Researchers investigating recurrent miscarriages have made the intriguing discovery that the steroid prednisolone reduces the numbers of a type of cell that is known to play a role before and during early pregnancy. Their findings open up possible new avenues for treating a condition for which no satisfactory treatment currently exists.
The research is so important that the lead author, Dr Siobhan Quenby, told the 21st annual conference of the European Society of Human Reproduction and Embryology: "A randomised controlled trial of prednisolone for the prevention of miscarriage is urgently needed and I am in the process of setting one up."

However, Dr Quenby, who is a senior lecturer and honorary consultant in the Department of Developmental and Reproductive Medicine at the University of Liverpool, UK, warned that her research was still at an early stage and that she did not want women to be given false or premature hopes.

"This is very exciting data, but the research is at a preliminary stage, so I cannot recommend it to patients without a proper trial. It is important that, in the excitement of new hope for these poor women for whom there is no treatment currently available, neither myself nor the media over-exaggerate the results."

Recurrent miscarriages (i.e. three or more losses) affect two in every 100 women of reproductive age. "It is a distressing condition that presents a challenge for clinicians and immunologists. Recent research has pointed to a significant role for uterine natural killer (uNK) cells in pregnancy implantation," said Dr Quenby.

uNK cells are the most numerous white blood cells found in the uterus and in the special lining of the uterus that occurs during pregnancy (the decidua). They are found close to the outermost cells of the developing early embryo that go on to develop into the placenta. Previous research has shown that there are increased numbers of uNK cells in women who suffer from recurrent miscarriages (RM), and that the cells have steroid hormone receptors on their surface.

Dr Quenby and colleagues decided to see whether prednisolone could reduce the high numbers of uNK cells in the endometrium (womb lining) of women with RM. They recruited 110 women who had severe RM (an average of six miscarriages, with a range from three to 22), with no known cause and with regular 28-day menstrual cycles. They took endometrial samples and tested them to identify the quantity of uNK cells. Any women whose endometrial cells contained more than the normal range of uNK cells (more than five per cent) were offered 20mgs of oral prednisolone for 21 days from the start of their menstrual cycle. Out of a possible 33 women with uNK cells greater than five per cent, 29 agreed to take prednisolone and then the researchers took a second endometrial sample by biopsy on day 21.



"We found that the prednisolone significantly reduced the number of uNK cells in the endometrium. The women had an average of 14 percent before treatment, with the highest percentage being 72 percent, and after treatment the average dropped to nine per cent," said Dr Quenby.

"Although nine per cent is still higher than the normal average of five per cent, these women only took prednisolone for three weeks. In practice, they would have to take the steroid for longer before conception occurred, probably for about three months.

"This research has demonstrated that high numbers of uNK cells in the pre-implantation endometrium of women with RM can be reduced by administering prednisolone. However, we do not know the exact role played by uNK cells in implantation and pregnancy yet.

"We know that, normally, uNK cells increase during the menstrual cycle and are at their most numerous at the time of implantation of the embryo when they make up about 25 percent of the endometrium. If pregnancy occurs, then their numbers increase during the early stages and they interact directly with the foetal placental cells (the trophoblast). This would suggest that they might play a positive as well as negative role during early pregnancy. There is no evidence that uNK cells actually attempt to kill the trophoblast, despite their name, but they may prevent the trophoblast invading too far into the endometrium ? too extensive an invasion can cause the women to die of choriocarcinoma (cancer of the placenta).

"We also know that pregnancy can occur without uNK cells, because embryos occasionally implant and grow to full term outside the uterus where there are no uNK cells.

"There are many unanswered questions at present, and we hope that randomised controlled trials will shed more light on the mechanisms involved and whether the use of prednisolone may, in fact, represent a new and effective treatment for recurrent miscarriages." PregnancyAndBaby.com

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