Titrated oral misoprostol solution versus vaginal misoprostol for labor induction

Objective

To determine the efficacy and safety of a titrated oral misoprostol solution compared with vaginal misoprostol tablets for labor induction.

Methods

A randomized, triple-blind, multicenter clinical trial was conducted between March 2010 and June 2011. Women with a single gestation (n = 200) were randomized to receive a titrated oral misoprostol solution (initial misoprostol dose 20 μg/hour; dose increased by 20 μg/hour every 6 hours up to 80 μg/hour for a maximum of 48 doses) or vaginal misoprostol tablets (25 μg of misoprostol every 6 hours for a maximum of 8 doses). Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for maternal and perinatal outcomes.

Results

The frequencies of vaginal delivery not achieved within 12 hours (RR 0.87; 95% CI, 0.62–1.22) and within 24 hours (RR 1.11; 95% CI, 0.83–1.49) were similar in the 2 groups. No differences were found in terms of uterine hyperstimulation, unfavorable cervix at 12 and 24 hours, oxytocin augmentation, tachysystole, epidural analgesia, adverse effects, and perinatal outcome. Approximately 70% of the women preferred the oral solution.

Conclusion

A titrated oral misoprostol solution was as effective and safe for labor induction as vaginal misoprostol tablets.ClinicalTrial.gov: NCT00 992524     

Sublingual compared with oral misoprostol in term labour induction: a randomised controlled trial

Objective To compare the efficacy and patient acceptability of 50 μg of sublingual misoprostol with 100 μg of oral misoprostol in the induction of labour at term.
Design Non-blinded randomised comparative trial.
Setting Tertiary level UK Hospital.
Sample Two hundred and fifty women at term with indications for labour induction.
Methods Fifty micrograms of sublingual misoprostol or 100 μg of oral misoprostol was administered every four hours after random allocation, to a maximum of five doses.
Main outcome measures Number of patients delivering vaginally within 24 hours of the induction, mode of delivery, neonatal outcomes and patient acceptability.
Results There was no significant difference in the number of women delivering vaginally within 24 hours of the induction in the sublingual group as compared with the oral group (62.8% vs 59%, RR 1.1, 95% CI 0.6–2.1), or in the mean induction to delivery time (21.8 vs 24.1 h, mean difference 2.3 h 95% CI −2.2 to +6.7). There was no difference in the uterine hyperstimulation rates (1.6% in both groups), operative delivery rates or neonatal outcomes. In the sublingual group, 92.6% found the induction acceptable with 15.8% finding the tablets with an unpleasant taste, while in the oral group it was 96.9% and 4%, respectively. More patients in the oral group thought that they would consider the same method of induction again as compared with the sublingual group (58.6% vs 40%, RR 1.4, 95% CI 1.04–1.9).
Conclusion Fifty micrograms of sublingual misoprostol every four hours has the same efficacy and safety profile as compared with 100 μg orally, but the oral route might be preferred by women.     

Titrated oral compared with vaginal misoprostol for labor induction: a randomized controlled trial

OBJECTIVE: To compare the efficacy and safety of titrated oral misoprostol and vaginal misoprostol for labor induction. METHODS: Women between 34 and 42 weeks of gestation with an unfavorable cervix (Bishop score less than or equal to 6) and an indication for labor induction were randomLy assigned to receive titrated oral or vaginal misoprostol. The titrated oral misoprostol group received a basal unit of 20 mL misoprostol solution (1 mcg/mL) every 1 hour for four doses and then were titrated against individual uterine response. The vaginal group received 25 mcg every 4 hours until attaining a more favorable cervix. Vaginal delivery within 12 hours was the primary outcome. The data were analyzed by intention-to-treat. RESULTS: Titrated oral misoprostol was given to 101 (48.8%) women and vaginal misoprostol to 106 (51.2%) women. Completed vaginal delivery occurred within 12 hours in 75 (74.3%) women in the titrated oral group and 27 (25.5%) women in the vaginal group (relative risk [RR] 8.44, 95% confidence interval [CI] 4.52-15.76). The incidence of hyperstimulation was 0.0% in the titrated oral group compared with 11.3% in the vaginal group (RR 0.08, 95% CI 0.01-0.61). Although more women experienced nausea (10.9%) in the titrated oral group (RR 27.07, 95% CI 1.57-465.70), fewer infants had Apgar scores of less than 7 at 1 minute in the titrated oral group than in the vaginal group (RR 0.10, 95% CI 0.01-0.76). CONCLUSION: Titrated oral misoprostol is associated with a lower incidence of uterine hyperstimulation and a lower cesarean delivery rate than vaginal misoprostol for labor induction in patients with unfavorable cervix. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00529295 LEVEL OF EVIDENCE: I.     

