A Summary of Articles Published in English about Misoprostol (Cytotec) for Cervical Ripening or Induction of Labor

A note from the editor, Ina May Gaskin, CPM: This summary includes all those articles which I was able to obtain for review. It will be updated as others are published or become available to me.

For those readers who are curious as to what the medical literature in English has published about the use of the drug misoprostol (brand name: Cytotec) for cervical ripening or induction, I offer the following brief summary of the articles I was able to obtain. For your convenience, I have listed these articles in chronological order of their publication.

Definitions to keep in mind:

Tachsystole (polysystole) – Abnormally frequent contractions, more than 5 per 10 minutes.

Hypertonus – A contraction with a duration of more than 90 seconds.

Exaggerated uterine response – Hypertonic or tachysystolic contractions.

Hyperstimulation – Exaggerated uterine response with late fetal heart rate decelerations or fetal tachycardia (more than 160 beats per minute).

1. Margulies M et al. Misoprostol to induce labor [letter], Lancet 339 (1992):64.

This letter is the first mention in English of the use of misoprostol to induce labor. Its Argentinean authors mention two studies published in 1991 in Spanish “that corroborate the efficacy of vaginal misoprostol in inducing uterine contractions during the third trimester of pregnancy,” using an initial dose of 50 micrograms in the posterior vaginal fornix, followed by increasing doses of 50 micrograms every 2 hours until the desired level of uterine activity is reached or a maximum of 600 micrograms of the drug is reached.

We are not told the number of participants in the first study, nor are we told anything about the group with which the misoprostol group was compared. We are told that more than half of the women in the misoprostol group responded to a single 100-microgram dose of the drug.

The authors do tell us there were 64 women in the second study they mention in their letter to Lancet. Slightly more than half were given misoprostol, while the rest were given intravenous oxytocin.

Findings: “Side effects were not observed, but polysystole (more than 5 contractions in 10 min.) was more frequent in the misoprostol group (17%) than in the oxytocin group (12%); however, no fetal distress was associated with this condition in either group.”

However, this last statement appears in contradiction to another statement appearing in their letter. The sentence: “In the misoprostol group, induction was successful in 26 (79%) patients; 1 patient was delivered by caesarean section because of fetal distress.” [My italics] No explanation is given for this discrepancy.

Three women in the oxytocin group also had caesareans because of fetal distress.

2. Fletcher HM, Mitchell S et al. Intravaginal misoprostol as a cervical ripening agent, British J of Obstet Gynaec 100 (1993): 641-4.

This Jamaican study illustrates how little thought was given to dosage in the earlier trials of misoprostol for induction of labor. Participants in this double-blind clinical trial were given 100 microgram doses of misoprostol inserted vaginally (twice the amount given in the Jamaican study). The misoprostol group was compared with a group of women given a placebo that looked similar to the misoprostol white powder which was used.

Incidentally, this study is one of the few I found which involved the use of a placebo; most comparison groups in studies which followed this one were given some other induction drug.

24 women were given misoprostol.
21 were given the placebo.

If the women in either group hadn’t started labor within 12 hours, they were sent to the labour ward for oxytocin induction.

Results: the women in the misoprostol group began labor sooner than in the placebo group (15.6 hours, compared with 43.2 hours).

Fewer women in the misoprostol group required oxytocin under the standard mentioned above.

One woman in the misoprostol group had tachysystole (hyperstimulation of the uterus).

Two babies in the misoprostol group had meconium staining, compared with no babies in the placebo group.

Caesarean and forceps rates were similar in both groups.

The authors stress that uterine activity should be closely monitored following use of misoprostol.

3. Fletcher H, Mitchell S et al. Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents, Obstet Gynecol 83 (1994): 244-7.

Here we have the same Jamaican authors studying 45 women, 32 of whom were given misoprostol, with an additional 31 women being given dinoprostone to ripen the cervix and induce labor. Again, the dose was 100 micrograms of misoprostol, inserted vaginally. According to the authors, “There were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications” between the two groups