Pre-induction cervical ripening: comparing between two vaginal preparations of dinoprostone in women with an unfavorable cervix

Abstract

Objective: Prostaglandin E2 (PGE2-Dinoprostone) is accepted for both ripening of the cervix and induction of labor. As conflicting data exist concerning the efficiency and safety of different treatment modalities, we aimed to compare slow-release vaginal insert PGE2 with serial vaginal tablets of PGE2 for cervical ripening and induction of labor.

Methods: A retrospective cohort study comparing all pregnancies who underwent induction of labor by either a single slow-release vaginal insert of 10?mg PGE2 (study group) to a historical control group of women who were treated with serial administration of 3?mg vaginal PGE2 tablets in a 2:1 ratio, matched by parity.

Results: Overall, 639 women were enrolled (213 treated with PGE2 tablets and 426 with slow-release vaginal inserts). Vaginal insert was associated with shorter initiation-to-ripening interval (12.4?±?7.7 versus 18.6?±?15.2?h, p?<?0.001) and a higher rate of delivery within 24?h (61.5 versus 51.6%, p?=?0.018). Vaginal insert was associated with an increased rate of tachysystole (8.0 versus 3.1%, p?<?0.01); however, the rates of cesarean section or operative delivery due to non-reassuring fetal heart rate (NRFHR) were similar. On multivariable analysis, slow-release vaginal insert was independently associated with a higher rate of delivery within 24?h (OR 1.50, 95% CI 1.04–2.18).

Conclusion: Slow-release PGE2 vaginal insert achieves cervical ripening and subsequently delivery over a shorter time period than PGE2 tablets, without increasing uterine hyperstimulation rate.     

Failure of cervical ripening with prostaglandin-E2 can it be predicted?

Objective.?To identify factors predicting failure of cervical ripening with prostaglandin E₂ (PGE₂).

Study design.?A retrospective, cohort study of all women admitted for preinduction cervical ripening and failed to respond to PGE₂ in comparison with randomly selected control group of women who underwent successful preinduction cervical ripening with PGE₂ in a 3:1 ratio.

Results.?Overall 488 women were included, of them, 122 in the study group and 366 in the control group. A comparison between the two groups has revealed that maternal age above 30 years (OR?=?2.7, 95%-CI 1.3–5.6), nulliparity (OR?=?4.1, 95%-CI 1.7–10.0), prepregnancy BMI above 25?kg/m² (OR?=?3.5, 95%-CI 1.7–7.1), cervical dilatation of 1?cm (OR?=?9.1, 95%-CI 3.5–13.4), cervical effacement of 50% or less admission (OR?=?5.0, 95%-CI 2.2–8.8), and gestational age of 37 weeks or less (OR?=?2.9, 95%-CI 1.3–6.6), are independent and significant predictors of cervical ripening failure with PGE₂, and account for almost 50% of the variation in ripening outcome (R²?=?0.47). No association was found between the risk of cervical ripening failure and the indication for ripening, rupture of membranes, weight gain during pregnancy, weight before labor, diabetes or preeclampsia during pregnancy, and the newborn weight.

Conclusions.?Characterization of women who have a high probability for cervical ripening failure with PGE₂ will help to improve consultation and may help choosing the optimal method for labor induction in these cases.     

Vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert: a retrospective study of 1656 women in China

Objective: This study aimed to qualify relevant factors for vaginal delivery among women who underwent labor induction with vaginal dinoprostone (PGE2) insert in a Chinese tertiary maternity hospital.

Material and methods: A retrospective study was conducted in Hubei Maternal and Child Health Hospital. A total of 1656 pregnancies that underwent labor induction with vaginal dinoprostone insert between January and August 2016 were finally included in this study. Data were analyzed using univariate and multivariable regression modeling.

