Outpatient cervical ripening with prostaglandin E2 gel in uncomplicated postdate pregnancies. Cervical ripening with intravaginal prostaglandin E2 gel. Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome. Premature rupture of membranes in nulliparas at term with unfavorable cervices: a double-blind randomized trial of prostaglandin and placebo. Prolonged pregnancy: the management debate. Randomised trial of outpatient induction of labor with vaginal PGE2 at 40-41 weeks of gestation versus expectant management. Endocervical prostaglandin E2 gel for preinduction cervical softening. A randomized trial of two preparations of vaginal prostaglandin for pre-induction cervical ripening. Is induction of labor indicated in prolonged pregnancy? Results of a prospective randomised trial. A comparison of prostaglandin E2 gel and prostaglandin F2 alpha gel for preinduction cervical ripening. Patient-administered outpatient intravaginal prostaglandin E2 suppositories in post-date pregnancies: a double-blind, randomized, placebo-controlled study. Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. Cervical ripening: a randomized study comparing prostaglandin E2 gel to prostaglandin E2 suppositories. Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial. Outpatient management of the uncomplicated postdate pregnancy with intravaginal prostaglandin E2 gel and membrane stripping. A double blind dose trial of intravaginal prostaglandin F2 alpha for cervical ripening and the induction of labour. A randomized trial of prostaglandin E2 in a controlled-release vaginal pessary for cervical ripening at term. A simpler approach to labor induction using lipid-based prostaglandin E2 vaginal suppository. The induction of labour with prostaglandin E2 tablets administered intravaginally. Improved intravaginal controlled-release prostaglandin E2 insert for cervical ripening at term. The Prostaglandin E2 insert Study Group. Double-blind comparison of intravaginal prostaglandin E2 gel and "chip" for preinduction cervical ripening. Intravaginal prostaglandin E2 for cervical ripening and initiation of labor. Comparison of a multidose gel and single, controlled-release pessary. Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix. An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term. Induction of labour at term with vaginal prostaglandins preparations: a randomised controlled trial of Prostin vs Propess. Maternal plasma bicycling PGE2 levels following vaginal administration of prostaglandin E2 pessaries in full term pregnancies. Patterns of uterine activity after intravaginal prostaglandin E2 during preinduction cervical ripening. Induction of labour: a comparison of two methods with particular concern to patient acceptability. Vaginal administration of PGE2 for induction of labor stimulates endogenous PGF2 alpha production. Cervical ripening with intravaginal prostaglandin E2 gel. Induction of labor by vaginal prostaglandin E2. A randomized study comparing pessaries with vaginal tablets. Is propess a better method of induction of labour in nulliparous women. A comparison of single prostaglandin E2 vaginal tablet with prostaglandin E2 vaginal pessaries for induction of labor at term. Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2. Role of prostaglandin in the management of prelabour rupture of the membranes at term. Prelabour rupture of the membranes at term and unfavourable cervix; a randomized placebo-controlled trial on early intervention with intravaginal prostaglandin E2 gel. A randomized trial of vaginal prostaglandin E2 for induction of labor. Insert vs. tablet. Use of vaginal prostaglandin gel before induction of labour. Comparison of Dinoprostone slow release pessary (Propess) with gel (Prostin) for induction of labour at term-a randomised trial. A comparison of PGE2 and PGF2 alpha vaginal gel for ripening the cervix before induction of labour. Premature rupture of membranes at term with an unfavorable cervix: comparison of expectant management, vaginal prostaglandin, and oxytocin induction. The effect of vaginal administration of various doses of prostaglandin E2 gel on cervical ripening and induction of labor. Local administration of prostaglandin E2 for cervical ripening and labor induction: the appropriate route and dose.
