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.     

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.     

Sublingual vs. vaginal misoprostol for induction of labor.

OBJECTIVE: To compare sublingual with vaginal misoprostol for the induction of labor. METHODS: This double-blind clinical trial randomized 150 women to receive every 6 h 25 mug of sublingual misoprostol and vaginal placebo or 25 mug of vaginal misoprostol and sublingual placebo. Maternal and neonatal outcomes were analyzed and risk ratios (RRs) with 95% confidence intervals (CIs) calculated. The significance level was 5%. RESULTS: Vaginal delivery rates were 57% in the sublingual group and 69% in the vaginal group (RR, 0.8; 95% CI, 0.6-1.1). There were 11 cases of fetal distress in the sublingual group and 4 cases in the vaginal group (RR, 2.7; 95% CI, 0.9-8.2). There were no significant differences in the number of doses needed, interval between first dose and delivery, incidence of contractility disturbances, or neonatal results. CONCLUSION: The administration of misoprostol 25 mug by the sublingual route was neither more effective nor safer than the same dose administered vaginally.     

Ensayo clínico aleatorizado para evaluar la eficacia y seguridad de la administración de 25 μg de misoprostol por vía vaginal frente a 50 μg por vía sublingual para la inducción del trabajo del parto en gestantes con diabetes

Objective

To evaluate the safety and efficacy of misoprostol 50 μg administered sublingually versus 25 μg administered vaginally for labor induction at term in pregnant women with diabetes.

Methods

Three hundred pregnant women with diabetes were randomly allocated to receive misoprostol 25 μg vaginally or 50 μg sublingually every 4 hours up to 4 doses. The main variable assessed was the rate of vaginal deliveries in 24 hours.

Results

Vaginal delivery in 24 hours was achieved in 109/150 (72.7%) women in the sublingual group and in 104/150 (69.3%) in the vaginal group, with no statistically significant differences (p = 0.611; RR = 1.176; 95% CI for RR, 0.714-1.938). Tachysystole was significantly more frequent in the sublingual misoprostol group (RR = 0.474; 95% CI for RR, 0.233-0.968). The indications for cesarean section were similar in both groups. Uterine rupture occurred in one patient in the sublingual group who was administered the third misoprostol dose in the active phase of labor.

Conclusions

No statistically significant differences were found in the vaginal delivery rates between sublingual and vaginal misoprostol, although adverse effects were more frequent with the sublingual route.     

Misoprostol 50 microg sublingually versus vaginally for labor induction at term: a randomized study

OBJECTIVE: To compare the efficacy of misoprostol 50 mug vaginally and 50 mug sublingually for labor induction at term. MATERIALS AND METHODS: One hundred and sixty women were randomized to receive misoprostol 50 microg vaginally (n = 80) or 50 microg sublingually misoprostol (n = 80). The doses were given every 4 h (maximum 6 doses). Primary outcome measure was number of cesarean deliveries. Induction to delivery time, delivery within 24 h, the number of misoprostol doses given; the need for oxytocin augmentation, tachysystole and uterine hyperstimulation rates and neonatal outcomes were secondary outcome measures. RESULTS: The mean induction to delivery time was 748 +/- 379 min in the vaginal group and 711 +/- 425 in the sublingual group (p = 0.56). The number of women delivering within 24 h was 73 (91.3%) in the vaginal group and 74 (92.5%) in the sublingual group (p = 0.78). The mean number of misoprostol doses required was significantly higher in the sublingual group (1.9 +/- 1.2) compared with the vaginal group (1.1 +/- 0.4; p < 0.001). More women in the sublingual group experienced tachysystole (n = 14, 17.5%) compared with the vaginal group (n = 3, 3.8%; p = 0.005). Seven cases (8.8%) in the vaginal group and 12 cases in the sublingual group (15%) required emergent cesarean delivery for fetal heart rate abnormalities (p = 0.22). Other neonatal outcomes including umbilical artery pH, Apgar scores and intensive care unit admission were similar in the two groups. CONCLUSION: Sublingual misoprostol is as efficacious as vaginal misoprostol for induction of labor. More frequent tachysystole is observed with misoprostol 50 microg sublingually, but neonatal outcomes are similar.     

