Cervical ripening with mifepristone before labor induction: a randomized study

doi:10.1016/S0029-7844(98)00225-7

Obstetrics & Gynecology

Volume 92, Issue 4, Part 1, October 1998, Pages 487-492

https://doi.org/10.1016/S0029-7844(98)00225-7 Get rights and content

Abstract

Objective: To determine the efficacy and safety of mifepristone for cervical ripening in post-term pregnancies.

Methods: Women with post-term pregnancies and Bishop scores less than 6 were assigned randomly to mifepristone (41 patients) or placebo (42 patients). Mifepristone was given orally in a dose of 400 mg. Efficacy was assessed by change in the Bishop score within 48 hours after treatment; a score of 6 or greater was considered a “strict” success. An “extended” success rate was defined, including all patients with scores of at least 6 or those who delivered within 48 hours of treatment. Antenatal safety was assessed by fetal heart rate testing before and throughout labor. Neonatal safety was assessed by Apgar score, arterial or venous pH of cord blood, and blood glucose level during the first 48 hours. Analysis used Student t test for continuous variables, Kruskal-Wallis test for ordinal data, and χ² for categoric variables.

Results: Strict success was achieved in 10 of 18 mifepristone patients (55%) evaluated for Bishop score on day 2 versus 8 of 29 placebo patients (27.5%) (P = .004). Extended success was achieved in 33 mifepristone patients (80.5%) and 21 placebo patients (50.0%) (P = .004). There were no statistical differences with regard to number of cesareans or fetal and neonatal safety.

Conclusion: Mifepristone proved effective for cervical ripening and reduced the time to delivery compared with placebo, but it did not improve the rate of cesarean. Our study did not include enough pregnancies to reach conclusions about fetal or neonatal safety.

Section snippets

Subjects and methods

From January 1991 to February 1992, this randomized, double-blind, placebo-controlled study was conducted in two centers, Montpellier University Hospital and Nantes University Hospital, France. The protocol was approved by the institutional ethics committee, and all patients gave informed written consent before inclusion. The patients were women who required labor induction for post-term pregnancies (gestational age at least 41 weeks + 3 days). Subjects eligible for inclusion were those with

Results

There were no statistical differences (mean ± standard deviation [SD]) between the mifepristone and placebo groups with regard to maternal age (28.5 ± 4.3 and 28.3 ± 5.0 years, respectively) or gestational age at delivery (41.5 ± 0.2 and 41.6 ± 0.2 weeks, respectively). In each group, 20 patients were nulliparas and none had previous cesareans. The distribution of pregnancies and deliveries did not differ significantly between the groups. The median Bishop score was 3 (range 1–5) in each group.

Discussion

This study demonstrated significant efficacy of mifepristone for cervical ripening and induction of spontaneous labor within 48 hours after drug administration. Our findings are consistent with the results observed by Frydman et al,7 although they used a different protocol. They administered 200 mg of mifepristone daily for 2 days instead of 400 mg in a single dose, and induction of labor was scheduled at 72 hours instead of 48 hours. In addition, the inclusion criteria in their study7 were

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Cited by (39)