A double-blind, placebo-controlled, prospective investigation was undertaken to determine whether the outpatient administration of prostaglandin E2 gel was helpful for ripening the cervix in postdate pregnancies. One hundred eighteen women with an uncomplicated pregnancy at or beyond 42 weeks' gestation with an unripe cervix (Bishop score less than or equal to 5) were randomly administered a single dose of gel containing either 2.5 mg prostaglandin E2 (n = 55) or a placebo (n = 63) before induction of labor with Pitocin. No side effects were detected in these healthy mothers and fetuses. A distinct change in Bishop score after 12 hours occurred more often in the prostaglandin E2 than in the placebo group (42% versus 6%, p less than 0.0001). Forty-four women (80%) who had received prostaglandin E2 were admitted in early labor; they required little or no oxytocin for augmentation. The duration of labor and maximum dose of oxytocin infused were significantly decreased in the prostaglandin E2 group, and forceps delivery or primary cesarean sections were performed less often when prostaglandin E2 was used (24% versus 44%, p less than 0.05). The outpatient administration of a single dose of prostaglandin E2 gel is safe in the uncomplicated postdate pregnancy and was found to significantly change the unripe cervix, enhance the onset of labor, minimize the need for oxytocin administration, and encourage a spontaneous vaginal delivery. Ripening of the cervix by intravaginal application of a prostaglandin-containing gel is evaluated. Thirty patients with an unfavorable cervix needing labor induction were studied in a double-blind, prospective fashion. The prostaglandin gel proved superior to placebo in ripening the cervix (P less than .05), reducing induction failures (P less than .025), diminishing the oxytocin dosage necessary for induction (P less than .05), and lowering the rate of cesarean section (.05 less than P less than .1). One hundred fifty additional patients with varying Bishop scores and differing clinical situations were also studied. There were 35 cesarean sections (23.3%), nine failed inductions (6%), a spontaneous labor rate of 46%, and an average Bishop score change of 2.5. Twenty patients with premature rupture of the membranes and an unfavorable cervix received a modified gel containing 2.5 mg of prostaglandin E2. Average Bishop score change was 2.9, and there was a 55% incidence of spontaneous labor. To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel.
                Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention.
                A maternity unit in a district general hospital annually delivering > 6000 women.
                Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins.
                Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth.
                For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit.
                There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen. To determine whether the use of a prostaglandin (PG) E2 3-mg pessary followed by a delay of 12 hours before stimulation of labor with oxytocin improves obstetric outcome compared with the use of a placebo pessary.
                One hundred fifty-five nulliparas at term with poor cervical scores (modified Bishop score below 6 of 10) and premature rupture of membranes (PROM) were recruited for this double-blind, placebo-controlled randomized trial. On admission to the study, either a PGE2 pessary or an identical-appearing placebo pessary was inserted into the posterior fornix. If labor did not start in the next 12 hours or if symptoms and signs of infection were evident, labor was induced with oxytocin infusion. Assignment was unblinded at the end of the study, and details of the labor and maternal and neonatal outcome in women who received a PG pessary were compared with those who received a placebo pessary.
                Women receiving a PG pessary were significantly less likely to require stimulation of labor at the end of 12 hours than were those given a placebo pessary (37 versus 58%, P = .002). The mean time between admission to study and delivery was significantly shorter in the PG group compared with the placebo group (15 versus 19 hours, P = .01). The rate of cesarean delivery was not statistically different in the two groups (13.9% with PG versus 15.8% with placebo).
                In nulliparas with poor cervical scores who present with PROM at term and no evidence of infection or obstetric complications, use of a PGE2 pessary resulted in more women establishing labor earlier, with a resultant reduction in the admission-to-delivery interval, compared with the use of a placebo pessary. The cesarean delivery rates in the two groups were similar, and there were no significant differences in neonatal outcome. A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks' gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient's own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks' gestation. Two hundred consecutive women with uncomplicated pregnancies, at or within 4 days of their expected date of confinement, were prospectively randomized into 2 groups. One group had expectant management, with twice weekly surveillance tests, while the other group had 3 mg of vaginal prostaglandin E2 as outpatient treatment. There were 104 women in the expectant group and 70 in the induction group (26 women allocated to induction preferred no treatment). The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group (p < 0.001). While meconium was much less frequent in the induction group (p < 0.002), all other outcome measures, including cesarean section rates, incidence of macrosomia, and Apgar scores, were similar in the two groups. A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended. To compare two prostaglandin (PG) E2 preparations for pre-induction cervical ripening in a randomized clinical trial.
                Two milligrams of vaginal PGE2 gel was compared with a vaginal PGE2 3-mg tablet in 200 nulliparous women. Outcomes assessed were induction failure, need for labor augmentation, pain relief requirements, fetal heart rate (FHR) abnormalities, operative delivery rate, induction-to-delivery interval, neonatal condition, and occurrence of uterine hyperstimulation.
                There was no statistical difference in pre- and post-dose cervical scores. Compared with the tablet group, women in the gel group were more likely to have significant FHR abnormalities in early labor (odds ratio [OR] 4.77, 95% confidence interval [CI] 1.15-19.5) requiring cesarean delivery. Fetal heart rate tracings in the active phase of labor were also more likely to be abnormal in the gel group (chi 2 = 4.31, P < .05). Compared with the gel group, women in the tablet group were significantly more likely to require operative delivery for poor progress in labor (OR 2.83, 95% CI 1.20-7.24). Other clinical outcomes were identical, with no significant differences in the overall rate of failed induction, cesarean delivery, rate of assisted delivery, requirement for oxytocin infusion, induction-to-delivery interval, pain relief requirements, or neonatal condition.
                When compared with the PGE2 tablet, the use of PGE2 gel for cervical ripening and labor induction in nulliparous women did not result in significant improvements in labor outcome. Whereas the gel was associated with an increase in significant FHR abnormalities, the tablet was associated with an increase in the rate of operative delivery for poor progress in labor. In 345 women with a favorable cervical score at due date, labor was either induced by means of intravaginal application of tablets containing 3 mg of prostaglandin E2 or spontaneous onset of labor was awaited until the 42nd week of pregnancy. Eighty percent of the nulliparae and 96.3% of the multiparae of the induction group gave birth within 24 h of the administration of the first tablet. All pertinent delivery intervals were significantly shorter in this group compared to those women where spontaneous onset of labor was awaited. The rate of operative deliveries was lower in the induction group. With the exception of 1 fetal death 3 days after due date, fetal outcome was excellent in both groups. Elective induction was at least equivalent to awaiting the onset of spontaneous labor and was not associated with higher complication rates due to the method of induction. The unfavorable cervix remains a major obstacle to the successful induction of labor. Reported are results from an ongoing study of topical prostaglandin preparations used to effect preinduction cervical ripening. The current study compares the efficacy of 40 mg of prostaglandin (PG) F2 alpha versus 5 mg of PGE2, applied to the cervix in a methyltylose gel the night before attempted induction of labor. A prospective double-blind protocol was used similar to that which previously established the efficacy of the 5 mg of PGE2 preparation versus placebo at this institution. Results indicate the superiority of the PGE2 preparation as measured by change in Bishop score, Pitocin requirement, rate of cervical dilatation, and percentage of failed inductions. Cesarean section rates were similar in the two study groups, and no fetal or maternal morbidity was attributable to the preinduction ripening technique. To shorten post-date pregnancies in a safe, effective manner by outpatient acceleration of cervical ripening.
                Eighty patients with uncomplicated pregnancies at or beyond 41 weeks' gestation and a cervical Bishop score less than 9 were randomized to daily self-administered, 2-mg intravaginal prostaglandin E2 (PGE2) or placebo suppositories. Each followed a standard post-date antepartum surveillance protocol. Patients were admitted for spontaneous labor or for induction if the Bishop score reached 9, antepartum testing was nonreassuring, exclusion criteria were fulfilled, or if the gestational age reached 44 weeks.
                Fewer suppositories were used in the PGE2 group (four versus seven; P = .006), resulting in earlier gestational age on admission (295 versus 297 days; P = .021) and lower antepartum testing charges ($476.97 versus $647.29; P = .001). Labor and delivery time was significantly decreased in nulliparas (10.7 +/- 5.1 versus 15.3 +/- 7.6 hours; P = .035).
                Daily low-dose, patient-administered PGE2 vaginal suppositories can decrease the gestational length and cost of uncomplicated post-date pregnancies by reducing the time to achieve a favorable cervix, the need for antepartum testing, and, potentially, post-date-related complications. A randomized blinded investigation was undertaken to determine the efficacy and safety of sequentially applied intravaginal prostaglandin E2 (PGE2) gel for accelerating cervical ripening in an outpatient setting in low-risk prolonged pregnancies. Fifty women with uncomplicated pregnancies at or beyond 41 weeks' gestation and Bishop scores below 9 received twice-weekly outpatient administration of gel containing 2.0 mg of PGE2 or placebo. Thirty nulliparas and 20 multiparas were enrolled. The PGE2 gel failed to improve cervical ripening over placebo, as judged by Bishop scores. There was no difference between the groups in gestational age on admission to the labor and delivery suite, number of gel applications, requirement for oxytocin, incidence of cesarean delivery, or neonatal outcome. Only two patients (4%) experienced regular uterine contractions after gel insertion; these subsided spontaneously in both. None of the subjects experienced labor, tetanic contractions, evidence of fetal distress, or any other side effects related to gel insertion. We conclude that PGE2 gel in this dosage may be used safely in an outpatient setting, but more frequent application or earlier initiation may be required to produce a clinical effect. As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another.
                We studied 5041 women with prelabor rupture of the membranes at term. The women were randomly assigned to induction of labor with intravenous oxytocin; induction of labor with vaginal prostaglandin E2 gel; or expectant management for up to four days, with labor induced with either intravenous oxytocin or vaginal prostaglandin E2 gel if complications developed. The primary outcome was neonatal infection. Secondary outcomes were the need for cesarean section and women's evaluations of their treatment.
                The rates of neonatal infection and cesarean section were not significantly different among the study groups. The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group, 3.0 percent for the induction-with-prostaglandin group, 2.8 percent for the expectant-management (oxytocin) group, and 2.7 percent for the expectant-management (prostaglandin) group. The rates of cesarean section ranged from 9.6 to 10.9 percent. Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management (oxytocin) group (4.0 percent vs. 8.6 percent, P<0.001), as was postpartum fever (1.9 percent vs. 3.6 percent, P=0.008). Women in the induction groups were less likely to say they liked "nothing" about their treatment than those in the expectant-management groups.
                In women with prelabor rupture of the membranes at term, induction of labor with oxytocin or prostaglandin E2 and expectant management result in similar rates of neonatal infection and cesarean section. Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management. Women view induction of labor more positively than expectant management. Prostaglandin (PG) E2 has proven effective in many studies as a pre-induction agent for cervical ripening. The purpose of this study was to compare the efficacy of a 5-mg dose of PGE2 prepared gel with that of a quartered PGE2 20-mg suppository. Previous studies have documented uniform distribution of PGE2 in the suppository. After 90 patients entered the study, there appeared to be an unacceptable rate of hyperstimulation following the induction dose using the suppository. The study was discontinued, and data analysis revealed a 24% hyperstimulation rate with the quartered suppository versus 0% with the gel. The successful vaginal delivery rates were equivalent, at 75% for the gel and 66% for the suppository. The 5-mg quartered suppository appeared to initiate an unacceptable amount of uterine activity, much greater than with the 5-mg gel dose. Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor.
                A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring.
                The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required.
                Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring. The purpose of the study was to determine the safety and efficacy of outpatient intravaginal prostaglandin E2 (PGE2) and membrane stripping in promoting labor in the uncomplicated postdate pregnancy. In a double-blind placebo-controlled study, 150 enrollees were randomized to one of four treatment groups; group I, no membrane stripping and placebo gel; group II, no membrane stripping and PGE2 gel; group III, membrane stripping and placebo gel; and group IV, membrane stripping and PGE2 gel. The treatments were administered at 287 days (41 weeks) and 294 days (42 weeks) of gestation, then every 3-4 days until 307 days (43 completed weeks) of gestation. The patients in group IV had the shortest interval to delivery with a median of 1 day, P = .001, and the fewest antenatal surveillance visits with only 21% requiring more than one visit, P = .02. Group I patients in comparison, had a 7-day median to delivery, and 61% required more than one visit. The time spent in labor and delivery and the need for oxytocin augmentation was not significantly reduced in groups II, III, and IV. No adverse side effects to either mother or neonate could be directly attributed to this outpatient treatment combination. We conclude that intravaginal PGE2 gel combined with membrane stripping reduces postterm pregnancies and antenatal visits in our patients. nan The purpose of this study was to determine if prostaglandin E2 in a controlled-release vaginal pessary can produce cervical ripening at term.
                This was a double-blind, randomized, placebo-controlled study conducted at a university center and involving 81 patients with 42 receiving active agent. Categoric data were analyzed by Pearson's chi 2 or logistic regression. Continuous variables were analyzed by analysis of variance and the F test.
                Prostaglandin E2 was significantly better than placebo at cervical ripening and at decreasing the time to rupture of membranes, the time to onset of labor, the need to give oxytocin, and the time to vaginal delivery. Multiparous women benefitted more than primiparous ones. The cesarean section rate decreased only for multiparous women. Uterine hyperstimulation occurred only with prostaglandin E2 and after the onset of labor.
                Prostaglandin E2, when administered in a controlled-release vaginal pessary, is affective in producing cervical ripening at term. This agent should be used on inpatients who are under continuous monitoring and it should be removed at the onset of labor. The outcome of labor induced by use of a glyceride-based vaginal suppository of prostaglandin E2 (PGE2) inserted 3 hours before amniotomy, when the cervix is favorable, has been assessed. Using 5 mg PGE2 for primigravidas and 2.5 mg for multigravidas, 63% of the former and 81% of the latter established labor and were delivered of their infants without oxytocin augmentation, allowing ambulation during early labor. No maternal complications were detected as a result of the PGE2 treatment. Compared with patients undergoing conventional induction by amniotomy and immediate oxytocin titration there was no difference in the duration of labor, with a few patients establishing labor and giving birth quickly with both induction methods. Fetal distress was less common following PGE2 treatment than following conventional induction, with three patients in each group requiring delivery by cesarean section. Cephalopelvis disproportion in the second stage of labor requiring cesarean section to deliver occurred more frequently in the prostaglandin-treated group, possibly as a result of reduced upper segment contractility in the first stage of labor with subsequent poor fetal head molding. Epidural analgesia and postpartum hemorrhge were both reduced following PGE2-induced labor. Prostaglandin E2 tablets administered vaginally succesfully induced labour in 64% of patients. There were no maternal or fetal complications. Comparison of the Bishop score failed to identify any factors which significantly influenced the success rate. The purpose of this study was to determine if prostaglandin E2 (PGE2) in a controlled-release vaginal insert with retrieval system can produce cervical ripening at term. This was a multicenter, double blind, randomized, placebo-controlled study involving 206 patients with 102 receiving active agent. A successful outcome was defined as a change in Bishop score of > or = 3, or a Bishop score of > or = 6 at 12 h or delivery within 12 h of the insert placement. Analysis was by Fisher's exact test, Wilcoxon's two-sample rank-sum test, and Student's t-test where appropriate. One hundred ninety-three women completed the protocol. Initial Bishop scores were 2.6 +/- 1.2 and 2.5 +/- 1.4 in the PGE2 and placebo groups, respectively. The incidence of cesarean delivery was identical in the two groups. Uterine