Oral misoprostol (100 microg) versus vaginal misoprostol (25 microg) in term labor induction: a randomized comparison

OBJECTIVE: To compare the efficacy of vaginal misoprostol (25 microg) to oral misoprostol (100 microg) in labor induction at term. METHODS: One hundred and one women at term, with indications for labor induction and cervical Bishop's scores of less than 8, were randomly assigned to receive 100 microg of oral misoprostol or 25 microg vaginal misoprostol after random allocation. This could be repeated every 4 h to a maximum of five doses. The number delivering vaginally within 24 h of the induction was the main outcome measure. RESULTS: Of those who delivered vaginally (74.5% in the oral group vs. 72% in the vaginal group), significantly fewer women delivered within 24 h of induction in the oral group (42.1% vs. 72.2%, RR 0.6, 95% CI 0.4-0.9), with more women receiving more than one dose (45.7% vs. 16.7%, RR 2.7, 95% CI 1.2-6.0). More women in the oral group received oxytocin (68.6% vs. 44%, RR 1.6, 95% CI 1.1-2.2), and the induction to delivery interval was shorter in the vaginal group, although this was not statistically significant [28.9 h (SD 20.2) vs. 20.6 h (SD 16.1), mean difference - 8.3 h, 95% CI - 16.8 to 0.2]. There were no differences in the modes of delivery, uterine hyperstimulation rates or in the neonatal outcomes. CONCLUSION: Vaginal misoprostol in its currently recommended dose of 25 microg seems to be more efficacious than the 100 microg oral dose.     

Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel.

OBJECTIVE: To compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term. DESIGN: A single-blind randomised comparative trial. SETTING: Induction and labour wards of a UK teaching hospital. PARTICIPANTS: Two hundred and eleven pregnant women at term in whom induction of labour was indicated, and with no contra-indication to the use of prostaglandins for the induction of labour. INTERVENTION: The women were randomly assigned to receive vaginal administration of either misoprostol 50 microg four hourly (to a maximum of four doses) or dinoprostone gel 1 mg six hourly (to a maximum of three doses). MAIN OUTCOME MEASURES: Time from induction to delivery, oxytocin requirement in labour, analgesic requirement, mode of delivery, neonatal outcome. RESULTS: The misoprostol group had a highly significant reduction in median induction-delivery interval compared with the dinoprostone group (14.4 hours vs 22.9 hours; P < 0.00001). In addition, more women delivered after only one dose (77% vs 49%; P < 0.0001, OR 3.51, 95% CI 1.94-6.35), and within 12 and 24 hours. There was a reduced need for oxytocin augmentation in labour (21% vs 47%; P < 0.0001, OR 0.30, 95% CI 0.16-0.54). There was no difference in analgesia requirement in labour, or in mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. Women in the misoprostol group experienced more pain in the interval between induction and being given analgesia in labour, but this did not reach statistical significance. CONCLUSIONS: Misoprostol 50 microg vaginally is a more effective induction agent than 1 mg dinoprostone vaginal gel, with no apparent adverse effects on mode of delivery, or on the fetus. The higher pain scores in the misoprostol group must be balanced against the reduction in time spent having labour induced, and the reduction in need for intravenous oxytocin augmentation. Further randomised studies must continue to exclude the possibility of rare adverse side effects.     

Misoprostol compared with prostaglandin E2 for labour induction in women at term with intact membranes and unfavourable cervix: a systematic review