Results: Of 1656 women with PGE2-induced labor at term, 396 (23.91%) gave birth by cesarean section, 1260 (76.09%) had a vaginal delivery among which 921 (55.61%) delivered vaginally within 24?h. Multivariable regression analysis showed that maternal age (p?p?p?=?.009, OR = 0.98, 95%CI 0.96–0.99), and birth weight (p?p?p?p?=?.004, OR = 0.96, 95%CI 0.94–0.99), and birth weight (p?Conclusions: Our findings suggested a vaginal delivery rate of 76.09% when dinoprostone vaginal insert was used for labor induction, which was markedly higher than the overall annual vaginal delivery rate of 65.1% in China during 2014. Maternal age, parity, baseline fetal heart rate, and birth weight were significant factors for vaginal delivery. This study enables us to better understand the efficiency of dinoprostone and the potential predictors of vaginal delivery in dinoprostone-induced labor, which may be helpful to guide the clinical use of dinoprostone and therefore provide better service clinically.     

Umbilical cord prostaglandins in term and preterm parturition

Objective: Prostaglandins (PGs) are considered the universal mediators of parturition. Amniotic fluid PGE₂ and PGF_2α concentrations increase before the onset of spontaneous labor at term, as well as during labor. This study was conducted to determine if the concentrations of umbilical cord PGE₂ and PGF₂α change with advancing gestational age, spontaneous labor at term, and preterm labor (with and without funisitis).

Methods: Umbilical cord (UC) tissue samples were obtained from women (N?=?158) with singleton pregnancies in the following groups: (1) term deliveries without labor (TNL; n?=?20); (2) term deliveries with labor (TIL; n?=?20); (3) spontaneous preterm deliveries (sPTD) with (n?=?20) and without acute funisitis (n?=?20); and (4) preeclampsia without labor (n?=?78). The concentrations of PGs were determined in different locations of the UC. PGE₂ and PGF_2α were measured by specific immunoassays. Non-parametric statistics were used for analysis.

Results: (1) In spontaneous preterm deliveries, the median UC PGE₂ concentration was higher in cases with funisitis than in those without funisitis (233.7?pg/µg versus 87.4?pg/µg of total protein, p?=?0.001); (2) the median UC PGE₂ concentration in sPTD with funisitis was also higher than that obtained from samples who had undergone labor at term (233.7?pg/µg versus 116.1?pg/µg of total protein, p?=?0.03); (3) the UC PGE₂ and PGF_2α concentration increased as a function of advancing gestational age before 36 weeks (PGE₂: ρ?=?0.59, p?<?0.001; PGF_2α: ρ?=?0.39, p?=?0.01), but not after 36 weeks (PGE₂: ρ?=??0.1, p?=?0.5; PGF_2α: ρ?=??0.2, p?=?0.2); (4) the median UC concentrations of PGE₂ and PGF_2α at term was similar in samples obtained from women with and without labor (PGE₂: TNL 133.7?pg/µg versus TIL 116.1?pg/µg of total protein, p?=?0.9; PGF_2α: TNL 8.4?pg/µg versus TIL 8.1?pg/µg of total protein, p?=?0.7); and (5) there was no correlation between UC PG concentration and gestational age at term pregnancy (PGE₂: ρ?=?0.01, p?=?0.9; PGF_2α: ρ?=?0.07, p?=?0.7).

Conclusions: (1) PGE₂ concentrations in the UC are higher in the presence of acute funisitis than in the absence of this lesion; (2) spontaneous labor at term was not associated with a change in the UC concentration of PGE₂ and PGF_2α; and (3) the UC concentrations of PGE₂ and PGF_2α increased as a function of gestational age. We propose that UC PGs act as inflammatory mediators generated in the context of fetal systemic inflammation.     

