Clinical studies with the antiprogesterone Mifepristone (RU486) in human pregnancy termination
Mifepristone in combination with prostaglandin was given to 135 women requesting legal termination, with up to 63 days of amenorrhoea. Various dosage regimes were employed. A 600mg dose of Mifepristone followed forty eight hours later by a prostaglandin vaginal pessary was as effective as more complex regimes given over a longer period. Complete abortion rates of greater than 90% were achieved (approaching the efficacy of the surgical alternative). The outcome of treatment was not gestation dependent. Treatment was well tolerated, acceptable to women, and associated with a low incidence of psychological morbidity. The only serious complication encountered was a 2.5% incidence of heavy bleeding requiring blood transfusion and emergency curettage. Mifepristone is also a useful cervical priming agent prior to late first trimester surgical termination. In a double blind placebo controlled study, forty women received either placebo or 600mg Mifepristone forty eight hours prior to surgery. In the treated group significant cervical dilatation was induced and significantly less force was required to dilate the cervix to allow the passage of a number 8 Karman curette. Blood loss was also significantly reduced. The treatment was well tolerated by patients. No serious complications were noted. In the second trimester, Mifepristone was given at various time intervals prior to prostaglandin induced abortion. The induction to abortion interval and doses of prostglandin required was significantly reduced in Mifepristone treated patients. There was no apparent advantage in an exposure time to Mifepristone of longer than twenty four hours. Serum hormone changes and the development of uterine activity and increased sensitivity to prostaglandins (as measured by intrauterine pressure recordings) after Mifepristone administration are presented. The results are discussed and incorporated into our understanding of the mechanisms of action of Mifepristone in human pregnancy termination.