and should assess relative pain, interval to fetal expulsion, blood loss, and frequency of infection, uterine perforation, and incomplete expulsion requiring surgical intervention.

CERVICAL RIPENING

It appears that antiprogestins not only sensitize the myometrium to subsequent prostaglandin installation but also help to ripen the cervix. This property may help to manage clinical situations such as (1) preparation for second-trimester abortion, (2) preparation for labor induction at term or post-term, and (3) preparation of the cervix when labor must be induced because of intrauterine fetal demise.

Animal studies have demonstrated that mifepristone matures and ripens the cervix, as measured by an increase in cervical diameter and decrease in cervical resistance to mechanical dilation (Ulmann and Silvestre, Appendix B6). This effect occurs through the molecular mechanisms that characterize the normal cervical-ripening process, including increase in water and hyaluronic acid content as well as collagenase activation. Several studies documenting the ability of antiprogestins to induce cervical maturation and ripening before vacuum aspiration have shown a significant effect 24 to 48 hours after mifepristone administration (Ulmann and Silvestre, Appendix B6). A dose-finding Canadian study using placebo or 100, 200, 400, or 600 mg of mifepristone as a single dose, administered 24 or 48 hours before cervical calibration, showed a significant increase in cervical diameter that was linearly related to dose up to 400 mg (Lefebvre et al., 1990). Patients treated with mifepristone had either an equivalent or a lower blood loss after vacuum aspiration than those treated with a placebo (Ulmann and Silvestre, Appendix B6). Thus, mifepristone in doses up to 600 mg appears to be efficacious in ripening and dilating the second-trimester cervix before D&E, as well as in decreasing treatment to expulsion time in nonsurgical protocols when used in conjunction with prostaglandin.

It should be noted that prostaglandin alone in an intravaginal formulation is approved by the Food and Drug Administration for the indication of cervical ripening. Studies will be needed to determine the relative efficacy of mifepristone.

Because of the discomfort associated with either elective termination of second-trimester pregnancy or the termination of the genetically abnormal or dead fetus, the ability of antiprogestins to shorten the therapeutic process is attractive. Overall, the antiprogestins in the second trimester are well tolerated, with the most frequently reported side effects being abdominal pain, nausea, and vomiting. All second-trimester pregnancy terminations carry the risk of bleeding and the



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