antibody autoimmune diseases such as Lupus (SLE) can get worse, and specific antibodies can have their own harmful effects too – on both the placenta and the fetus.

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 to 70% of all cells. Uterine NK numbers start to decrease at 20 weeks of pregnancy and are absent at the end of pregnancy.

Testing for Natural Killer Cell Activity at IVFAustralia can be done by either a simple blood test or an endometrial biopsy.  Details of the blood test are below.

An endometrial biopsy is taken by a procedure that is similar to an embryo transfer, where a soft plastic catheter is used to gently aspirate a tiny piece of the uterine lining.  The biopsy is then sent off to the laboratory for testing.  The biopsy has to be done at the time of the month when implantation is taking place while the blood test can be done at any stage of the month. Your fertility specialist will decide which combination is best for you.

Their prime role appears to be the early detection (surveillance) and elimination (killing) of cells that are not recognised as ‘self’, such as infections or cancer.  Their killing capacity is also closely linked with cellular or type 1 immunity, and as such they are potentially very threatening to a developing pregnancy.  Given the role of NK cells in a woman’s immune system throughout pregnancy, current investigation into NK cells suggests they are intimately involved in the success or failure of embryo implantation, causing both infertility and miscarriage.  However, it should be emphasised that it is still unproven that NK cells do actually cause reproductive failure. Evidence is still of poor quality 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’.

Treatment for high Natural Killer Cell activity

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

  1. progesterone
  2. clexane
  3. prednisolone
  4. intravenous immunoglobulin (IVIG)

In prescribing any such therapy, the treating fertility specialist will carefully explain the 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, however research to date is promising.

Want more information?

If you have any questions about Natural Killer Cell Testing, the research A/Prof Gavin Sacks is leading in this area or you would like to book an appointment with any of our fertility specialists please call 1800 111 483.

Natural Killer Cells in Miscarriage

Natural Killer (NK) cells can affect embryo implantation, and cause miscarriage. There is a simple treatment available. Contact us.

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