The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.

BACKGROUND AND METHODS:The combination of mifepristone (RU 486) and a prostaglandin analogue given either intramuscularly or intravaginally is effective in terminating early pregnancy, but the prostaglandin component of the regimen is cumbersome to administer and has side effects. We conducted two studies to determine the efficacy of 600 mg of mifepristone followed by a small dose of misoprostol, an orally active prostaglandin E1 analogue, for the same purpose. In the first study, 505 women who had had amenorrhea for less than 50 days received 400 micrograms of misoprostol 48 hours after receiving mifepristone, if the pregnancy was not terminated within that period. In the second study, 390 women initially received the same treatment, but if the pregnancy was not terminated within four hours after the administration of misoprostol, they were offered an additional 200-micrograms dose of misoprostol. RESULTS:In study 1, the rate of success (termination of pregnancy and complete expulsion of the conceptus) was 96.9 percent (95 percent confidence interval, 94.1 to 97.7 percent)--similar to the success rate of approximately 95 percent for mifepristone followed by the intramuscular or intravaginal administration of prostaglandin. Abortion occurred in 2.9 percent of the women within 48 hours after the administration of mifepristone, in 60.9 percent within 4 hours after the administration of misoprostol, and in 33.2 percent thereafter. The failures included ongoing pregnancies in four women (0.8 percent) and incomplete abortions in nine (1.8 percent); two other women (0.4 percent) required vacuum aspiration for prolonged uterine bleeding. In study 2, pregnancy was terminated in 5.5 percent of the women before the administration of misoprostol and within four hours after the first dose of misoprostol in 69.1 percent. Among the 71 women who received a second dose of misoprostol, 67 had complete abortions, 2 had partial retention of the conceptus, 1 had synechia with ongoing pregnancy, and 1 had an ectopic pregnancy. One ongoing pregnancy, which was terminated by vacuum aspiration, was recorded among the 27 women who declined to take the second dose of misoprostol. The overall rate of success of the regimen with the optional second dose of misoprostol was 98.7 percent (95 percent confidence interval, 96.8 to 99.5 percent). No woman had any serious adverse event. CONCLUSIONS:The combination of mifepristone and misoprostol is effective for the termination of early pregnancy in terms of success, tolerance, safety, and practicality.

The most used medical method for early pregnancy interruption associates the antiprogestin RU486 (Mifepristone) and an intramuscularly injected prostaglandin (Sulprostone) (Silvestre et al., New Engl. J. Med., 322, 1990, pp. 645-648). Misoprostol, an orally active PGE1 synthetic derivative, showed the same efficacy as Sulprostone in a trial including 100 patients. The medical characteristics and potential of the new method are briefly discussed.

The most used medical method for early pregnancy interruption associates the antiprogestin RU486 (Mifepristone) and an intramuscularly injected prostaglandin (Sulprostone) (Silvestre et al., New Engl. J. Med., 322, 1990, pp. 645-648). Misoprostol, an orally active PGE1 synthetic derivative, showed the same efficacy as Sulprostone in a trial including 100 patients. The medical characteristics and potential of the new method are briefly discussed.

The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl l)-17 alpha-(prop-1-ynyl) estra-4,9-dien-3-one), orally administered once (600 mg), is an efficient contragestive agent in approximately 80% of pregnant women who have been amenorrheic for up to 41 days. Later on, its use is not recommended since after 41 day of amenorrhea there is an increase in the number of incomplete expulsions. A vaginal suppository of 1 mg Gemeprost, a synthetic PG-E1 analogue, has been prescribed 36-48 hrs. after the administration of RU 486. Such a suppository cannot provoke the interruption of the pregnancy by itself. In 106 women seeking for the interruption of pregnancy, and who were amenorrheic for 49 days or less, RU 486 plus prostaglandin association led to the interruption of pregnancy in all cases, and no further instrumental intervention was required. This preliminary report suggests that this method is an efficient alternative to conventional techniques available presently.