inhibitory effect of progesterone. Treatment with mifepristone changes the inactive uterus to an active one. The time interval between the start of mifepristone treatment and the appearance of uterine contractions is 24 to 36 hours. Simultaneous with increased contractility, the sensitivity to prostaglandin increases about five times (Swahn and Bygdeman, 1988). These data created the scientific background for combining mifepristone and a low dose of prostaglandin for termination of early pregnancy.

Mifepristone also has a ripening effect on the cervix and causes dilatation of the cervical canal (Rådestad et al., 1990; WHO, 1990). These effects do not seem to be mediated through a stimulation of endogenous prostaglandin production because they are not blocked by simultaneous treatment with prostaglandin biosynthesis inhibitors (Rådestad and Bygdeman, 1992). It is possible, however, that the antiprogestin acts by inhibiting or changing prostaglandin metabolism.

TERMINATION OF EARLY PREGNANCY
Mifepristone Alone

Clinical evidence that it was possible to interrupt early human pregnancy with mifepristone was first provided by Hermann et al. (1982) and was confirmed shortly afterwards in a dose-finding study conducted under the auspices of the World Health Organization (Kovacs et al., 1984). Although carried out in a relatively small number of women, these two studies permitted several tentative conclusions that were proven in subsequent trials. Undoubtedly, the most disconcerting findings were the relatively low efficacy, 73 percent and 61 percent, respectively, and the absence of a clear dose-response relationship. Efforts to improve the therapeutic efficacy were made by various investigators and focused on changing the daily dose and the duration of treatment (for references, see Van Look and Bygdeman, 1989). From these studies, two conclusions could be drawn. Firstly, the frequency of complete abortion decreased with advancing pregnancy, and secondly, there was no relationship between the success rate and the treatment regimen employed for women at the same stage of gestation. For pregnancies up to eight weeks the frequency of complete abortion was generally between 60 percent and 70 percent. A somewhat higher success rate could be achieved if treatment was given within the first 10 to 14 days after the missed menstrual period. For example, Couzinet et al. (1986) reported a complete abortion rate of 85 percent following treatment with up to 800 mg mifepristone for 2 to 4 days in women who were within 10 days of missed menses.



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