Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women

Abstract

We report the results of a large-scale trial with mifepristone (RU 486) followed by the administration of a prostaglandin (PG) analogue for the medical termination of early pregnancy. Altogether, 16,173 patients from 300 centers were evaluated. 48 women (0.3%) were lost to follow-up prior to, and 416 (2.6%) after the PG administration, and therefore the efficacy was evaluated in 15,709 women. Overall, the success rate was 95.3%, with no statistical difference regarding the nature and dose of PG used. The median duration of bleeding was 8 days, being 12 days or less in 89.7% of the women. Bleeding was significant enough to necessitate a vacuum aspiration or a dilatation and curettage in 0.8% of the cases. A blood transfusion was necessary in 0.1% of the women (11 patients). Serious cardio-vascular side-effects were reported in 4 cases after the PG (sulprostone) injection: they consisted of one acute myocardial infarction attributed to a coronary spasm, and in marked hypotension in the other 3 women. All patients recovered uneventfully. In conclusion, RU 486 followed by a PG analogue provides an efficient and safe medical alternative to surgery for early pregnancy termination, provided that the recommended protocol is adequately followed and the contraindications to prostaglandins are respected.

PIP: Between May 1988 and September 1989, physicians administered 600 mg of RU-486 followed by either 1 mg gemeprost vaginal pessary or im injection of 0.125-1.0 mg sulprostone to 16,369 11-48 year old women attending 30 centers in France to evaluate this regimen's safety and efficacy and whether trained prescribers could adequately comply with recommended protocol. 13.6% patients whose gestational age was greater than the recommended 50 days, underwent RU-486 and prostaglandin (PG) analogue administration. 78% of 571 patients did not receive a PG analogue because they expelled the conceptus after RU-486 administration. The remaining 126 women did not receive RU-486 even though they had not expelled the conceptus. Clinicians administered to PG analogue to 88.4% of all women within the recommended 36-48 hours after RU-486 administration. The RU-486 and PG analogue regimen had a success rate of 95.3%. Women who received the PG analogue within the recommended time period had a higher success rate than those who received it either too early or too late (95.8% vs. 92.8% and 93.9%, respectively; p = .001). In those women who did not receive the PG analogue, RU-486's success rate was considerably lower (88.6%; p .001). The nature and does of the PG analogue greatly influenced expulsion within 4 hours after its administration (44.1% after 1 mg gemeprost vs. 57.3%, 55.8%, 73.5%, and 67.6% after 0.125, 0.25, 0.375, and 0.5 mg sulprostone respectively; p .001). The higher doses of sulprostone had a significant effect on duration of bleeding (e.g., 9.1 days for 0.5 mg vs. 7.1 days for 0.125 mg p .001). 89.7% of the women bled for no more than 12 days. The bleeding was so profuse in 0.8% of the cases that either vacuum aspiration or dilatation and curettage was needed. 11 women required 1-3 units of blood. 8.5% experienced at least 1 side effect, the most common being uterine cramps (1.6% of all cases). 4 women suffered from grave cardiovascular effects (myocardial infarction in 1 case, severe hypotension in 3 cases). As long as prescribers consider contraindications and follow the protocol, this regimen is a viable alternative to surgical abortion.