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Natural born killer cells

October marks pregnancy and infant loss awareness month, so we wanted to look at the role of Natural Killer cells in pregnancy and their relationship with recurrent miscarriage.

Pregnancy is a state when the usual laws of biological function are bent in strange ways. This is especially true for the female immune system, which now has to accommodate a foreign body living within her own body.

The first question is, why is this situation tolerated at all? After all, a baby has two parents so 50% of it, by definition has nothing to do with the mother. Under normal conditions that 50% would be instantly rejected by the mother’s immune system.

This is because the immune system protects us from foreign matter such as viruses, bacteria and allergens. It also protects against truly foreign bodies such as dirt, bullets, bee stings and splinters.

So why does the mother’s immune system not reject the embryo immediately after implantation takes place?

This is where NK-cells come in. NK-cells are white blood cells, they kill foreign cells by releasing granules. These granules invade the foreign cell and destroy it from the inside.

A natural killer cell (NK-cell)

Pregnancy requires that the mother’s immune system is suppressed. The female body produces TWO types of NK-cells:

  • Peripheral NK-cells (pNK-cells): these are the ones in normal circulation
  • Uterine NK-cells (uNK-cells): these are produced in uterine tissues and gather in the implantation site.

uNK-cells help the uterus to adapt allowing growth of the foetus and they don’t destroy foreign cells.

NK-cells and their effects on fertility and pregnancy

For many years there was controversy over the role of NK-cells in fertility and pregnancy. But in 2014 some light was shed in this area. Researchers reviewed all the studies to date and looked at three areas:

  • What are the levels of the different types of NK-cells in infertile versus fertile women?
  • What is the association between the different types of NK-cells and IVF outcome?
  • What are the levels of the different types of NK-cells in women with recurrent miscarriage?

In order to answer these questions, the researchers reviewed 22 studies and accessed five extensive electronic medical databases.

What are the levels of the different types of NK-cells in infertile versus fertile women?

The researchers said, “Pooling of studies that reported peripheral NK­-cells. The numbers showed significantly higher NK cell numbers in infertile women compared with fertile controls.”

So, an association between p-NK-cell level and infertility was observed.

What is the association between the different types of NK-cells and IVF outcome?

The researchers said, “Meta-analysis of studies that evaluated the role of NK-cells in IVF outcome showed no significant difference in live birth rates in women with elevated NK-cells. Nor NK-cell activity compared with women without elevated peripheral NK-cells or NK-cell activity.”

So, no association between raised/lowered NK-cells and IVF birth success was noted.

What are the levels of the different types of NK-cells in women with recurrent miscarriage (RM)?

The researchers said, “Meta-analysis of studies that evaluated peripheral NK cell percentages in women with RM versus controls showed significantly higher NK cell percentages in women with RM.”

So, women with high levels of peripheral NK-cells do seem to demonstrate a higher level of repeat miscarriage than those who do not have high levels.

However, the researchers caution against using NK-cell tests as a predictor of infertility, miscarriage or IVF success. More research is needed to determine the specific role of uNK-cells and the effects of raised pNK-cells.

Real world considerations

For couples trying to conceive, it is natural that they would want to maximise their chances for success.  Further investigative research as that could take years, so some clinics offer NK-cells levels testing. But, as mentioned, IF testing is undertaken it is important to distinguish between the two different types of NK-cells and to bear in mind that NK-cell level is not a predictor of overall IVF success according to the 2014 review of 22 studies.

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