An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term.

The purpose of this randomized, double-blind study was to evaluate the efficacy and safety of a new controlled-release hydrogel pessary for ripening the cervix and initiating labor. Subjects had an entry Bishop score of 4 or less and gestational age of 37 or more weeks. One hundred fourteen women received a placebo pessary and 101 received the hydrogel pessary, containing 10 mg of prostaglandin (PG) E2. Compared with the placebo group, those given the PGE2 pessary were more likely to have an increase in Bishop score of 3 or more (60 or 59% versus 21 or 18%; P less than .0001), change to a Bishop score of 6 or higher (59 or 58% versus 18 or 16%; P less than .0001), and active labor (68 or 67% versus 15 or 13%; P less than .0001). Including the crossover study, uterine hyperstimulation (28 of 182, 15%) and fetal heart rate abnormalities (18 of 182, 10%) in PGE2-treated subjects were reversed on removal of the pessary with no apparent harm to the mother or fetus. These temporary adverse effects appeared while the pessary was in place and after the onset of active labor. Oxytocin was unnecessary in 89 of 182 (49%) of the PGE2-treated cases and was used more often to augment than to induce labor. We conclude that the described controlled-release PGE2 vaginal pessary induces appreciable cervical ripening and frequently initiates active labor with little or no need for oxytocin. The pessary may cause uterine hyperstimulation or fetal heart rate abnormalities, but these would be expected to reverse on removal of the pessary.     

Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction

Twelve pregnant women at term with unfavorable cervices (less than or equal to 5 points according to Bishop score) were given prostaglandin E2 for cervical priming and labor induction. Prostaglandin E2 was given in the following manner: 0.5 mg in gel strictly intracervically (n = 4), extraamniotically (n = 4), or prostaglandin E2 (4 mg) in gel vaginally (n = 4). The myometrial activity was registered over a period of 30 minutes before and at least 3 hours after gel application by means of an extraamniotic microtransducer catheter. After both extraamniotic and vaginal gel application, myometrial activity was significantly increased compared with intracervical application. All the women had favorable cervical states 6 hours after treatment and were delivered vaginally within 24 hours. All infants were delivered in good condition with 1-minute Apgar scores greater than 7. From these results we conclude that proper intracervical prostaglandin E2 gel application, in contrast to extraamniotic or vaginal application, induces cervical ripening without significant myometrial activity. Because careful intracervical application appears to avoid or minimize the risks of myometrial hyperstimulation, this technique should be considered particularly in women with unfavorable cervices and delicate fetuses.     

Prediction of cervical response to prostaglandin E2 using fetal fibronectin

BACKGROUND: To determine whether presence of fetal fibronectin in cervico-vaginal secretions at term will predict the cervical response to prostaglandin E2 (PGE2) pessaries and successful induction of labor amongst subjects with unfavorable cervices. METHODS: Cervico-vaginal secretion was tested for the presence of fetal fibronectin prior to cervical ripening with PGE2 pessaries in women with a singleton term or post-term pregnancy undergoing induction of labor. The total number of PGE2 pessaries, interval from induction to labor and induction to delivery, latent phase and active phase of labor and cesarean section rate were compared. RESULTS: Women with fetal fibronectin in their cervico-vaginal secretion had better cervical response to PGE2 pessaries and required fewer doses for induction of labor and they took a shorter time interval from induction to delivery. They tend to have a lower cesarean section rate but the figures did not reach statistical significance. CONCLUSIONS: The presence of fetal fibronectin from cervico-vaginal secretions in subjects with a Bishop score <5 is predictive of a favorable response to induction by prostaglandin pessary     

Preinductive cervical ripening with prostaglandin E2 in women with one previous cesarean section.

Thirty term pregnant women with one previous cesarean section and with unripe cervices were given 0.5 mg prostaglandin E2 in gel strictly intracervically for cervical ripening and labor induction. Fifteen out of these 30 women (50%) were vaginally delivered within 24 hours. The cervical ripening/labor induction was considered a failure in two women. In one woman, an episode of hypercontractility was registered. After tocolytic therapy the uterine activity was normalised and the woman had a normal vaginal delivery. The frequency of cesarean sections was 8/30 (27%). At the operations no insufficiencies in the uterine scars were noted. Conclusively, strict intracervical application of 0.5 mg prostaglandin E2 in gel can be used for cervical ripening and labor induction also in women with one previous cesarean section.     

