Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review

Abstract

The availability of a medical mode of termination of early pregnancy by the administration of RU486, an antiprogesterone alone, or in combination with one of the PG analogues significantly reduces the maternal morbidity and mortality associated with the classical surgical abortion. RU486 given alone in early pregnancy induces complete abortion in 60% to 85% of cases, and when combined with prostaglandin analogues, gemeprost or sulprostone, reaches a success rate of 95% to 99%. RU486 may also be of potential value in the medical treatment of ectopic pregnancy. Its use as a postcoital contraception is suggested, but further research is required to determine whether RU486 can be used on a once-a-month basis for contraception.

PIP: This review of trials of RU-486 with prostaglandin for termination of early pregnancy begins with a summary of experimental and conventional early abortion techniques, introduces RU-486 with explanations of its mechanism of action, pharmacology, effects on adrenocortical receptors, the hypothalamic axis, and endometrium and ends with a discussion of its use in ectopic pregnancy and post-coital contraception. RU-486 acts by stabilizing the progesterone receptor so it cannot signal its DNA site to effect hormone action. Its peak plasma level is achieved in 2 hours, with a half life of 20 hours. RU-486 has anti-glucocorticoid effects at high doses. It also inhibits gonadotropin secretion in a dose-dependent manner, blocking ovulation. The main use of RU=-486 is in early pregnancy termination, a procedure termed contragestion, a consequence of its anti-progesterone action on the endometrium. Given alone, it is effective only 60-73% of pregnant women. Supplemented with an injection of Sulprostone, or a vaginal suppository of Gemeprost, both prostaglandin analogs, RU-486 typically will induce abortion in 96% of women up to 7 weeks pregnant. The abortion interval depends of prostaglandin dose. About 1% of women fail to abort, about 2% are incomplete, and 1% require treatment for hemorrhage, in a French trial of 2115 women. RU-486 has been used to manage ectopic pregnancy in preliminary studies. It is also being investigated as a postcoital agent, and appears to be effective from midcycle through the premenstrual phase, a wider window than current medical methods.