Sublingual compared with vaginal misoprostol for labour induction at term: a randomised controlled trial

OBJECTIVE: To compare the efficacy and safety of 50 microg of sublingual misoprostol with 25 microg of vaginal misoprostol administered for labour induction at term.Design Double-blinded, randomised controlled trial.Setting University Hospital, Kaunas, Lithuania.Sample A total of 140 women at term with indications for labour induction.Methods Women were randomised to receive either 50 microg of sublingual misoprostol with vaginal placebo (n = 70) or sublingual placebo with 25 microg of vaginal misoprostol (n = 70) every 4 hours (maximum six doses).Main outcome measures The number of women delivering vaginally within 24 hours of labour induction.Results Fifty-eight women (83%) in the sublingual misoprostol group and 53 (76%) in the vaginal misoprostol group delivered vaginally within 24 hours [relative risk (RR) 1.1, 95% confidential interval (CI) 0.9-1.3]. However, the induction to vaginal delivery time was significantly shorter in the sublingual group (15.0 +/- 3.7 hours) compared with the vaginal group (16.7 +/- 4.1 hours, P = 0.03). The incidence of tachysystole was more than three-fold higher in the sublingual than in the vaginal group (14 versus 4.3%; RR 3.3, 95% CI 0.9-11.6), but this was not statistically significant. There were no significant differences in the incidence of hypertonus or hyperstimulation syndrome, mode of delivery, interventions for fetal distress or neonatal outcomes between the two groups.Conclusion A 50 microg of sublingual misoprostol 4 hourly for labour induction at term seems to have similar efficacy as 25 microg of vaginal misoprostol. Further studies on safety with larger numbers of women need to be conducted before routine sublingual misoprostol use in this setting.     

A randomised trial comparing low dose vaginal misoprostol and dinoprostone for labour induction

Objective   To compare vaginal misoprostol with dinoprostone for induction of labour.
Design   Randomised multicentre trial.
Setting   Labour wards of one university hospital and two teaching hospitals.
Population   Six hundred and eighty-one women with indication for labour induction at ≥36 weeks of gestation, singleton pregnancy and no previous ceasarean section.
Methods   Misoprostol (25 mcg, hospital-prepared capsule) in the posterior vaginal fornix, every four hours, maximum three times daily or dinoprostone gel (1 mg) every four hours. Oxytocin was administered if necessary.
Main outcome measures   Primary: 'adverse neonatal outcome' (5-minute Apgar score <7 and/or umbilical cord pH <7.15). Secondary: labour duration, mode of delivery and patient satisfaction.
Results   Three hundred and forty-one women received misoprostol and 340 dinoprostone. The median induction–delivery interval was longer in the misoprostol group compared with the dinoprostone group (25 versus 19 hours, P = 0.008). The caesarean section rate was lower in the misoprostol group: 16.1% versus 21%, but this difference was not statistically significant RR = 0.8 (95% CI 0.6–1.04). 'Adverse neonatal outcome' was found to be similar in both groups: 21% in the misoprostol and 23% in the dinoprostone groups. Significantly fewer neonates were admitted to NICU in the misoprostol group compared with dinoprostone 19% versus 26% (RR = 0.7, 95% CI 0.5–0.98).
Conclusions   Misoprostol in this dosing regimen is a safe method of labour induction. NICU admission rates were lower in the misoprostol group. No difference could be detected in patient satisfaction between groups.     

A randomised placebo controlled trial of oral misoprostol in the third stage of labour