Effect of vaginal pH on efficacy of the controlled-release dinoprostone vaginal insert for cervical ripening/labor induction

Objective: To evaluate whether vaginal pH alters the efficacy of the controlled-release dinoprostone vaginal insert (Cervidil^®) for cervical ripening/labor induction. Methods: Thirty-four women with an unfavorable cervix undergoing labor induction were enrolled in this prospective, double-blind investigation. Vaginal pH and Bishop score assessments were made by an independent examiner. All women received preinduction with the dinoprostone vaginal insert 10 mg intravaginally for 12 h. Twelve hours later, oxytocin induction initiated according to the standardized protocol and outcome data were collected. Results: Mean (± SD) initial vaginal pH was 4.9 ± 0.5 for the study cohort. No significant differences were noted between women with a high vaginal pH (> 4.5, n = 18) and those with a low vaginal pH (≤ 4.5, n = 16) with respect to maternal age, parity, gestational age, or initial Bishop score. Similarly, Bishop score change over the preinduction interval (3.2 vs. 3.3), time to active labor (28.6 vs. 24.6 h) and time to delivery (33.7 vs. 31.4 h) were not significantly different between the low and the high pH groups, respectively. Linear regression analysis revealed no significant association between vaginal pH and Bishop score change during the preinduction interval, time to active labor, time to complete dilatation, or time to delivery. Conclusion: Vaginal pH does not appear to influence the efficacy of the controlled-released dinoprostone vaginal insert for cervical ripening/labor induction.     

A randomized trial of vaginal prostaglandin E2 gel and dinoprostone vaginal insert for induction of labor at term

Objective: The aim of this study was to determine whether dinoprostone vaginal insert (Cervidil) can ripen the cervix and induce labor more effectively and safely than a hospital-prepared intravaginal gel.Methods: Three hundred thirty-six patients undergoing cervical ripening for induction of labor at term were randomly assigned to receive either Cervidil insert or a hospital-formulated prostaglandin E₂ gel. Bishop scores were evaluated before and after administration of the ripening agent, and charts were subsequently reviewed for labor characteristics, mode of delivery, and complications of labor and delivery.Results: Cervical ripening as measured by a change in Bishop score was significantly better in those patients receiving Cervidil than those receiving the gel (3.54 vs 2.29, P < .0001). Although duration of labor was similar between the two groups, those receiving Cervidil were less likely to require oxytocin stimulation (RR 0.51, 95% CI 0.29–0.91). Though the Cervidil group had a lower cesarean section rate than the gel group, the difference did not achieve statistical significance (25.4% vs 33.8%, P = .089). Complication rates did not differ significantly between the two groups.Conclusions: Cervidil insert is superior to intravaginal gel in ripening the cervix and inducing labor, with no increase in morbidity. It has not been shown to have a significant effect on duration of labor or mode of delivery.     

Early amniotomy after dinoprostone insert used for the induction of labor: a randomized clinical trial

Purpose: We assessed whether early amniotomy, after ripening with a dinoprostone insert, reduces the duration of labor or increases the rate of delivery within the following 24?h.

Methods: A prospective randomized controlled study was conducted on 200 consenting, term pregnant women at the Zeynep Kamil Maternity and Children’s Training and Research Hospital. Each participant received vaginal inserts of 10?mg dinoprostone. The women were randomly assigned to one of two groups: early amniotomy (artificial rupture of membranes when cervical dilation was at 3?cm) or standard amniotomy (the membranes were left to rupture spontaneously). The primary outcome measures were the time from induction to delivery, and the proportion of women who delivered within 24?h.

Results: The median time interval from induction to delivery (13.72?h compared to 22.73?h) was significantly shorter for women who underwent early amniotomy (p?p?Conclusions: Early amniotomy, after ripening with a dinoprostone insert, is a safe and efficient method for speeding up delivery times without increasing caesarian rates during labor inductions.     

Controlled-release dinoprostone insert versus Foley catheter for labor induction: a meta-analysis

Objective: To compare the effectiveness and safety of controlled-release dinoprostone insert with Foley catheter balloon for cervical ripening and labor induction.

