EXPENSIVE fertility treatments designed to suppress the immune system and supposedly help women who repeatedly suffer miscarriages early in pregnancy now appear to be based on bad science. A new study, the largest of its kind so far, shows that the blood test used to determine whether women should be given these treatments is ineffective.
The controversy centres around immune cells called natural killer (NK) cells. NK cells belonging to the mother are found close to the outermost layers of the embryo, and high numbers of them here have been linked to miscarriages. This has led a growing number of fertility clinics to offer tests to measure the level of NK cells in the blood. Women with an excess of such 鈥減eripheral鈥� NK cells are often then offered therapies such as steroids or immunoglobulins to dampen the immune system and reduce the number of NK cells in the uterus.
But according to Raj Rai and his colleagues at Imperial College London, testing for peripheral NK cells may be useless. Rai鈥檚 team took blood samples from 405 non-pregnant women who had experienced recurrent early miscarriage 鈥� a condition that affects around 1 in 50 women. They found that the number of peripheral NK cells in these women did not fluctuate with their menstrual cycles, unlike uterine NK cell levels, which are known to increase around the time of ovulation. This suggests that changes in levels of uterine NK cells are not reflected in the blood.
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The team confirmed this by taking uterine biopsies from 23 women at the same time as the blood samples. They found no correlation between peripheral and uterine NK cell numbers.
Rai鈥檚 team also studied 67 women with a history of recurrent miscarriage and found that peripheral NK cell numbers in women who subsequently became pregnant and gave birth to healthy babies were no different to those in women who continued to suffer miscarriages. 鈥淢easurement of peripheral blood NK cells is a poor predictor of pregnancy outcomes,鈥� says Rai, who presented the results at a meeting of the European Society of Human Reproduction and Embryology in Prague, Czech Republic, last month.
Emerging evidence suggests that it may be certain properties of NK cells, rather than their number, that determine the likelihood of miscarriage, says Anne Croy at Queen鈥檚 University in Ontario, Canada.
Croy took peripheral NK cells from women who were about to have embryos implanted following IVF treatment and tested how well they stuck to mouse uterine tissue. She found that NK cells from women who subsequently suffered miscarriages had slightly different patterns of 鈥渟tickiness鈥� to NK cells taken from women who carried their babies to term. 鈥淭his raises the possibility of a fertility test based on the ability of more and more of these cells to stick in consecutive blood samples,鈥� Croy says.
Nature's quality control
鈥淢ost women who miscarry think that their bodies are rejecting normal fetuses and that it鈥檚 their fault,鈥� says Siobhan Quenby of Liverpool Women鈥檚 Hospital in the UK. 鈥淏ut that鈥檚 probably completely wrong.鈥�
High levels of immune cells called natural killer (NK) cells in the uterus have been linked to miscarriages. Quenby believes that the cells may play a role in helping an unviable embryo to implant on the uterine wall temporarily. Rather than aborting during the very early stages of pregnancy, when it would not be noticed, the embryo remains for about six weeks, after which time its abnormalities begin to cause problems and a miscarriage occurs.
One previous study showed that there were more NK cells in the uterine linings of women who had miscarried abnormal fetuses than those who had miscarried normal ones, suggesting that NK cells may be making the womb too hospitable, possibly by increasing the blood supply to the embryo.
鈥淚t is a new way of thinking,鈥� says Quenby. 鈥淩ecurrent miscarriage may be a defect in nature鈥檚 quality control. It is the failure of the normal mechanism that prevents poor quality embryos from implanting.鈥�
