A regimen of medical abortion consisting of 200 mg of mifepristone and 400 mcg of misoprostol is as likely to successfully terminate an early pregnancy as a regimen using the same dosage of misoprostol and 600 mg of mifepristone. In a study of treatment effectiveness conducted at 17 centers worldwide, 89% of women treated with the lower dose of mifepristone and 88% of those treated with the higher dose of the drug had a complete abortion.¹ The proportion of women in each group who experienced side effects such as lower abdominal pain, nausea, vomiting and diarrhea was similar. The success of both of the regimens was related to gestational age: The risk of a continuing pregnancy was more than twice as high among women who received treatment 4-5 weeks after the expected date of menses as it was among those who were treated no more than 15 days after they missed their menstrual period.

Women were eligible to enroll in the study if they had positive pregnancy test results, were in good health, had a history of regular menstrual periods and were no more than 35 days past the expected date of their menses; gestational age was confirmed through a pelvic exam. Exclusion criteria included medical conditions that would contraindicate use of either of the drugs in the treatment regimen, and a history of thromboembolism, liver disease or pruritus of pregnancy (an inflammatory skin condition characterized by severe itching). In addition, women could not participate in the study if they were heavy smokers (defined as having smoked 10 or more cigarettes per day over the prior two years), were using an IUD, were breastfeeding or had a known or suspected ectopic pregnancy.

A total of 1,589 women were randomly assigned to one of two treatment regimens. One group of women was treated with a single oral dose of 600 mg of mifepristone, followed 48 hours later by a 400 mcg oral dose of the prostaglandin misoprostol. Women in the second group received 200 mg of mifepristone, also followed by 400 mcg of misoprostol. The women's vital signs and any side effects of the drug were assessed hourly for three hours after the administration of misoprostol. All women were asked to maintain a diary of side effects (e.g., nausea, vomiting, diarrhea and lower abdominal pain) and to note any days of bleeding during the study period. Study participants were evaluated 15 days and 43 days after beginning treatment.

The mean age of the women in the sample was 27, and approximately two-thirds had ever given birth. At enrollment, the study participants were an average of 19 days past the expected date of menstrual onset. The two treatment groups did not differ significantly on any of these baseline characteristics.

Eighty-nine percent of women who received the 200 mg dose of mifepristone and 88% of those who received the 600 mg dose had a complete abortion without surgical intervention. When the data were reanalyzed to omit 41 cases in which the treatment regimen was not completed properly or the outcome was unknown, the success of the two regimens increased to 92% and 91%, respectively. Some 3% of patients who took the lower dose of mifepristone and 5% of those who took the higher dose had incomplete abortions and required curettage. Three percent of women who received the 200 mg treatment and 2% of those who received the 600 mg treatment had a continuing pregnancy. In about 2% of cases in each group, no cardiac activity was present after treatment, but the gestational sac was not expelled.

Regardless of mifepristone dosage, the likelihood of treatment failure rose with increasing delay in menses (p<.01). Overall, the failure rate was 8% among women with a menstrual delay of no more than 14 days, 11% among those with a delay of 15-21 days and 13% among those with a delay of 22-28 days; that rate rose to 20% among women with a menstrual delay of 29 days or more.

Compared with women who had a menstrual delay of fewer than 15 days, women who had a menstrual delay of 22-28 days or 29 days or more had odds of abortion failure more than twice as high (2.2-2.3) after the effects of treatment center were accounted for.* In addition, the proportion of women with a continuing pregnancy after treatment increased significantly with the length of the delay (p<.01), from fewer than 2% among women with a delay of no more than 21 days and 3% among those with a delay of 22-28 days to 9% among those with a delay of 29-35 days.

The dose of mifepristone was not related to the occurrence of side effects. More than 80% of women receiving either dosage regimen reported experiencing lower abdominal pain at some point during treatment, and more than 65% reported experiencing nausea. Nearly 30% of the women in each group reported vomiting, and about 10% reported diarrhea. However, five women who took the higher dose of mifepristone needed a blood transfusion, compared with none of those who took the lower dose of the drug (p=.03).

The researchers conclude that although a 200 mg dose of mifepristone, in combination with a 400 mcg dose of misoprostol, constitutes an effective regimen for medical termination of pregnancy within the first three weeks after a missed menstrual period, "the efficacy of this oral regimen among women with a menstrual delay of more than 21 days was too low to justify [its use] in such pregnancies." --K. Mahler

REFERENCE

1. World Health Organization Task Force on Post-Ovulatory Methods