Objective To compare oral misoprostol 400 μg with placebo in the routine management of the third stage of labour.
Design A double-blind placebo controlled trial.
Setting The labour ward of an academic hospital in Johannesburg, South Africa with 7000 deliveries per annum.
Participants Low-risk women expected to deliver vaginally.
Methods Women in labour were randomly allocated to receive either misoprosto1 400 μg orally or placebo after the birth. Conventional oxytocics were given immediately if blood loss was thought to be more than usual. Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan. Side effects were recorded.
Main outcome measures Measured blood loss ≥ 2 1000 ml within the first hour after birth. Use of additional oxytocics.
Results The groups were well matched. Measured blood loss ≥ 1000 ml occurred in 15/250 (6%) after misoprostol and 23/250 (9%) after placebo (relative risk 0.65; 95% confidence interval 0.35–1.22). The difference may have been reduced by the greater use of conventional oxytocics in the placebo group, which was statistically significant for intravenous oxytocin infusion (2.8% vs 8.4%, relative risk 0.33, 95% confidence interval 0.140.77). Shivering was more common in the misoprostol group (190/, vs 5%, relative risk 3.69; 95% confidence interval 2.05-6.64).
Conclusions Shivering has been shown in this study to be a specific side effect of misoprostol administered orally in the puerperium. No serious side effects were noted. Misoprostol shows promise as a method of preventing postpartum haemorrhage. Because of the potential benefits for childbearing women, particularly those in developing countries, further research to determine its effects with greater certainty should be expedited.     

Combination of misoprostol and mechanical dilation for induction of labour: a randomized controlled trial

Objective

To evaluate a combination of oral misoprostol (OM) and mechanical dilation of the cervix to improve efficacy in inducing labour.

Study design

This prospective, randomized study included 122 term pregnancies with an indication for induced labour. Each woman was randomly assigned to one of two groups. In the study group, a combination of OM and mechanical dilation with a double-balloon catheter for cervical ripening was used. In the control group, only OM was administered. The primary outcome measure was the rate of failure to induce labour, defined as no vaginal delivery within 48 h.

Results

In the study group, the rate of failure to induce labour was significantly lower in comparison with the control group (9.3% vs. 21.2%; P = 0.007). The median times for inducing labour were 15.3 h in the study group and 20.8 h in the control group (P = 0.158). There were no significant differences between the two groups with regard to other outcome parameters. As there were no failures of induced labour among women with premature rupture of membranes, the study results were also evaluated after excluding these cases. Among those women without rupture of membranes, the median times for induction were 15.8 h in the study group and 32.6 h in the control group (P = 0.024). The rates of failure to induce labour were 10.8% vs. 28.2% (P = 0.002).

Conclusion

A combination of OM and a double-balloon catheter improves the efficacy of labour induction in term pregnancies, particularly in women without premature rupture of the membranes.     

口服米索前列醇引产

1背景 本评价是用标准计划书系列引产方法的系统评价之一。方法学原理的更详细资料，请参阅最近出版的一般项目计划书（Hofmeyr 2000）。一般项目计划书描述了如何将多个标准化的评价合并起来，以比较促宫颈成熟和引产的不同方法。     

A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term

OBJECTIVE: To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level, teaching Scottish Hospital. POPULATION: Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. METHODS: The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). MAIN OUTCOME MEASURE: The number delivering vaginally within 24 hours of the induction. RESULTS: Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group. CONCLUSIONS: Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.     

Dysfunctional labour: a randomised trial

Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (   P = 0.144  and 0–0.06, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.     

Ruptured membranes at term: randomized,double-blind trial of oral misoprostol for labor induction

OBJECTIVE: To determine if oral misoprostol can replace oxytocin for labor stimulation in women with ruptured membranes at term and without evidence of labor. METHODS: Nulliparous women at 36 to 41 weeks with a singleton, cephalic-presenting fetus and ruptured membranes without evidence of labor were randomized to receive oral misoprostol (100 microg) or a placebo every 4 hours for a maximum of two doses. Intravenous oxytocin was initiated if active labor had not ensued within 8 hours of the initial study drug dose. RESULTS: Fifty-one women were randomized to oral misoprostol and 51 women to the placebo. Misoprostol reduced the use of oxytocin stimulation of labor from 90% to 37% (P <.001) and was associated with approximately a 7-hour shorter elapsed time in the labor unit. Uterine hyperactivity, defined as six or more contractions in 10 minutes without fetal heart rate decelerations, occurred in 25% of women randomized to misoprostol. However, uterine hyperactivity associated with fetal heart rate decelerations occurred in only three (6%) women, none of whom required emergency cesarean delivery. Route of delivery and infant outcomes were not related to misoprostol use. CONCLUSION: Oral misoprostol (100 microg) given in a maximum of two doses 4 hours apart significantly reduced the use of oxytocin in the management of women with ruptured membranes without labor at term.     