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis
2024, American Journal of Obstetrics and Gynecology
Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting.
With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020.
We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening.
We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation.
We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 μg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9).
When balancing efficacy and safety, vaginal misoprostol 25 μg represents the best method for outpatient cervical ripening.
Outcomes of mifepristone usage for cervical ripening and induction of labour in full-term pregnancy. Randomized controlled trial
2017, European Journal of Obstetrics and Gynecology and Reproductive Biology
The most commonly used approved indications for mifepristone in obstetrics include: termination of early pregnancy, cervical dilatation prior to abortion, labour induction in case of fetal death in utero. Fewer studies have been conducted on the effect of mifepristone on cervical ripening and induction of labour in term pregnancy with a live fetus. The aim of our study was to evaluate efficacy and safety of mifepristone use for cervical ripening and induction of labour versus expectant management in full-term pregnancy.
Randomized controlled trial. 149 women were randomized, 74 for cervical ripening and induction with mifepristone (200 mg orally at the moment of enrollment and, if applicable, second dose after 24 h), 75 – expectant management. Primary outcomes: gain in Bishop Score within 24 and 48-h of mifepristone; number of women going into spontaneous labor within 24, 48 and 72-h of mifepristone; rate of failed induction or expectant management. Secondary outcomes: enrollment-induction to delivery interval; mode of delivery; requirement of oxytocin augmentation, neonatal outcomes.
After 48 h from enrollment mean gain in Bishop score was 2.58 ± 1.33 in the induction group and 1.15 ± 0.97 in the expectant group (<0.001). Failed management rate was 5.41% and 2.67%, respectively. Significantly more mifepristone treated women had labour within 24, 48 and 72 h from enrollment (RR 15.20 CI 95% 2.06–112.18; RR 6.08 CI 95% 2.73–13.57; RR 2.14 CI 95% 1.04–4.42) (p < 0.05). Enrollment-induction to delivery interval was significantly shorter in mifepristone group: 2.69 ± 2.06 vs 3.77 ± 1.86 days (p < 0.001). Premature rupture of membranes, meconium-stained amniotic fluid were more common in expectant management, but regional analgesia and cephalopelvic disproportion – in induction group. There were no differences in mode of delivery, requirement of oxytocin augmentation and main neonatal outcomes.
Mifepristone was efficient on inducing cervical ripening and labour in full-term pregnancy. There were no significant difference in main maternal and neonatal outcomes between mifepristone use and expectant management. There were no serious adverse side effects of mifepristone, but there were some features of the course of labor, like more painful uterine contractions and trend of higher rate of cephalopelvic disproportion, that might be directly related to the mifepristone action.
Abnormal Labor and Induction of Labor
2016, Obstetrics: Normal and Problem Pregnancies
Mifepristone and misoprostol in the induction of labor at term
2007, International Journal of Gynecology and Obstetrics
Citation Excerpt :
Therefore, it seems likely that in most of the 66% of women who went into labor after mifepristone alone, the effects of the drug had a significant role to play. In 3 previous studies [6–8] mifepristone has been shown to be effective in initiating spontaneous labor or successfully ripening the cervix in 64%, 77%, and 80.5% of women, respectively, compared with placebo. The dose of mifepristone used varied from 50 mg, to 2 doses of 200 mg every 24 h, to 600 mg.
To assess the ability of mifepristone to prime the cervix adequately and induce labor in pregnant women at term; and when mifepristone alone proves insufficient, to determine whether oral misoprostol taken 48 h following mifepristone administration is effective in inducing labor.
In this prospective study 50 pregnant women at term with an unfavorable cervix were given 400 mg of mifepristone orally and allowed to return home. If labor did not start within 48 h, the women were admitted and induction was continued with 50 μg of misoprostol, a prostaglandin (PG) E1 analogue, taken orally every 4 h. The 50 controls, who were matched prospectively for parity and pregnancy duration, underwent labor induction according to the routine administration of 3-mg tablets of PGE2 vaginally.
In the study group, 66% of the women entered labor spontaneously or had a sufficiently ripened cervix within 48 h of taking mifepristone. However, there was no difference in time between prostaglandin administration and delivery between the control group and the 34% of women who required misoprostol in the study group. In the study group, the cesarean section rate was significantly lower among the women whose labor was induced with mifepristone alone than among those who required misoprostol. There were no differences overall in obstetric or neonatal outcomes between the study and control groups.
