In recent years, there has been recognition that if the cervix is unfavorable, labor will rarely progress successfully to a vaginal delivery. Bishop attempted to define parameters of successful or failed labor induction with a cervical scoring system. Successful outcomes of cervical ripening include vaginal delivery without prolonged labor times, no increase in infection rates and good neonatal outcomes. Although the Bishop score is widely accepted, and it is agreed that progressive cervical dilatation will rarely occur unless softening and distensibility occur first, the task of “motivating” the cervix to achieve an optimal Bishop score has been challenging and frustrating.

What is the most optimal cervical ripening agent? The safety profile, efficacy and cost should figure into the decision analysis as each agent is compared in a randomized, controlled study. Although an effective labor-inducing agent, oxytocin (Pitocin) has not proved to be the best cervical ripening agent. Mechanical devices, various prostaglandin preparations, and local application of estrogen and relaxin are currently vying to be the cervical ripening agent of choice.

Prostaglandin E₂ (PGE₂) analogs have been widely studied. The only currently available PGE₂ analog labeled by the U.S. Food and Drug Administration (FDA) for use in cervical ripening is dinoprostone, marketed as a gel (Prepidil) for intracervical administration and as a timed-release vaginal insert (Cervidil). Despite widespread use of dinoprostone, randomized trials have failed to validate that its use results in a reduced cesarean section rate despite its benefits as a cervical ripening agent.¹

However, there is a better and less costly cervical ripening agent available, although the FDA has not yet labeled it. Misoprostol (Cytotec), an E₁ prostaglandin, has been labeled for the treatment and prevention of gastric ulcer disease associated with the use of nonsteroidal anti-inflammatory agents, but it has not been labeled for use in obstetric applications. The efficacy, safety and cost-effectiveness of misoprostol for cervical ripening and labor induction have been validated by numerous randomized, controlled trials. Compared with intracervical PGE₂ gel, vaginal misoprostol has shown efficacy in reducing time to delivery and increasing the probability that vaginal delivery will occur within 24 hours of initiation of the drug without need for oxytocin augmentation.² Misoprostol has also been shown to be an effective alternative to oxytocin infusion for labor induction in women with premature rupture of the membranes at term.³

A meta-analysis⁴ of eight randomized trials assessing the safety and efficacy of misoprostol for cervical ripening and labor induction in 966 women (488 of whom received misoprostol and 478 of whom served as control subjects) confirmed the impact of its use. All of the patients in the control groups received PGE₂ or oxytocin, with the exception of one trial in which patients were given placebo. The dosage of misoprostol varied from 25 μg every two hours to 100 μg as a single dose. Six trials included use of continuous fetal electronic monitoring and tocodynamometry.

Compared with patients in the control groups in these studies,⁴ patients receiving misoprostol had lower cesarean section rates as well as shorter durations of labor and reduced need for oxytocin augmentation. No differences were noted in the incidence of low five-minute Apgar scores and neonatal intensive care admissions. Although the rate of tachysystole was two times higher in the groups receiving misoprostol, compared with the control groups, the difference was not statistically significant. There have been no documented studies validating that tachysystole with use of misoprostol results in adverse outcomes in mother or fetus. Although meta-analyses provide evidence of statistical differences in the effectiveness of various drugs, they do not replace the results of a large randomized trial.⁴ Large studies are currently under way in several institutions.

Using off-label drugs in obstetrics such as those used to arrest preterm labor is not uncommon. Clinicians must be aware of the pitfalls when these drugs are used. Just because a drug is used for an off-label indication does not imply that it is experimental and that sufficient studies have not been conducted. Wing and Paul,⁵ authors of numerous articles on cervical ripening agents, have suggested guidelines for the use of misoprostol. Hospital protocols should be formulated and adherence to inclusion and exclusion criteria, and surveillance of outcomes should be strictly encouraged. Informed consent should be obtained after the options for cervical ripening and labor induction are discussed. A note should be written stating that the risks and benefits of the drug have been explained and that consent has been given to use it for a particular situation.

The authors stress that it is extremely important for the 100 μg tablet of misoprostol to be carefully cut into quarters by the pharmacist to ensure correct dosing.⁵ A 25-μg dose every four hours appears to be the optimal dosage to induce labor and avoid adverse events. The quartered tablet is placed directly into the posterior vaginal fornix, preferably without the use of lubricant, which can interfere with absorption and dissolution of the tablet. The authors' protocol does not recommend misoprostol use for longer than 24 hours. If oxytocin augmentation is required, it should be given no sooner than two hours after the last dose of intravaginal misoprostol.

The authors' guidelines for redosing misoprostol state that it should be withheld if two or more contractions occur in 10 minutes, a Bishop score of 8 has been achieved, active labor begins or the fetal heart rate pattern is nonreassuring.⁵ If uterine tachysystole (defined as six or more contractions in a 10-minute window for two consecutive 10-minute windows) occurs, 0.25 mg of terbutaline (Bricanyl) should be administered subcutaneously.

Wing and Paul⁵ have laid out a reasonable protocol that maximizes the effectiveness of misoprostol while minimizing adverse events. Physicians electing to use misoprostol for labor induction and cervical ripening should follow published guidelines and should be able to confidently manage adverse events.