Induction of labor by vaginal prostaglandin E2. A randomized study comparing pessaries with vaginal tablets.

A prospective randomized study of 267 pregnant women was undertaken to compare the efficacy of a pharmacy-prepared 3-mg prostaglandin E2 (PGE2) vaginal suppository with a 3-mg PGE2 vaginal tablet for induction of labor and cervical ripening. No statistically significant difference in success frequency was found between the two groups, either on the first day (72% and 74%, respectively; p greater than 0.05) or on the second day (89% in both groups). There was an equal proportion of women requiring oxytocin augmentation in the two groups, but the slower releasing properties of the vaginal tablet were reflected in a longer mean induction--delivery interval of about 4 h for this group. In both the pessary and the vaginal tablet groups, women who had not gone into labor on the first day showed a statistically significant increment in the Bishop score on the morning of the second day. The frequency of cesarean section was the same in both groups, but instrumental deliveries were more frequent in the vaginal tablet group. It is concluded that PGE2 vaginal tablets--a chemically stable alternative to pharmacy prepared pessaries--appear to be effective as regards cervical ripening as well as for labor induction.     

Uterine rupture after use of a prostaglandin E2 vaginal insert during vaginal birth after cesarean. A report of two cases.

BACKGROUND: Prostaglandin E2, when used for cervical ripening, often initiates labor. Single dosing and ease of removal contribute to the common use of a commercially available prostaglandin E2 vaginal insert. We describe two cases of uterine rupture among 57 pregnancies undergoing attempted vaginal birth after cesarean section. CASES: Two cases of women attempting vaginal birth after a single low transverse cesarean section were treated with the insert either at 41 weeks, 4 days, or 39 weeks, 3 days, for postdatism or preeclampsia. Signs of uterine rupture included persistent suprapubic pain and repetitive fetal heart rate variable decelerations followed by bradycardia. Infant outcomes were favorable, and tears along the prior low transverse uterine scar were repaired without additional morbidity. CONCLUSION: This prostaglandin compound is not exempt from being associated directly or indirectly with uterine rupture and requires informed consent and continuous monitoring.     

Induction of labor and pain: a randomized trial between two vaginal preparations of dinoprostone in nulliparous women with an unfavorable cervix

Objective.?To compare pain associated with vaginal dinoprostone pessary vs. gel for induction of labor in women with an unfavorable cervix.

Study design.?A randomized controlled trial in a large academic public general hospital. A total of 52 nulliparous women of gestational age?≥38 weeks, with Bishop score?≤4 and intact membranes were allocated either to a controlled-release vaginal dinoprostone pessary or repeat doses of vaginal dinoprostone gel. Pain was recorded hourly from early induction until the onset of labor.

Results.?Mean pain experienced by women belonging to the two groups differed significantly (p?<?0.01). Women in the controlled-release device group were also significantly more often severe pain-free than women receiving gel (p?<?0.05). Both methods had similar rates of oxytocin infusion and vaginal deliveries.

Conclusions.?The two induction procedures should be considered equivalent as far as ripening the cervix and initiating labor. In view of this finding, the low Bishop score should be considered an indication to prefer the controlled-release device, since it reduces pain thereby improving the physical and emotional wellbeing of the parturient.     

