Cheap drug could prevent some recurrent miscarriages

In 2003, Siobhan Quenby and her research team reported a new and promising practical finding in human developmental medicine.  The research is still in its early stages, but if proven this could provide a cheap and easy way to reduce the incidence of recurrent miscarriages.

In about 50 per cent of all cases of recurrent miscarriages, the miscarriages are of unknown cause (in medical language, they’re idiopathic).  Earlier research had suggested that the cause might often be a failure of the natural regulation of the pregnancy resulting in an excess of Natural Killer (NK) cells.  NK cells are a part of the autoimmune system that are believed to be essential for controlling uterine inflammation as part of normal fetal development.  However in excess they could be implicated in the miscarriage by sabotaging the pregnancy.

Quenby’s team found one patient in her practice at the Liverpool Women’s Hospital who had had 14 consecutive miscarriages, each occurring between 8 and 10 weeks of gestation.  On full investigation she was diagnosed with idiopathic recurrent miscarriage.  Treatment with low dose aspirin and folic acid failed to prevent two further early miscarriages of apparently healthy fetuses.

Consent was obtained to perform a mid-luteal phase endometrial  biopsy.  This is a tissue sample from the inner part of the uterus, normally taken using a catheter, during the period when the endrometrium, the wall of the uterus, thickens to prepare for implantation of any fertilized eggs, thus beginning pregnancy.  The result was that they found “Thirty-one percent of this patient’s endometrial cells were uNK cells”

Offered a choice of treatments, the patient opted for 0.5 mg per day prednisolone, a corticosteroid, pre-conception.  She had three further miscarriages, at 5-6 weeks.  The dosage was increased to 20 mg per day.  She had a survival, a daughter delivered by Caesarean section at 32 weeks of gestation, with a birth weight of approx. 1.5Kg.  Tests showed that her bone density was apparently not adversely affected by the prednisolone (this is a known risk from steroid treatment).

Next Quenby’s team recruited eighty-five women with idiopathic recurrent miscarriage, recruited from all over the UK and as control, 18 women who had requested sterilization. Endometrial samples taken on about day 21 of the menstrual cycle.  29 of those found to have more than 5 per cent of NK cells at that point were given 20mg prednisolone orally per day for the first 21 days of each menstrual cycle, then another endometrial sample was taken.   The main results were that those with recurrent idiopathic miscarriage syndrome were significantly more likely to have high numbers of NK cells at day 21 of their menstrual cycle, and that the prednisolone reduced the median percentage from 14% to 9%.

However suggestive these results are, they remain tentative and controversial.  An attempt by E. Tuckerman,  S.M. Laird, A. Prackash and T.C. Li to predict miscarriages based on NK cell measurements failed.

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