BACKGROUND: Misoprostol is a commonly used prostaglandin to induce labour. A potential risk of induction, however, is caesarean delivery, especially in women with an unfavourable cervix. OBJECTIVES: To evaluate the use of misoprostol, compared with prostaglandin E2 (PgE2), for labour induction in women at term with an unfavourable cervix and intact membranes. SEARCH STRATEGY: PubMed, Medline, EMBASE and the Cochrane Library were searched for articles published in any language from January 1987 to December 2005, using the keywords 'misoprostol', 'labour/labor' and 'induction'. SELECTION CRITERIA: We identified randomised trials of women at term (> or =37 weeks of gestation) with intact membranes and unfavourable cervix, undergoing labour induction with misoprostol, orally, vaginally, sublingually or buccally, compared with PgE2 vaginally or intracervically. DATA COLLECTION AND ANALYSIS: Caesarean delivery was the primary outcome, with tachysystole and hyperstimulation as secondary outcomes. The primary analysis compared any misoprostol with any PgE2 for all women, with a subgroup analysis for nulliparous women. Secondary analyses compared different routes and doses of misoprostol (oral or vaginal and 25 microgram or >25 microgram) and PgE2 (intracervical or vaginal). Relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models.Main results Fourteen of 611 articles identified met the criteria for systematic review, with three providing information for nulliparous women. There was no difference in the risk of caesarean delivery between misoprostol and PgE2 groups (RR = 0.99, 95% CI = 0.83-1.17). Any misoprostol was associated with higher risks of tachysystole and hyperstimulation compared with any PgE2 (RR = 1.86, 95% CI = 1.01-3.43 and RR = 3.71, 95% CI = 2.00-6.88, respectively). There was a higher rate of vaginal delivery within 24 hours among all vaginal deliveries with any misoprostol compared with any PgE2 (RR = 1.14, 95% CI = 1.00-1.31), and among all deliveries, a lower rate of oxytocin use (RR = 0.71, 95% CI = 0.60-0.85) but a trend towards increased meconium staining was observed (RR = 1.22, 95% CI = 0.96-1.55). The use of misoprostol at starting dosages >25 microgram had similar findings to the primary analysis. Studies of lower misoprostol dosing (starting dose of 25 microgram) did not show any differences in the outcomes of interest, but the sample size of this secondary analysis was small (304 women, 155 receiving misoprostol). AUTHOR'S CONCLUSIONS: Although misoprostol in women at term with an unfavourable cervix and intact membranes was more effective than PgE2 in achieving vaginal delivery within 24 hours, misoprostol does not reduce the rate of caesarean delivery either in all women or in the subgroup of nulliparous women, and it increases the rates of tachysystole and hyperstimulation. Further studies of misoprostol using a starting dose of 25 microgram may be warranted.     

A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor

OBJECTIVE: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor. STUDY DESIGN: Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis. RESULTS: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05). CONCLUSION: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.     

Oral versus vaginal misoprostol for induction of labor: a double-blind randomized controlled trial

OBJECTIVE: To determine the efficacy of oral misoprostol (50 microg) administered every 3 hours compared to vaginal misoprostol (50 microg) administered every 6 hours for induction of labor. STUDY DESIGN: In this double-blind randomized trial, 126 women received misoprostol (50 microg) either orally every 3 hours or vaginally every 6 hours for induction of labor. Outcomes included time from induction to delivery, oxytocin augmentation, incidence of hyperstimulation and tachysystole, mode of delivery, and neonatal outcomes. RESULTS: Median time to delivery was shorter in those women who were receiving vaginal misoprostol (vaginal 14.3 hours vs oral 23.1 hours; P =.0004) and more women in the oral group required oxytocin augmentation of labor (73% vs 42%) (RR, 1.98; 95% CI, 1.29 to 3.06). The incidence of hyperstimulation was similar between the groups, but there was an increased incidence of tachysystole in the vaginal group (26.5% vs 9.7%)(RR, 2.74; 95% CI, 1.16 to 6.51). There was no difference between the groups with respect to mode of delivery or neonatal outcome. CONCLUSION: Vaginal misoprostol administered every 6 hours is more effective for induction of labor than oral misoprostol administered every 3 hours. The higher rates of tachysystole with use of vaginal misoprostol in the current study warrant further investigation.     

Comparative Evaluation of 50 Microgram Oral Misoprostol and 25 Microgram Intravaginal Misoprostol for Induction of Labour at Term: A Randomized Trial

ObjectivesTo assess and compare the efficacy and safety of 50 μg oral misoprostol and 25 μg intravaginal misoprostol for induction of labour at term.MethodsThis non-blinded, randomized clinical trial included 228 pregnant women at term with obstetric or medical indications for induction of labour. Women either took 50 μg misoprostol orally (two 25 μg tablets) or had one 25 μg tablet of misoprostol inserted in the posterior vaginal fornix. In each group, misoprostol administration was repeated every four hours in the same dose until regular uterine contractions were established or to a maximum of five doses. Time to delivery and outcome data for each group were compared.ResultsOf the 228 women, eight (3.5%) were excluded from the analysis as they withdrew their consent after randomization. Mean induction-to-delivery interval was similar in both groups (21.22 hours in the oral group vs. 20.15 hours in the vaginal group; P = 0.58). There was no significant difference between the groups with respect to the number of women who delivered within 24 hours or who required oxytocin augmentation of labour, the mode of delivery, and neonatal outcomes (P > 0.05). Uterine hyperstimulation occurred in two women who received misoprostol vaginally, but not in any of the women in the oral misoprostol group.ConclusionOral misoprostol in a dose of 50 μg every four hours, to a maximum of five doses, has the potential to induce labour as safely and effectively as 25 μg misoprostol administered vaginally every four hours.     

Randomized comparison of 3 misoprostol protocols for abortion induction at 13-20 weeks of gestation

OBJECTIVE: To evaluate the induction-to-abortion time of 3 pharmacokinetic-based protocols at 13-20 weeks of gestation. STUDY DESIGN: A randomized trial was conducted on 153 patients. The oral group (n = 51) received 100 microg misoprostol orally every 2 hours, the vaginal group (n = 51) received 200 microg misoprostol vaginally every 4 hours, and the sublingual group (n = 51) received 100 microg misoprostol sublingually every 2 hours. RESULTS: The mean induction-to-delivery time was shorter in the sublingual group (mean, 651 +/- 507) as compared to the vaginal group (mean, 1,056 +/- 634, p = 0.01). The number of patients who delivered within 12 hours was significantly higher in the sublingual group (n = 39, 78%) as compared to the oral (n = 26, 52%) and vaginal (n = 20, 40%) groups (p < 0.001). The numbers of patients who delivered within 24 hours were comparable in the sublingual (n = 47, 94%) and oral (n = 46, 92%) groups but higher than in the vaginal group (n = 39, 78%; p = 0.02). The total misoprostol dose was 543 +/- 422 microg in the sublingual group, 878 +/- 533 microg in the vaginal group and 741 +/- 413 microg in the oral group (p < 0.001). CONCLUSION: A pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4 hours is more effective for induction of second-trimester abortion as compared to 100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol every 4 hours.     

Labor induction at term: a comparison of the effects of 50 microg and 25 microg vaginal misoprostol

PURPOSE OF INVESTIGATION: To compare the effects of 50 microg of vaginal misoprostol with 25 microg for labor induction at term. METHODS: One hundred and forty-seven pregnant women with indications for labor induction and cervical Bishop's score of < or = 6 were randomly assigned to receive either 50 microg (n = 74) or 25 microg (n = 73) of vaginal misoprostol every four hours until either a Bishop's score of > or = 8 or adequate uterine contraction frequency had been achieved. Induction-to-vaginal-delivery time was considered the primary outcome measure. RESULTS: Mean induction-to-vaginal-delivery time was significantly shorter in the 50-microg group than in the 25-microg group (526 +/- 141 min vs 745 +/- 218 min, respectively); oxytocin was administered to 65.8% of the patients in the 25-microg group and to 35.1% in the 50-microg group (p < .05). The incidence of tachysystole was significantly higher in the 50-microg group than in the 25-microg group (12% vs 2.7%, p < .05). We found no statistically significant difference between the two groups with respect to the rate of primary cesarean section, incidence of hyperstimulation syndrome, or neonatal outcome (p > .05). CONCLUSION: Fifty micrograms of vaginally administered misoprostol is an effective and inexpensive means of inducing labor at term. Uterine tachysystole may be associated more frequently with a 50-microg dose of vaginal misoprostol than with a 25-microg dose. Clinicians must accurately document the frequency and intensity of uterine contractions before every 50-microg dose of misoprostol is administered.     

Titrated oral misoprostol solution for induction of labour: a multi-centre, randomised trial

Objectives To determine the effects of titrated oral misoprostol solution, compared with vaginal dinoprostone.
Study design Open, randomised clinical trial.
Setting Academic hospitals in South Africa and Liverpool, UK.
Methods Women undergoing induction of labour after 34 weeks of pregnancy were allocated by randomised, sealed opaque envelopes, to induction of labour with titrated oral misoprostol solution, or two doses of vaginal dinoprostone (2mg) administered six hours apart. Failure to deliver within 24 hours of randomisation was the primary outcome on which the sample size was based. The data were analysed by intention-to-treat.
Results Six hundred and ninety-five women were randomly allocated: 346 to oral misoprostol and 349 to vaginal dinoprostone. There were no significant differences in substantive outcomes. Vaginal delivery within 24 hours was not achieved in 38% of women in the oral misoprostol group and 36% in the vaginal dinoprostone group (RR 1.08; 95% CI 0.89-1.31). The caesarean section rates were 16% and 20%, respectively (RR 0.80; 95% CI 0.58-1.11). Hyperstimulation with fetal heart rate changes occurred in 4% of women in the oral misoprostol group and 3% after vaginal dinoprostone (RR 1.32, 95% CI 0.59–2.98). The response to induction of labour in women with unfavourable cervices was somewhat slower with misoprostol when membranes were intact, and with dinoprostone when membranes were ruptured. There were no differences in neonatal outcome between the two groups.
Conclusions This new approach to oral misoprostol administration was successful in minimising the risk of uterine hyperstimulation, which has been a feature of misoprostol use for induction of labour, at the expense of a somewhat slower response in women with intact membranes and unfavourable cervices. Misoprostol is not registered for use in pregnant women, and further research is needed to confirm optimal and safe dosages.     

A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation

OBJECTIVE: To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. DESIGN: Randomised controlled trial. SETTING: Aberdeen Royal Infirmary. POPULATION: Women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Women's acceptability, efficacy of the regimen and side effects experienced. RESULTS: A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). CONCLUSIONS: Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.     

Controlled-release misoprostol vaginal insert in parous women for labor induction: a randomized controlled trial

OBJECTIVE: To assess the ability of a controlled-release misoprostol vaginal insert to induce labor using dose reservoirs of 25, 50, 100, and 200 microg. METHODS: This double-blind, dose ranging, randomized study was carried out in parous women requiring induction of labor at term. Each woman was randomly assigned to receive a single misoprostol vaginal insert that could remain in place for up to 24 hours and was removed for onset of active labor, an adverse event, or having reached 24 hours in situ. The primary outcome measure was time from insertion of the misoprostol vaginal insert to vaginal delivery of the neonate. RESULTS: A total of 124 women participated in the study. The median time to vaginal delivery was 27.5, 19.1, 13.1, and 10.6 hours for the 25-, 50-, 100-, and 200-microg doses, respectively. The percentage of women who delivered vaginally within 12 hours was 9%, 14%, 47%, and 53% (P<.001 using the 25-microg group as the comparator) and within 24 hours was 42%, 79%, 81%, and 70% (P=.003). Uterine hyperstimulation syndrome occurred in one woman who received the 25-mug, two women who received the 100-microg, and three women who received the 200-microg dose reservoirs. CONCLUSION: Misoprostol vaginal inserts effectively induced labor in pregnant parous women at term. LEVEL OF EVIDENCE: I.     

A randomised double blind trial comparing misoprostol or placebo in the management of early miscarriage

OBJECTIVES: To study if misoprostol 400 microg, administered vaginally, increased the successful resolution of early miscarriage compared with placebo. DESIGN: Randomised, double blind placebo controlled study. SETTING: Sahlgrenska University Hospital, G?teborg, Sweden. SAMPLE: One hundred and twenty-six women seeking medical attention for early miscarriage. METHOD: Women with a non-viable, first trimester miscarriage were randomised to vaginal administration of misoprostol 400 microg or placebo. MAIN OUTCOME MEASURES: Main outcome measure was the proportion of successful complete resolution of miscarriage. Secondary outcomes were incidence of infection, bleeding, gastrointestinal side effects, pain, use of analgesics and length of sick leave between groups. RESULTS: Sixty-four patients were randomised to misoprostol and 62 to placebo. Eighty-one percent in the misoprostol and 52% in the placebo group had a complete miscarriage within one week of the primary visit (RR 1.57; 95% CI 1.20-2.06). Patients in the misoprostol group reported more pain as assessed on a visual analogue scale (60.4 [31.0] vs 43.8 [37.1] mm; P < 0.007) and required analgesics more often (83%vs 61%, RR 1.35; 95% CI 1.08-1.70). There were no significant differences in the occurrence of gastrointestinal side effects, infection, reduction in haemoglobin or sick leave between the groups. CONCLUSIONS: Treatment with 400 mug misoprostol administered vaginally increased the success rate of resolvement of uncomplicated early miscarriages compared with placebo. However, women who received misoprostol experienced more pain and required more analgesics than those who did not.     

A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy

OBJECTIVE: To compare the efficacy, side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary referral unit and a teaching hospital. POPULATION: Two hundred and twenty-four women at 12 to 20 weeks of gestation. METHODS: The women were randomised to receive either sublingual or vaginal misoprostol 400 microg every 3 hours for a maximum of five doses. The course of misoprostol was repeated if the woman did not abort within 24 hours. MAIN OUTCOME MEASURES: The success rate at 48 hours, induction-to-abortion interval and the side effects. RESULTS: There was no significant difference in the success rate at 48 hours (sublingual: 91%; vaginal: 95%). However, the success rate at 24 hours was significantly higher in the vaginal group (85%) compared with the sublingual group (64%). There was no difference in the median induction-to-abortion interval (sublingual: 13.8 hours; vaginal: 12.0 hours). Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group. The incidence of fever was also less in the sublingual group. CONCLUSION: The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours. Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative.     

A randomised controlled trial comparing low dose vaginal misoprostol and dinoprostone vaginal gel for inducing labour at term

OBJECTIVE: To compare the efficacy of low dose vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term. DESIGN: A single-blind randomised controlled trial. SETTING: Antenatal and labour ward of a UK district general hospital. PARTICIPANTS: Two hundred and sixty-eight women requiring induction of labour at term (>37 weeks of gestation) with no significant fetal or medical condition, no previous uterine surgery and no contraindication to prostaglandin. METHODS: Misoprostol 25 microg (one-quarter of a 100 microg tablet) was inserted into the posterior vaginal fornix every 4 hours (to a maximum of six doses) or dinoprostone vaginal gel 1-2 mg 6 hourly (maximum of 3 mg in 24 hours). MAIN OUTCOME MEASURE: Induction-to-vaginal delivery interval. SECONDARY OUTCOME MEASURES: Requirements for oxytocin, mode of delivery, number of women delivering < 24 hours, incidence of uterine contraction abnormalities, incidence of abnormal cardiotocograph (CTG) recordings, 5-minute Apgar scores, umbilical cord pH recordings, analgesia requirements, admission to NICU and blood loss at delivery. RESULTS: There were no significant differences between the two groups in induction-to-vaginal delivery interval, mode of delivery, number of women delivering within 24 hours and neonatal outcomes. The incidence of uterine contraction abnormalities (tachysystole and hyperstimulation) and the incidence of abnormal CTG recordings were also similar for both groups. CONCLUSION: Low dose vaginal misoprostol is as effective as dinoprostone gel for inducing labour at term. There would be substantial cost savings, estimated at around 3.9 million UK pounds per annum, for maternity services if low dose misoprostol became the agent of choice for inducing labour in the UK.     

Induction of labour in nulliparous and multiparous women: a UK, multicentre, open-label study of intravaginal misoprostol in comparison with dinoprostone

Objective  To compare the efficacy and safety of a 25-microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3-mg vaginal tablet) in cervical ripening and labour induction.
Design  A randomised, open-label, noninferiority, comparative study in two maternal populations.
Setting  Eighteen NHS study centres across the UK.
Population  Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour.
Methods  Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score ≤4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome.
Main outcome measures  The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes.
Results  A total of 626 women were randomised to misoprostol ( n = 318) or dinoprostone ( n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI −3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups.
Conclusions  Low-dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.