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Clinical Applications of Mifepristone (RU486) and Other Antiprogestins: Assessing the Science and Recommending a Research Agenda (1993)
Institute of Medicine (IOM)

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. "B1. 1993: RU 486--A Decade on Today and Tomorrow." Clinical Applications of Mifepristone (RU486) and Other Antiprogestins: Assessing the Science and Recommending a Research Agenda. Washington, DC: The National Academies Press, 1993.

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Clinical Applications of Mifepristone (RU 486) and other Antiprogestins: Assessing the Science and Recommending a Research Agenda

decrease of a2-adrenoreceptors (Kovacs and Falkay, 1993). A dose of 200–600 mg of RU 486 decreases the force required to dilate the cervix and has significantly fewer side effects than gemeprost (vaginal pessary). It also compares favorably with mechanical dilators such as Lamicel or Dilapan (Cohn and Stewart, 1991; Henshaw and Templeton, 1991; Gupta and Johnson, 1992; Thong and Baird, 1992).

In therapeutic second- and third-trimester abortions, RU 486 is most often used before the administration of prostaglandin, so that the dose of prostaglandins can be decreased, while pain and other side effects are reduced and expulsion is accelerated (Rodger and Baird, 1990). RU 486 also decreases the waiting time, and thus the pain and psychological suffering, in cases of a fetal demise (Cabrol et al., 1985).

Initiation of Labor

A decrease of progesterone activity occurs during parturition, but its precise role in successful delivery is unclear, particularly in primates (including humans) where it does not seem to be the primary event. In rats, RU 486 can synchronize delivery (Bosc et al., 1985), and in cattle (Li et al., 1991a,b) it is very efficient in facilitating parturition. In rhesus macaques near term, RU 486 provokes changes of prostaglandins and of the cervical status, but these modifications do not follow the same orderly sequence as those found during spontaneous delivery (Haluska et al., 1987; Wolf et al., 1993). It is not known if RU 486 increases gap junctions between myometrial cells in women as it does in rats (Garfield et al., 1987), but ß2-adrenoreceptor levels are unchanged in the myometrium (El Alj et al., 1989).

RU 486 has been tested in women at term who require labor induction for various medical indications such as post-term pregnancy and preeclampsia. When compared to placebo controls, the number of spontaneous deliveries is significantly increased; the amount of oxytocin, if required, is much lower; and the time to induce labor is shortened by RU 486 (Frydman et al., 1992). No undesirable incident, in mothers and newborns, was observed with the dose used (two times, 200 mg each), similar to observations made in monkey studies (Wolf, 1989b).

In summary, RU 486 appears to be safe for inducing labor when continuation of pregnancy is a risk for the fetus, the mother, or both. Systematic studies should now follow the development of babies born after RU 486 treatment, since it is known that in primates, RU 486 passes from mother to fetus during pregnancy (Wolf et al., 1988). The effects of neonatal and even embryonic (Wolf et al., 1990) exposure need to be assessed carefully (Weinstein et al., 1991). Until the absolute safety of antiprogestins is demonstrated in cases where there is a medical indication for labor induction, its use for convenience should be forbidden.

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