Fertility Journal

Natural killer cells

A pregnancy is the ideal “transplant” because the mother does not reject it even though 50% of every baby’s genetic make-up is “foreign” coming from the father.  This led to the theory that there must be some form of suppression of the mother’s own immune system to prevent the rejection of every pregnancy.   It was also postulated that some fertility problems and miscarriages are due to a failure of this suppression mechanism, preventing the implantation of an embryo or the rejection of a pregnancy.  There is no robust evidence that supports the theory of immune rejection.

Natural Killer Cells

In the blood there are immune cells called lymphocytes.   About 5% of these lymphocytes have a special function:  to recognise and rapidly kill cells that have either become cancerous or have become infected with a virus.  They are known as “Natural Killer cells” or NK cells.   NK cells bind themselves to the diseased or infected target cells and release a potent cytotoxic chemical called tumour necrosis factor (TNF) that kills these cells.

NK cells form a normal part of our blood and play an important role in our bodies’ defence mechanism.

Uterine Natural Killer Cells

Recently, a special type of immune cell has been found in the endometrial lining of the uterus.  They are found particularly at the time of implantation of an embryo and during the early weeks of pregnancy.  Because of similarities in appearance to NK cells they were called Uterine NK cells.

However, uterine NK cells are very different from the NK cells found in the blood:

  • Uterine NK cells remain in the endometrium and do not appear in the circulation.
  • Unlike the blood NK cells, uterine NK cells do not kill other cells.

It is thought that uterine NK cells play an important role in implantation and in establishing the circulation of the early placenta.  No evidence has been produced to show that uterine NK cells have a damaging effect on the embryo or developing baby.

Fertility and screening tests for NK cells

The normal range of NK cells in the blood of healthy women varies from 5% – 30% depending upon the stage of the menstrual cycle at the time of testing.     A few clinics have established screening tests to measure the level of blood NK cells for patients with a history of infertility, failed IVF or recurrent miscarriages.

It is important to understand that levels of blood NK cells do not relate at all to any activity of uterine NK cells. Tests to measure blood NK cells are pointless for these groups of patients and are of no value in predicting the outcome of a future pregnancy.

On finding a raised level of blood NK cells, treatments have been offered to reduce the levels in the belief that improved pregnancy outcomes will be achieved.  These have included treatments with steroids, intravenous immuno-globulin (IVIG), and tumour necrosis factor blocking agents.

These potent treatments are not without risk to either yourself or to your pregnancy.  If you are offered such treatments you should discuss the rationale and safety aspects with your specialist.   You must be very clear about the benefits that are expected and balance these against the degree of risk.    The investigations and treatments are likely to be expensive.

Couples in these situations are very vulnerable to anecdotal claims of successful treatments.   Major international studies (Cochrane Collaboration) have stressed that the screening tests “are of no predictive value for pregnancy success”  and  should be abandoned.   A report from the Royal College of Obstetricians & Gynaecologists (2008) has brought attentiion to the fact that some couples are being misled by the few clinics promoting these tests and are paying too much for unnecessary tests and treatments, many of which are of no proven value.

It must therefore be concluded that tests and treatments should be withheld until proven to be of benefit by suitable randomised clinical trials.