Methods: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China Knowledge Resource Integrated Database were searched. Only randomized controlled trials comparing controlled-release dinoprostone insert with Foley catheter balloon were included. Risk ratio (RR) or mean difference (MD) with 95% con?dence interval (CI) was calculated.

Results: Six studies were included with 731 women received dinoprostone insert and 722 Foley catheter. Time from induction to delivery was significantly shortened in dinoprostone insert group compared to Foley catheter group (MD 5.73 h, 95% CI 1.26–10.20). There were no significant differences in vaginal delivery within 24 h (RR 0.75, 95% CI 0.43–1.30) or cesarean section (RR 0.94, 95% CI 0.80–1.12) between two ripening methods. Dinoprostone insert was related with increased rate of excessive uterine contraction (RR 0.07, 95% CI 0.03–0.19), but less oxytocin use (RR 1.86, 95% CI 1.25–2.77) when compared with Foley catheter.

Conclusions: Induction of labor with controlled-release dinoprostone insert seems to be more effective than Foley catheter. However, the former method causes excessive uterine contraction more frequently.     

Outpatient versus inpatient cervical ripening with a slow-release dinoprostone vaginal insert in term pregnancies on maternal,neonatal, and birth outcomes: A systematic review

Backgrounds

Outpatient induction of labor (IOL) is an alternative choice offered to pregnant women requiring cervical ripening. Outpatient IOL can provide solutions in terms of women empowerment, but most importantly promotes as normal labor as possible, within the medical context of the IOL. The objectives of this systematic review were to assess safety and effectiveness of cervical ripening performed with a slow-release dinoprostone vaginal insert in term pregnancies in two settings: the outpatient (home) versus the inpatient (hospital).

Methods

The electronic databases Cinahl, Embase, Medline and Maternity and Infant Care were searched to detect studies that met the inclusion criteria. Both reviewers collected the data and assessed the quality of the studies and assessed the pooled odds ratio using a 95% confidence interval and a random-effects model. Primary outcomes were linked to maternal and neonatal morbidity. Secondary outcomes were related to birth outcomes.

Results

No statistical difference was seen between the outpatient and inpatient setting in terms of maternal complications, neonatal morbidity, cesarean section, and labor onset <24 h. Women in the outpatient setting were significantly less likely to experience uterine hyperstimulation, and they were also significantly more likely to require oxytocin to augment or induce their labor than the women in the inpatient setting. Women in the outpatient setting were more satisfied with the cervical ripening experience.

Conclusions

Cervical ripening with a slow-release dinoprostone vaginal insert in term pregnancies in the outpatient setting appears as safe as the inpatient setting in terms of maternal, neonatal, and birth outcomes.     

Using dinoprostone vaginal insert for induction of labor: A single institute experience

ObjectiveTo evaluate the factors associated with the successful induction of labor (IOL) in women treated with dinoprostone slow-released vaginal insert.Material and methodsA retrospective study was conducted between June 2017 and December 2017, enrolling 65 patients who underwent dinoprostone slow-released vaginal insert-induced labor. The correlation between the characteristics of the pregnant women and its success, as well as perinatal complications and adverse outcomes were analyzed.ResultsFifty-three of 65 (81.5%) achieved a successful vaginal delivery. Only multi-parous pregnant women were an independent predictor factor for successful induction after dinoprostone slow-released vaginal insert, since all of them succeeded after this strategy treatment (100%, n = 18), compared to 74.5% (35/47) of successful rate in the nulliparous pregnant women with a statistically significant difference (p = 0.018). There were no adverse events occurred in both mothers and their offspring.ConclusionDinoprostone slow-released vaginal insert is a good choice for multiparous pregnant women who need IOL, regardless of which reasons are indicated. For nulliparous women, more studies might be needed to evaluate the effectiveness of PGE2 for IOL.     

Labor induction with prostaglandin E1 misoprostol compared with dinoprostone vaginal insert: A randomized trial

Objective: To compare the safety, efficacy, and costs of intravaginal misoprostol versus dinoprostone vaginal inserts for cervical ripening and labor induction.Methods: Two hundred twenty-three labor induction patients were assigned randomly to one of two treatment groups: 1) intravaginal misoprostol or 2) dinoprostone vaginal inserts. Fifty micrograms of misoprostol were placed in the posterior vaginal fornix every 3 hours for a maximum period of 24 hours. Ten milligrams of dinoprostone was administered in a single application as a vaginal insert for 12 hours.Results: Among 223 patients evaluated, 108 were allocated to the misoprostol group and 115 to the dinoprostone group. The median interval from induction to vaginal delivery was significantly shorter in the misoprostol group: 698 (range 395–1053) versus 1041 (range 792–1531) minutes (P < .001). Vaginal delivery within 12 hours of ripening occurred in 40.7% of patients who received misoprostol compared with 19.1% for those receiving dinoprostone (P < .001); no significant difference between the groups was noted for vaginal delivery within 24 hours. Uterine tachysystole occurred more frequently in patients in the misoprostol group (21.3%) than in the dinoprostone group (7.0%) (P = .004). Nevertheless, no statistically significant differences were noted between the groups with respect to intrapartum complications, including uterine hyperstimulation, mode of delivery, and neonatal or maternal adverse outcomes. The average cost per patient for misoprostol treatment was $85 compared with $606 for treatment with the vaginal insert.Conclusion: Intravaginal misoprostol and the dinoprosone vaginal insert appear to be safe agents for cervical ripening and labor induction. However, misoprostol is less expensive and more effective than the dinoprostone vaginal insert.     

Comparing vaginal misoprostol versus Foley catheter plus vaginal isosorbide mononitrate for labor induction

Objective(S): To compare the effectiveness and safety of intra-cervical Foley catheter combined with intra-vaginal isosorbide mononitrate (IMN) versus intra-vaginal misoprostol for cervical ripening and labor induction in pregnant women with unripe cervices.

Methods: Open-labeled randomized controlled trial in Cairo university hospital, Cairo, Egypt during 2012–2014. Three hundred and ninety-five pregnant women at term or post-term with an indication for labor induction and unripe cervix were included in the study. The subjects were randomly divided into two groups. Vaginal misoprostol was used in group 1 (n?=?197) and intra-cervical Foley catheter plus vaginal IMN in group 2 (n?=?198). Our main outcome measure was cesarean section rate.

Results: Among the 395 included patients there were significantly lower duration of induction of labor (p?<?0.001) in group 1with lower cesarean section rates [22.8% in group 1versus 33.3% in group 2; RR 0.7 (0.6–0.9), (p?=?0.020)]. Whereas the uterine hyperstimulation (p?<?0.001) was significantly higher in group 1. There were no significant differences between both groups as regard patients’ demographic characteristics.

Conclusions(s): Vaginal misoprostol is more effective but less safe than Foley catheter combined with vaginal IMN for induction of labor in term and post-term pregnancy.     

A new approach to an old hypothesis; phototherapy does not affect ductal patency via PGE2 and PGI2

Objective: Numerous investigations have demonstrated that phototherapy (PT) directly or indirectly causes ductal patency by photorelaxation effect. In this observational study, we aimed to assess the effect of PT on the incidence of patent ductus arteriosus (PDA) together with prostaglandins (PGE2) and (PGI2) levels in preterm infants.

Methods: Preterm infants whose gestational age?2 and PGI₂ levels were measured before and after PT. The outcome measures were the status of ductus arteriosus and alterations of PGE₂ and PGI₂ levels under the effect of PT.

Results: A total of 44 preterm infants were enrolled in the study, of these 21 (47.7%) were in Group 1 (Non-PDA Group) and 23 (52.3%) were in Group 2 (PDA Group). After PT, ductal reopening occurred in three infants (14.3%) in Group 1, while ductus closed in four infants in Group 2 (17.3%). PT does not seem to effect ductal patency for both groups (p?=?0.250 and p?=?0.125, respectively). PGE₂ levels were not different before and after PT for both groups (p?=?0.087, p?=?0.408, respectively). However, PGI₂ levels were significantly decreased after PT in both groups (p?=?0.006, and p?=?0.003, respectively).

Conclusion: There was no effect of PT on ductal patency. We can conclude that PGs were eliminated simultaneously with ductal closure and photorelaxation effect did not influence PG levels.     

Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-Bishop-score pregnancy

BACKGROUND: Dinoprostone vaginal insert has been compared to Dinoprostone cervical gel in few studies, whose cases presented different Bishop scores and gestational ages at admission, and various treatment strategies in control arms. The present study compares the vaginal insert to the cervical gel in patients with low Bishop score at term. METHODS: Prospective multicenter randomized trial, with parity-based randomization. Admission criteria: single pregnancy with Bishop score of 0-4, gestational age of 37-41 weeks, intact membranes, no previous cesarean section, no bleeding or abnormal cardiotocography at admission. RESULTS: Vaginal prostaglandins were required as a second-line induction procedure in 25% of study patients versus 47.1% of controls (p < 0.03, chi2). Study patients experienced shorter induction-to-delivery time (920 +/- 428 versus 1,266 +/- 740 min, p <0,01), with a mean difference of 5 h and 46 min between the groups. Even though patients that received vaginal insert showed a trend of increased incidence of abnormal cardiotocography during labor (12% versus 6.3%) and hyperkinetic labor (11.8% versus 2.1%), the incidence of cesarean sections (21.4% versus 21.6%), cesareans for fetal distress (12.5% versus 11.8%), and umbilical artery pH <7.10 (4.9% versus 2.5%) was comparable between the two groups. CONCLUSIONS: Dinoprostone vaginal insert is more efficient than cervical gel in promoting cervical priming and labor induction in low-Bishop-score patients at term. The vaginal insert placement seems to be safe for the mother and the newborn, although larger studies are required to investigate uterine hyperstimulation incidence.     

Predictors of successful labor induction with oral or vaginal misoprostol

Objective: To identify independent predictors of successful labor induction with oral or vaginal misoprostol.

Methods: Women enrolled in four previous randomized trials involving oral or vaginal misoprostol for cervical ripening and labor induction were included in the present cohort study, with dosing of 25–50?μg every 4 to 6?h vaginally (n?=?574) or 50?μg every 4?h orally (n?=?207). Multiple logistic regression was performed to identify factors independently associated with successful labor induction – defined as vaginal delivery within 12?h, vaginal delivery within 24?h and spontaneous vaginal delivery. Predictors of Cesarean birth and the need for only one dose of misoprostol were also identified. Variables included in the models were maternal age, weight, height, parity, gravidity, membrane status, route of misoprostol, gestational age, birth weight, and Bishop score and its individual components.

Results: Maternal age, height, weight, parity, birth weight, dilatation, effacement and cervical station were associated with vaginal delivery within 24?h of induction. Maternal age, height, weight, nulliparity, birth weight and route of misoprostol were associated with Cesarean birth, with oral misoprostol being associated with a lower rate of Cesarean birth. The need for only one dose of misoprostol was predicted by maternal height, weight, parity, gestational age, Bishop score and route of misoprostol.

Conclusion: Characteristics of the woman (height, weight, parity), the fetus (birth weight) and some of the individual components of the Bishop score, were associated with successful labor induction, with oral misoprostol being associated with a lower rate of Cesarean birth.     

Induction of labor in women that had a previous cesarean delivery

Objective: This study aims to evaluate factors that predict the likelihood of the success of induction of labor (IOL) in women that had a previous cesarean section (pCS).

Methods: Pregnant women with one pCS performed more than 18 months prior were included in this retrospective observational study. Of the 242 eligible women, 234 were enrolled; 120 (51.3%) of these women delivered vaginally (VD), with the remainder receiving a repeat CS.

Results: The main reasons for IOL were premature rupture of membranes (PROM) (37.1%) and post-date pregnancy (26.5%). Babies with a birth weight ≥4000?g were more prevalent in women undergoing CS (21/114; 18.4%, p?Having had a previous vaginal delivery (VD) (p?=?0.01), not being African (p?=?0.022), and receiving IOL for PROM (p?=?0.04) with a cervical Bishop score ≥5 (p?=?0.015) significantly predicted the occurrence of a VD, with an 15% variance (p?35 years appears to not affect the success of induction.

Conclusions: A successful IOL should be expected in Caucasian women induced for PROM with a favorable Bishop score.     

Misoprostol vaginal insert compared with dinoprostone vaginal insert: a randomized controlled trial

OBJECTIVE: To compare the 50-microgram (misoprostol vaginal insert 50) and 100-microgram (misoprostol vaginal insert 100) dose reservoirs of the misoprostol vaginal insert to 10-mg dinoprostone vaginal insert for time to vaginal delivery and rate of cesarean delivery. METHODS: A total of 1,308 women requiring cervical ripening (modified Bishop score less than or equal to 4) before induction of labor were randomly assigned to receive misoprostol vaginal insert 100 (n=428), misoprostol vaginal insert 50 (n=443) or 10-mg dinoprostone vaginal insert (n=436). The primary outcomes were time to vaginal delivery and rate of cesarean births. Safety was also assessed by comparing frequency of adverse events. RESULTS: Median time to vaginal delivery was 1,596, 2,127, and 1,650 minutes for misoprostol vaginal insert 100, misoprostol vaginal insert 50, and dinoprostone vaginal insert, respectively (P=.97 and 0.01 compared with dinoprostone vaginal insert, respectively). Of those who delivered in first admission, cesarean deliveries occurred in 119 of 421 (28.3%), 124 of 429 (28.9%), and 115 of 424 (27.1%) of participants treated with misoprostol vaginal insert 100, misoprostol vaginal insert 50, and dinoprostone vaginal inserts, respectively (relative risk 1.04, 95% confidence interval 0.84-1.30 for misoprostol vaginal insert 100 and relative risk 1.06, 95% confidence interval 0.86-1.32 for misoprostol vaginal insert 50 compared with dinoprostone vaginal insert). Medication-related adverse events included hyperstimulation syndrome in 17 of 428 (4.0%), 6 of 443 (1.4%), and 21 of 436 (4.8%); and nonreassuring fetal heart rate patterns in 63 of 428 (14.7%), 54 of 443 (12.2%), and 67 of 436 (15.4%) of participants treated with the misoprostol vaginal insert 100, misoprostol vaginal insert 50, and dinoprostone vaginal inserts, respectively. CONCLUSION: The misoprostol vaginal insert 100 and the dinoprostone vaginal insert had similar median time intervals to vaginal delivery, whereas the misoprostol vaginal insert 50 had a significantly longer time to vaginal delivery. The three products had similar cesarean rates and safety profiles.     

Oral versus vaginal prostaglandin for labor induction

Objective: To compare the efficacy and safety of oral prostaglandin (PG) in solution versus vaginal PG gel for labor induction.

Design: A retrospective study.

Methods: Data from original obstetric records at a university hospital in Sweden 2012–2013.

Results: In all women, oral PG resulted in vaginal birth (VB)?p?p?=?0.02). In primiparous women, oral PG was followed by VB <24?h in 54% compared to 71% (p?=?0.01), and CS in 25% versus 41% (p?=?0.03). In women with an unripe cervix, oral PG lead to VB <24?h in 66% compared to 79% (p?=?0.01), and CS in 21% versus 33% (p?=?0.04). Despite a longer induction to vaginal delivery interval with oral PG, the rates of obstetric bleeding, chorioamnionitis, and neonatal asphyxia were not increased.

Conclusions: Oral PG in solution was less effective than vaginal PG gel in achieving VB <24?h. However, oral PG was safer, since it resulted in fewer CSs without increasing maternal morbidity or neonatal asphyxia.     

Determining dose and endpoints of a controlled-release misoprostol vaginal insert for a phase III trial

OBJECTIVE: To determine phase III study design using the phase II data for a proprietary controlled-release misoprostol vaginal insert for cervical ripening and labor induction. METHODS: The reported experiences in 2 phase II trials involving induction of labor in 168 women are discussed. RESULTS: Combining data from 2 phase II studies, we reported a median induction to vaginal delivery interval of <15 hours regardless of parity using the 100-microg insert. This misoprostol vaginal insert was well tolerated with few maternal systemic effects. Uterine hyperstimulation occurred in <5% of cases in the 100-microg and lesser dose groups. Hyperstimulation syndrome attributed to insert led to cesarean delivery in 1 (2.4%) subject in the 200-microg and 2 (33.3%) in the 300-microg dose groups. The lowest cesarean rates were 4.7% (2 of 43) in the 100-microg group and 5.7% (2 of 35) in the 50-microg group. CONCLUSION: Misoprostol vaginal 50-microg and 100-microg inserts had acceptable efficacy and safety profiles, and we agreed to test these doses in a randomized phase III multicenter study using dinoprostone (Cervidil, Forest Pharmaceuticals, St. Louis, Missouri), a dinoprostone vaginal insert, as the blinded comparator.     

Comparative efficacy and safety of vaginal misoprostol versus dinoprostone vaginal insert in labor induction at term: a randomized trial

Objective  To compare efficacy and safety of vaginal misoprostol (PGE₁ analog) with dinoprostone (PGE₂ analog) vaginal insert for labor induction in term pregnancies. Study design  A total of 112 women with singleton pregnancies of ≥37 weeks of gestation, and low Bishop scores underwent labor induction. The subjects were randomized to receive either 50 μg misoprostol intravaginally every 4 h to a maximum of five doses or a 10 mg dinoprostone vaginal insert for a maximum of 12 h. Time interval from induction to vaginal delivery, vaginal delivery rates within 12 and 24 h, requirement of oxytocin augmentation, incidence of tachysystole and uterine hyperstimulation, mode of delivery, rate of cesarean section due to fetal distress and neonatal outcome were outcome measures. Student’s t test, Chi square test, Fischer’s exact test were used for statistical analysis. Results  Time interval from induction to vaginal delivery was found to be significantly shorter in misoprostol group when compared to dinoprostone subjects (680 ± 329 min vs. 1070 ± 435 min, P < 0.001). Vaginal delivery rates within 12 h were found to be significantly higher with misoprostol induction [n = 37 (66%) vs. n = 25 (44.6%); P = 0.02], whereas vaginal delivery rates in 24 h did not differ significantly between groups [n = 41 (73.2%) vs. n = 36 (64.2%); P = 0.3]. More subjects required oxytocin augmentation in dinoprostone group [n = 35 (62.5%) vs. n = 20 (35.7%), P = 0.005] and cardiotocography tracings revealed early decelerations occurring more frequently with misoprostol induction (10.7 vs. 0%, P = 0.03). Tachysystole and uterine hyperstimulation, mode of delivery, rate of cesarean sections due to fetal distress and adverse neonatal outcome were not demonstrated to be significantly different between groups (P = 1, P = 0.5, P = 0.4, P = 0.22, P = 0.5). Conclusion  Using vaginal misoprostol is an effective way of labor induction in term pregnant women with unfavorable cervices, since it is associated with a shorter duration of labor induction and higher rates of vaginal delivery within 12 h. Misoprostol and dinoprostone are equally safe, since misoprostol did not result in a rise in maternal and neonatal morbidity, namely, tachysystole, uterine hyperstimulation, cesarean section rates and admission to neonatal intensive care units as reported previously in literature.