Prostaglandin: cervical ripening in hypertensive pregnancies

BACKGROUND: To determine the outcome of cervical ripening with intracervical prostaglandin E2 (PEG2) in hypertensive and non-hypertensive high-risk pregnancies in terms of successful ripening, mode of delivery, time intercorring between ripening and the beginning of labor or parturition and, at least, duration of labor. METHODS: A total of 63 women with a diagnosis of hypertensive disorders were included in the study protocol. These 63 women were compared with 71 consecutive high-risk pregnancies requiring induction of labor for maternal and/or fetal indications. Cervical ripening was performed with single or multiple doses of 0.5 mg of intracervical PGE2 gel. RESULTS: The rate of successful ripening was 84% for non-hypertensive patients (60/71) and 69% (43/63) for hypertensive patients ( p < 0.03). Twenty-four out of 63 hypertensive patients (38%) and 21 out of 71 non-hypertensive patients (30%) ( p < 0.05) were delivered by cesarean section. After stratification of hypertensive patients, the time interval from the first PGE2 administration to the onset of labor or vaginal delivery was significantly longer for preeclamptic patients vs. non-hypertensive patients or non-preeclamptic hypertensive patients. There were no differences in the duration of labor. CONCLUSIONS: Among hypertensive patients, only preeclamptic patients showed a lower rate of successful ripening and vaginal delivery if compared with non-preeclamptic or non-hypertensive patients; however, a vaginal delivery might be obtained in most preeclamptic patients when suitable cervical ripening was performed in the presence of clinician-perceived urgency to delivery.     

Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis

Objective: To compare dinoprostone 10 mg controlled-release vaginal insert with other forms of vaginal or cervical prostaglandin for cervical ripening.Data Sources: Literature search strategy included review of the Cochrane database of randomized trials, on-line searching of MEDLINE, hand searching of bibliographies, and contact with authors of relevant reports.Methods of Study Selection: Randomized trials were included if they compared a dinoprostone slow-release vaginal insert with an alternative vaginal or cervical prostaglandin for cervical ripening and labor induction in women at term with singleton gestations. Primary end points were delivery by 24 hours postinsertion, uterine hypertonus with fetal heart change, and cesarean delivery rate. Study inclusion, validity assessment, and data extraction were carried out independently by two reviewers, and cross-checked for consistency. Data were combined when appropriate, using the Mantel–Haenszel fixed-effects method. Statistical heterogeneity was assessed using chi-square statistics.Tabulation, Integration, and Results: Nine relevant trials were identified, seven comparing the dinoprostone 10 mg vaginal insert with dinoprostone gel and two with misoprostol. Five trials reported adequate methods for randomization concealment. None were double blind. The likelihood of delivery by 24 hours was similar with the vaginal insert and alternatives: common odds ratio (OR) 0.80 (95% confidence interval [CI] 0.56, 1.15). Uterine hypertonus with change in fetal heart and cesarean delivery rate were also similar: common OR 1.19 (95% CI 0.56, 2.54) and 0.78 (95% CI 0.56, 1.08), respectively. The secondary end points of mean time to delivery and delivery by 12 hours appeared to favor misoprostol-dinoprostone gel. However, data for these end points were heterogeneous and their combination is therefore of limited value and potentially misleading.Conclusion: No clinically significant differences were identified between the vaginal insert and alternatives used for cervical ripening at term.     

Obstetric outcomes after cervical ripening by multiple doses of vaginal prostaglandin E2

AIM: The study was designed to investigate the delivery outcome in women who required vaginal prostaglandin E2 for cervical priming prior to labor induction. MATERIALS AND METHODS: This retrospective cohort study included all singleton term deliveries that required labor induction over a 3-year period. Incidence and indications of obstetric interventions were compared among women who required different doses of vaginal prostaglandin E2 for cervical priming and who had induction by amniotomy and oxytocin infusion. RESULTS: Of 706 deliveries, 411 had favorable Bishop's scores and no vaginal prostaglandin E2 for cervical priming was required (group A); 268 required one or two doses of vaginal prostaglandin E2 for cervical priming (group B); and 27 required three or more doses (group C). The incidence of cesarean section was significantly higher in group C (48.1%) than in group A (19.0%) and group B (16.4%). The difference remained statistically significant when primiparous and multiparous women were analyzed separately. The risk of obstetric intervention was particularly high in primiparous women in group C (58.8% required emergency cesarean section and 23.5% had instrumental delivery). There was an increased frequency of all major indications for cesarean section in group C. CONCLUSION: The risk of emergency cesarean section was higher in women who required more than two doses of vaginal prostaglandin E2 for cervical priming compared to induction by one or two doses of vaginal prostaglandin E2 or by amniotomy and oxytocin infusion. These women should be informed regarding the high risk of intrapartum cesarean section, and the option of alternative methods of induction or elective cesarean section should be made available.     

Extra-amniotic Foley catheter and prostaglandin E(2) gel for cervical ripening at term gestation.

OBJECTIVE: This study evaluated the efficacy of intravaginal prostaglandin E(2) gel in comparison with that of a Foley catheter for cervical ripening and induction of labor. STUDY DESIGN: Consecutive patients with unfavorable cervix requiring preinduction cervical ripening and induction of labor at term gestation were asked to participate in the study. One hundred and two patients were assigned to treatment with intravaginal prostaglandin E(2) gel (group 1) and 122 patients underwent the placement of an intracervical Foley catheter (group 2). After a maximum of three applications of intravaginal prostaglandin E(2) gel (18h) or after 18h from Foley catheter insertion oxytocin was administered to patients not in active labor. Labor profiles and pregnancy and neonatal outcome were compared between groups. RESULTS: The groups were comparable in term of demographic characteristics, indications for induction of labor, Bishop score at admission. The induction to labor time and the induction to delivery time were similar between groups. The cesarean sections rate was higher in group 1 than in group 2 (26.5 versus 14.7%, P<0.05). This remained significant when the analysis was restricted to nulliparous patients (32.3 versus 14.2%). The incidence of urinary tract infections, chorioamnionitis, and febrile morbidity was similar between groups. CONCLUSION: For preinduction cervical ripening, the Foley catheter is a valid alternative to the application of intravaginal prostaglandin E(2) gel and it is associated with a lower cesarean rate in nulliparous women.     

Use of prostaglandin E2 topical cervical gel in high-risk patients: a critical analysis

This investigation compared the safety and efficacy of 3- and 5-mg doses of prostaglandin E2 topical gel used for cervical ripening in 60 high-risk obstetric patients before oxytocin induction of labor. Both dosages significantly increased the Bishop score, unrelated to parity or gestational age. Induction time was significantly shortened, and the average maximum amount of oxytocin required was significantly less with the 5-mg dose, but not with the 3-mg dose, when compared with a placebo. Prostaglandin E2 did not influence the cesarean section rate. Uterine contractions were stimulated in 87.5% of the patients who received the drug, and 37.5% went into active labor, suggesting that prostaglandin E2 in these dosages is not an appropriate agent for local cervical ripening.     

A comparison of three dosages of prostaglandin E2 pessaries for ripening the unfavourable cervix prior to induction of labor

A study was planned to evaluate the effect of Prostaglandin E2 pessaries in three different dosages in ripening the unfavourable cervix prior to the induction of labor. A single dose of PGE2 as pessary in the three different dosages was administered into the posterior vaginal fornix to ripen an unfavourable cervix with a Bishop score less than or equal to 4 in 101 primigravid and 79 multigravid patients. The pessary containing 2 mgm was as effective as 3 mgm and 5 mgm PGE2 pessary in ripening the cervix, and the outcome of labor and fetal status were similar with the different dosages of PGE2. However, two multigravid patients who received 5 mg of PGEs pessary and one multigravid patient who received 3 mg of PGE2 pessary developed hypertonic uterine activity. None of the patients who received 2 mg PGE2 pessary developed any adverse effect on uterine activity.     

欣普贝生用于足月胎膜早破低宫颈评分引产的效果观察

目的:探讨欣普贝生(地诺前列酮栓)在足月胎膜早破初产孕妇中应用的安全性及有效性。方法:100例足月胎膜早破单胎孕妇,破膜2h后未临产,宫颈条件未成熟(宫颈Bishop评分≤4分),孕妇知情同意后欣普贝生组入组50例,催产素组50例。比较两组的分娩方式及母儿结局情况。结果:与催产素组比较,欣普贝生组8h、12h促宫颈成熟总有效率明显增加(92.0%vs 64.5%,P0.01;95.9%vs 79.2%,P0.05)。欣普贝生组阴道分娩率明显升高(86.0%vs 60.0%,P0.01),且欣普贝生组用药12h、24h内阴道分娩率亦显著提高(42.0%vs 8.0%,P0.001;64.0%vs 34.0%,P0.01)。欣普贝生组用药至临产、用药至阴道分娩时间明显短于催产素组[(7.4±1.0)h vs(14.2±2.0)h,P0.01;(15.4±1.4)h vs(21.4±1.6)h,P0.01]。欣普贝生组引产失败率、绒毛膜羊膜炎发生率显著降低(2.0%vs 16.0%,P0.05;0 vs 12.0%,P0.05);两组急产、胎儿宫内窘迫、相对性头盆不称发生率无明显统计学差异;两组均无产后出血、新生儿窒息。结论:足月胎膜早破且宫颈条件未成熟的初产孕妇,应用欣普贝生促宫颈成熟安全、有效,且效果优于直接催产素引产,但用药期间应加强母儿监护。     

Uterine rupture and dehiscence associated with intravaginal misoprostol cervical ripening

OBJECTIVE: To evaluate if the prostaglandin E1 analogue misoprostol, when used as an agent for cervical ripening, is associated with uterine rupture. STUDY DESIGN: We performed a two-year retrospective chart review to determine the incidence of uterine rupture in patients with a previous cesarean delivery undergoing cervical ripening or the induction of labor. RESULTS: Uterine dehiscence occurred in 1 and uterine rupture occurred in 3 of 48 women with a prior cesarean delivery treated with 50 micrograms doses of intravaginal misoprostol for cervical ripening. Uterine rupture was found in 1 of 89 women who had an oxytocin infusion for induction of labor and none of the 24 patients who received intravaginal prostaglandin E2 placed for cervical ripening. CONCLUSION: Intravaginal misoprostol appears to be associated with an increased incidence of uterine rupture when used in patients undergoing a trial of labor after cesarean.     

Effect of prostaglandin E2 for cervical priming on fetal hemodynamics

OBJECTIVE: To assess the effect of the prostaglandin E2 (PGE2) on fetal vascular blood flow during cervical priming. STUDY DESIGN: In a prospective, observational study, 32 pregnant women > or =37 weeks of gestation requiring PGE2 for induction of labor were recruited. The resistance indices (RIs) of umbilical artery, middle cerebral artery, renal artery and ductus venosum were measured before, 2 and 4 hours after insertion of a PGE2 vaginal pessary. RESULTS: There were no significant changes in RIs of various fetal vessels during cervical priming with PGE2. CONCLUSION: There was no significant change in fetal hemodynamics after vaginal prostaglandin administration. This finding provides further evidence to support the safety of prostaglandin for normal fetuses.     

A META-ANALYSIS OF CONTROLLED-RELEASE PROSTAGLANDIN FOR CERVICAL RIPENING AND LABOUR INDUCTION

OBJECTIVES: to examine the effectiveness and safety of controlled-release prostaglandin for cervical ripening. DATA SOURCES: we conducted a computerized search of Medline using the keywords "Cervidil"; or "Propess"; or "prostaglandin/dinoprostone" and "pessary"; or "prostaglandin/dinoprostone" and "controlled" and "release"; or "prostaglandin/dinoprostone" and "vaginal" and "insert"; identifying studies in the English literature published between January 1980 and December 1999. STUDY SELECTION: we included all randomized trials that compared controlled-release vaginal prostaglandin with a retrieval string with any other method of cervical ripening or with a placebo. Nine studies were identified.TABULATION, INTERACTION, AND RESULTS: the two coauthors independently abstracted the data and evaluated the studies for methodologic quality, blinded to each other's results. Homogeneity of results was evaluated, and if present, the summary odds ratio and 95 percent confidence intervals were determined. Compared with placebo, controlled-release prostaglandin resulted in cervical change (summary odds ratio [OR] = 3.99, 95% confidence interval [CI] = 2.71-5.86), a higher rate of vaginal delivery in 12 hours (OR = 29.01, 95% CI = 7.08-118.87), less need for oxytocin (OR = 0.14, 95% CI = 0.06-0.32), but a higher incidence of excessive uterine activity (P<0.0001) and hyperstimulation (P = 0.004). When compared with Prepidil, there was a higher rate of excessive uterine activity with controlled-release prostaglandin (P = 0.03), but less need for oxytocin (OR = 0.09, 95% CI = 0.01-0.53). When compared with Prepidil/immediate oxytocin, there was a lower rate of active labour in 12 hours with controlled-release prostaglandin (OR = 0.27, 95% CI = 0.10-0.72). There was a lower rate of vaginal delivery in 12 hours and higher incidence of oxytocin use with controlled-release prostaglandin as compared with misoprostol (OR = 0.53, 95% CI = 0.34-0.83 and OR = 1.58, 95% CI = 1.08-2.32 respectively). The induction to delivery interval was shorter with controlled-release prostaglandin than with placebo or Prepidil, but longer than with Prepidil/immediate oxytocin, or misoprostol. Although no differences were seen with maternal morbidity (such as Caesarean delivery) or neonatal outcomes, the sample size was not adequate to evaluate these outcomes. CONCLUSION: controlled-release prostaglandin appears to be an effective cervical ripening agent as compared with Prepidil, but may result in an increased incidence of excessive uterine activity. Controlled-release prostaglandin may not be as effective as misoprostol or Prepidil/immediate oxytocin. Further randomized trials with larger sample sizes are needed to evaluate maternal morbidity and neonatal outcomes.     

Randomized comparison of glyceryl trinitrate and prostaglandin E2 for cervical ripening at term

OBJECTIVE: To estimate the adverse effects of glyceryl trinitrate compared with prostaglandin (PG) E2 vaginal tablet for cervical ripening in term pregnancy. METHODS: One hundred ten women with term pregnancies referred for induction of labor with Bishop scores of 6 or less were randomly assigned to receive a 500-microg glyceryl trinitrate tablet vaginally (n = 54) or a 3-mg PGE2 tablet vaginally (n = 56), every 6 hours for maximum of two doses. Subjects were sent to the labor ward for amniotomy or oxytocin if their Bishop scores were more than 6 or their cervices were not ripe 24 hours after treatment. Adverse effects, changes in the Bishop scores, progress, and outcomes of labor were assessed. RESULTS: Glyceryl trinitrate was associated with fewer episodes of uterine tachysystole (0% versus 9%; P =.02). The median Bishop score after 12 hours was lower in women given glyceryl trinitrate compared with those given PGE2. Adverse effects, including headache and palpitations, were more frequent with glyceryl trinitrate than with PGE2. The cesarean rate was not significantly different between groups. CONCLUSION: Cervical ripening with glyceryl trinitrate resulted in fewer episodes of tachysystole, but there were significantly more minor side effects. It can be used for cervical ripening at term, but it was not as effective as PGE2.     

Evaluation of controlled-release dinoprostone Propess for labor induction

OBJECTIVE: To evaluate the efficacy of cervix ripening with vaginal controlled-release Propess. PATIENTS AND METHODS: A retrospective study of all women who underwent cervical ripening with Propess during the study period from 1(st) January 2002 to 31(st) December 2004 was carried out. A total of 130 patients who experienced Propess was compared with the next following patient who delivered spontaneously matched on gestational age. Modes of delivery, failure of labor, maternal morbidity were recorded. RESULTS: Indications for induction of labor were: post-term pregnancies in 18.5%, pre-eclampsia in 20.8%, oligohydroamnios in 18.5%, post-term pregnancy and oligohydramnios in 10.8%, intra-uterine fetal growth in 6.9%, premature rupture of membranes in 6.9%, diminution of fetal mobility in 6.1% and miscellaneous in 11.5%. Failure of cervical ripening was 21.2%. Patients in the Propess group had a 3.5 fold higher risk of Cesarean section [95% CI: 1.5-8.3; P < 0.04]. There was no case of maternal or fetal death. There was no difference in incidence of maternal complications, and post-partum haemorrhage. DISCUSSION AND CONCLUSION: Use of vaginal pessary Propess does not induce adverse maternal or fetal morbidity. However, it was associated with a higher incidence of Cesarean delivery.     

Uterine and fetal Doppler flow changes after intravaginal prostaglandin E2 therapy for cervical ripening.

Nineteen patients received prostaglandin E2 as a 2.5 mg gel (seven cases), 3.3 mg chip (five cases), or 10 mg controlled-release pessary (seven cases) for preinduction cervical ripening. Blood flow velocities did not change significantly for the uterine arcuate artery, fetal aorta, and umbilical artery circulations after any of the treatments. In no case did systolic/diastolic ratios consistently elevate above baseline values.