potential need for surgical intervention. The use of antiprogestins given 36 to 48 hours before either a surgical procedure or prostaglandin installation appears to be well tolerated without the addition of significant clinical complications.
Recent advances in molecular biology and genetic, karyotypic diagnosis, as well as our increased ability to diagnose early structural abnormalities with ultrasonography, will inevitably increase the number of abnormal second-trimester gestations identified. The emotional stress of terminating such a pregnancy is great, as is the case of fetal demise, and therapeutic modalities to reduce both the time necessary for such a procedure and the discomfort involved merit further investigation.
In addition to its possible use in cervical ripening in preparation for labor induction, mifepristone may also be useful in inducing labor, for instance in cases of intrauterine fetal demise and during late pregnancy when the medical complications require prompt delivery.
Fetal demise is an unfortunate occurrence in both second- and third-trimester pregnancies, and requires evacuation of the uterus. Studies have evaluated mifepristone's ability to initiate labor in cases of fetal demise. In the study of Cabrol et al. (1990), 600 mg of mifepristone, given on two consecutive days after diagnosis of fetal death, caused the initiation of labor within 72 hours in 63 percent of women, compared to spontaneous initiation of labor in 17 percent of the placebo-treated women. Thus, it appears that mifepristone alone is able to induce labor in patients with intrauterine fetal demise and that expulsion takes place significantly earlier than in placebo-treated patients.
Studies in ewes and monkeys have indicated that, at term, antiprogestins induce uterine contractions and enhance the myometrial sensitivity to oxytocin. Newborn monkeys of mothers treated with antiprogestins were normal and, in fact, grew more rapidly than did newborns from untreated mothers (Wolff et al., 1989). This is thought to be an effect of increased milk output in primate mothers treated with antiprogestins and is believed to be secondary to abrogation of the suppressive effect of progesterone on prolactin secretion. An initial study in humans by Frydman et al. (1992) evaluated the efficacy and safety of mifepristone for induction of labor in post-term pregnancies or in term pregnancies when other medical indications for labor induction were present. This placebo-controlled study used 200 mg of mifepristone daily for two consecutive days and showed a marked increase in the number of