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.
PIP: Between June and October 1991 health workers administered 1 dose of 600 mg mifepristone (RU-486) and a single oral dose of 400 mcg misoprostol on day 3 to at least 488 women at 25 centers in France to terminate pregnancy of less than 50 days duration. Pregnancy termination occurred within 48 hours in 2.9% of all women. They had only received RU-486. 1% vomited after taking the first dose of misoprostol, necessitating a second dose. The overall success rate for this regimen was 96.9%. 12 hours was the mean time between taking misoprostol and expulsion of the conceptus. The median time was 3 hours. The types of failure were incomplete expulsion of the conceptus (1.8%), ongoing pregnancy (0.8%), and prolonged bleeding (0.4%). Mean duration of bleeding following the regimen was 9 days. A second study occurred between March 1991 and March 1992 among at least 385 women at 1 center in France. They received RU-486 and misoprostol in the same manner as the women in study 1, but those who did not experience pregnancy termination within 4 hours after the initial dose received another 200 mcg dose of misoprostol. 5/5% experienced pregnancy termination before administration of misoprostol. 69.1% experienced termination within 4 hours. Pregnancy termination occurred within the first 3 hours in almost 90% of them. 27 women who did not abort within 4 hours did not take the additional dose and 26 of them aborted completely. The sole woman with a continued pregnancy underwent vacuum aspiration. 67 of the 71 women who took the second dose completely expelled the conceptus within 48 hours. Thus, 79.2% of all women aborted while being monitored at the center. The overall success rate was 98.7% . The leading side effects in both studies in order of frequency were uterine cramps and nausea, vomiting, and diarrhea. These results showed that oral administration of misoprostol is as effective and well tolerated as other prostaglandins administered parenterally or vaginally.