Intravaginal misoprostol effective in evacuation

OB/GYN News, Dec 1, 2002 by Nancy Walsh

SEATTLE -- Misoprostol administered intravaginally is "highly effective" for uterine evacuation in women with failed first-trimester gestations, Dr. Jerry M. Gilles said at the annual meeting of the American Society for Reproductive Medicine.

In a randomized clinical trial conducted by the National Institute of Child Health and Human Development, an overall success rate of 80% was seen with the administration of one or two doses of the synthetic prostaglandin analogue.

Medical management following miscarriage can avoid the cost and complications of surgery as well as the uncertainties of expectant management, he said.

But reported evacuation rates with intravaginal misoprostol have ranged from 13% to 96%. "This wide range in evacuation rates may be due in part to variability in absorption of the drug, particularly when given intravaginally," said Dr. Gilles of the department of obstetrics and gynecology at the University of Miami.

The researchers also sought to determine if absorption of the drug could be improved by the addition of saline. Results of observational studies have suggested that when the vagina is cleansed and saline added to the vaginal tablet, absorption may be improved, leading to higher rates of evacuation success, Dr. Gilles said.

Eighty women with embryonic or fetal demise or anembryonic pregnancies with a crown-rump length less than 41 mm or a mean sac diameter less than 46 mm were randomized to receive 800 [micro]g of misoprostol alone or with 2 mL of saline added. There were 39 patients in the dry misoprostol group and 41 in the saline group, he said. Transvaginal pelvic ultrasounds were performed on days 3, 8, and 15. If the gestational sac was still present at day 3, a second dose of misoprostol was given, and if it remained by day 8, a D&C was performed.

By day 3, the sac had been expelled by 73% in the saline group and 64% in the dry misoprostol group. The cumulative expulsion rate by day 8, which included patients who received a second dose, was 83% in the saline group and 79% in the dry group.

By day 30, there were 34 patients in each group who had passed the sac and did not require a D&C. Five patients in each group underwent D&C, either for failure to expel the sac or for excessive bleeding. Two patients in the saline group were lost to follow-up and were classified as failures.

The success rates at day 30 were 83% in the saline group and 87% in the dry group. This difference was not statistically significant, he said. Three patients initially were classified as successful because of sac expulsion by day 30 but required later D&C because of persistent bleeding. "Even with these delayed failures, the overall success rate was around 80%," Dr. Gilles said.

There were no statistically significant differences in success rates between the two groups, leading Dr. Gilles to conclude that there was no benefit to adding saline to the misoprostol. "Administering the misoprostol as manufactured is more economical and less cumbersome," he said.

The frequency of side effects also was similar between the two groups, with an overall incidence of 97% for pain, 78% for headache, 71% for chills, and 40% for fever. Most patients described their pain as mild to moderate. Despite the high frequency of side effects, 79% of the women described the treatment as acceptable, he said, Most said they would undergo the same treatment again.

An audience member asked why some patients required a second dose of the medication. "It may be that there are variations between patients in the levels of modulators, such as progesterone and cytokines, that regulate prostaglandin receptor activity," Dr. Gilles said.