Induction of labour with a viable infant: a randomised clinical trial comparing intravaginal misoprostol and intravaginal dinoprostone

Objective To compare the efficacy and safety of vaginal misoprostol (50μg) with vaginal dinoprostone.
Design Double-blind randomised trial.
Setting Obstetrics Department, Poissy Hospital, France.
Participants 370 patients with medical indications for induction of labour.
Outcome measures Vaginal deliveries within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs, and fetal, neonatal and maternal condition.
Results Compared with vaginal dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas: vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery within 12 hours. There was a non-significant increase in the caesarean section rate for fetal distress in the misoprostol group, but fewer caesarean sections for failed induction. Fetal tolerance was similar in the two groups, although significantly more neonates had a cord  pH <7.20  and (non-significantly) none had meconium stained amniotic fluid in the misoprostol group. The incidence of poor neonatal outcome was similar in both groups. Subgroup analysis by indication for induction showed that the higher rates of arterial cord  pH <7.20  and of meconium-stained amniotic fluid with misoprostol persisted only in possible fetal compromise. Poor neonatal outcome was less frequent in the misoprostol group in cases of induction for non-fetal indications.
Conclusions Vaginal misoprostol resulted in successful and earlier induction of labour more often than dinoprostone, but the safety of misoprostol raises some concern in potentially compromised infants. Misoprostol should be preferred to dinoprostone in cases of induction for non-fetal indications.     

A comparison between intravaginal and oral misoprostol for labor induction: a randomized controlled trial

AIM: To compare the effectiveness and safety between intravaginal and oral misoprostol for labor induction. METHODS: One hundred and six pregnant women at term with unfavorable cervix (Bishop score < or = 4) and no contraindication to prostaglandin therapy were randomized to receive either intravaginal misoprostol 50 microg every 4 h or oral misoprostol 50 microg every 4 h for prospective randomized controlled trial study. Treatment interval from induction to vaginal delivery, maternal and neonatal complications were the main outcome measures. RESULTS: There were no statistical differences of baseline characteristics and Bishop score prior to intervention between both groups. Time interval from induction to vaginal delivery in the oral group was slightly, but significantly, longer than that of the intravaginal group (886.1 +/- 443.5 min vs 637.0 +/- 373.3 min, respectively.) Additionally, the number of doses required was significantly higher in the oral group. Nonetheless, there was no significant difference between both groups with regard to failure of induction and maternal-neonatal complications. CONCLUSION: The effectiveness in terms of failed induction and safety were comparable between intravaginal and oral misoprostol, but intravaginal route was better with respect to treatment interval and number of required doses. Both routes of administration can alternatively be used for labor induction.     

Intravaginal administration of isosorbide mononitrate and misoprostol for cervical ripening and induction of labour: a randomized controlled trial

Background  

Labor induction in the presence of unfavorable cervix is a common indication for the use of prostaglandins. However, in the last years, there has been a considerable interest in the use of nitrous oxide donors for cervical ripening and labor induction.     

Sublingual misoprostol for labor induction: a randomized clinical trial

OBJECTIVE: To compare the effectiveness of 50 microg compared with 100 microg of repetitive misoprostol dosages administered sublingually for labor induction. METHODS: Two hundred twelve women who presented with an indication for cervical ripening and labor induction were randomly assigned to 50 microg or 100 microg of misoprostol tablets administered sublingually with double masking of treatment group dose allocation. The primary outcome was the interval from start of induction to vaginal delivery. RESULTS: Among the 203 evaluable participants, 102 were randomly assigned to the 50-microg group and 101 to the 100-microg group. The proportion of patients who delivered vaginally in less than 12 hours and less than 24 hours was significantly higher in the 100-microg group: 28% and 63% in the 100-microg group compared with 15% and 36% in the 50-microg group, respectively (P = .01 and P = .001). The incidence of tachysystole was significantly higher in the 100-microg group (P = .02). The incidence of hyperstimulation syndrome was higher in the 100-microg group, but not statistically significant (P = .46). With respect to the proportion of patients delivered after a single dose, mode of delivery, and perinatal outcome, no significant differences between treatment groups were observed. Regarding the need for oxytocin augmentation, 61% required augmentation in the 100-microg group compared with 81% in the 50-microg group (P = .002). CONCLUSION: One hundred micrograms of sublingual misoprostol is more effective than 50 microg of sublingual misoprostol, but is associated with a higher incidence of tachysystole and uterine hyperstimulation syndrome. LEVEL OF EVIDENCE: I.