In this pilot sample, 400 mg of mifepristone was effective in inducing cervical changes and labor. Although there were no adverse effects using oral misoprostol in combination with mifepristone, labor was more difficult to induce in the women who did not respond to mifepristone alone, and these women had a higher operative delivery rate.
A randomized comparison of oral mifepristone to intravenous oxytocin for labor induction in women with prelabor rupture of membranes beyond 36 weeks' gestation
2005, American Journal of Obstetrics and Gynecology
Citation Excerpt :
The lack of efficacy of mifepristone as an initiator of labor in this study may be due to its theorized method of action, ie, that we allowed inadequate time for mifepristone to trigger a decline in the systemic level of progesterone or decrease in the local actions of progesterone on myometrium. Other researchers have allowed pretreatment periods of 24 to 96 hours after mifepristone but in women with intact membranes.19,20,22 Our results with 18 hours of pretreatment are similar to those previously reported: for example, Frydman et al19 reported that only 3% of women went into labor within 24 hours of receiving 200 mg mifepristone.
This study was undertaken to compare the use of oral mifepristone with intravenous oxytocin for labor induction in women with prelabor rupture of membranes (PROM) at 36 weeks' or greater gestational age.
Sixty-five women with spontaneous PROM were randomly assigned to receive orally administered mifepristone or oxytocin infusion. Two hundred milligrams of mifepristone was administered, and subjects were observed for 18 hours, or intravenous oxytocin was administered.
Thirty-three women received mifepristone and 32 received oxytocin. The average interval from start of induction to delivery was 1194.1 ± 568.7 minutes for mifepristone-treated subjects and 770.8 ± 519.9 minutes for oxytocin-treated subjects (P = .001, log-transformed data). Of 33 mifepristone-treated subjects and 32 oxytocin-treated subjects, 25 (78.1%) and 17 (51.5%), respectively, achieved successful induction (defined as vaginal delivery within 24 hours) (relative risk [RR] 0.66, 95% CI 0.45-0.96, P = .01). There was more fetal distress in the mifepristone-treated group (9 vs 2, RR 4.36, 95% CI 1.02-18.66, P = .02), and a trend toward more cesarean births (7 vs 3, RR 2.26, 95% CI 0.64-7.99, P = .19). Eleven infants of mifepristone-treated women (33.3%) and 3 infants of oxytocin-treated women (9.4%) were admitted to the neonatal intensive care unit (RR 3.56, 95% CI 1.09-11.58, P = .02).
Oral mifepristone administration 18 hours before oxytocin infusion did not improve labor stimulation in women with PROM near term, and was associated with more adverse fetal outcomes.
Use of mifepristone to ripen the cervix and induce labor in term pregnancies
2005, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Mifepristone was no more effective than placebo, regardless of the dose (50 to 600 mg). Our finding thus conflicts with previous studies showing a significant effect of mifepristone.17-23 Interestingly, we found that labor was prolonged in the 400 mg and 600 mg mifepristone groups.
This study was undertaken to determine the efficacy of mifepristone for ripening the cervix and inducing labor in term pregnancies.
In a double-blind placebo-controlled dose-finding study, 346 women received 50, 100, 200, 400, or 600 mg of mifepristone or placebo. The main endpoint for efficacy was the number of patients in whom labor occurred between 12 and 45 and 54 hours after treatment or who had a Bishop score 6 or greater. Maternal and fetal tolerability was also studied.
No significant efficacy was observed whatever the dose of mifepristone. Mifepristone was well tolerated by the mother and fetus.
Mifepristone, at doses up to 600 mg, does not induce labor within 54 hours in patients with unfavourable cervical status.

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Original ArticlesCervical ripening with mifepristone before labor induction: a randomized study

Abstract

Section snippets

Subjects and methods

Results

Discussion

Am J Obstet Gynecol

Am J Obstet Gynecol

Endocervical prostaglandin E2 gel for preinduction cervical ripeningClinical trial results

J Reprod Med

Termination of early pregnancy by the progesterone antagonist RU 486 (mifepristone)

N Engl J Med

Mifepristone (RU 486) for cervical priming prior to surgically induced abortion in the late first trimester

Contraception

Original Articles
Cervical ripening with mifepristone before labor induction: a randomized study

Endocervical prostaglandin E₂ gel for preinduction cervical ripeningClinical trial results