hyperstimulation lasted 2-13 min in 5 PGE2 patients (4.9%) with 1 patient requiring tocolysis. More patients in the PGE2 group had a change in Bishop score of > or = 3 (62% vs. 40%; P = 0.002), a Bishop score > or = 6 after 12 h (46% vs. 34%; P = 0.11), and vaginal delivery within 12 h (6.5% vs. 1%; P = 0.055). Sixty-five percent of PGE2 group patients had a successful outcome vs. 44% of control patients (P = 0.001). In conclusion, when administered in a controlled-release vaginal insert with a retrieval system, PGE2 is effective in promoting cervical ripening at term. The intravaginal application of prostaglandin E2 for preinduction cervical ripening has proved to be advantageous in the management of patients with an unfavorable cervix. The purpose of this double-blind randomized investigation was to compare the efficacy and safety of two methods of prostaglandin E2 delivery. Patients who were to have preinduction cervical ripening because of an unfavorable cervix (Bishop score less than or equal to 4) were randomly assigned to be given a single dose of prostaglandin E2 as either 2.5 mg of gel or a 3.0 mg "chip" intravaginally in a placebo-controlled manner. Sixty-nine patients received the active prostaglandin E2, 34 in the gel group and 35 in the "chip" group. The groups were similar in maternal age, race, parity, gestational age, and initial Bishop score. Both forms of prostaglandin E2 were easy to administer and helpful in priming an unfavorable cervix. The need for, duration of, and maximum dose of oxytocin were similar in both groups. Cesarean delivery because of failed induction occurred in 5 of 35 (14.3%) patients receiving a "chip" and 4 of 34 (11.8%) receiving the gel. However, patients receiving a "chip" experienced a 20% (7/35) incidence of hyperstimulation, compared with 2.9% (1/36) in those receiving the gel (p less than 0.05). The only case requiring immediate cesarean delivery because of intractable uterine hyperstimulation received a "chip." We conclude that both methods were effective for cervical ripening, but the lower incidence of uterine hyperstimulation seen with the gel would suggest that it is preferable to the "chip." A study was conducted to compare the efficacy and safety of two methods of delivering prostaglandin E2 (PGE2) as a low-dose gel delivered in up to two sequential, 2.5-mg doses and as a single-dose, controlled-release, 10-mg pessary. A cervical change was present in both groups, but a Bishop score > or = 8 occurred in more nulliparous patients in the pessary than in the gel group by 12 hours after dosing. Labor was initiated without oxytocin more frequently in the pessary than gel group for nulliparas and multiparas. Reversal of uterine hyperstimulation was possible by removal of the pessary without tocolytic therapy. The controlled-release PGE2 pessary was more effective in changing the cervix in nulliparas and in initiating labor and offered the advantage of removal when desired. In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy. 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. The purpose of the trial was to determine whether a sustained release preparation of prostaglandin E2 (Propess) is better in inducing labour when compared with the more widely used short-acting (instant-release) preparation (Prostin). A randomised controlled clinical trial involving 100 pregnant women at term with an indication for induction of labour was conducted in a district general hospital in the UK over a 1-year period. Women were randomised to receive one of the two preparations. The study revealed that there was no statistically significant difference in time to onset of labour, duration of labour, total time from induction to delivery, method of delivery, and analgesia requirements. The number of preparations required to induce labour were significantly less in the Propess group. Our data suggest that both Propess and Prostin are safe and effective in induction of labour, for either primips or multips. However, Prostin use is more cost-effective. Plasma levels of bicyclic PGE2 (PGE2M) were measured after administration of a 5mg, PGE2 slow release hydrogel pessary and a 3mg vaginal tablet (Upjohn). Twenty-four women of low parity with favourable induction features were randomised to receive either the hydrogel pessary or the vaginal tablet. A single pessary was administered and amniotomy was performed after 4 hours. Augmentation with oxytocin was carried out after amniotomy if required. Both groups showed a rise in plasma PGE2 levels in keeping with the release profiles of the pessaries. Wide interindividual differences in absorption were found. In a randomized study, uterine activity patterns were characterized with a portable pressure-sensitive device in 40 nonlaboring women at term with an unfavorable cervix who were undergoing preinduction cervical ripening with prostaglandin E2. The prostaglandin E2 was inserted into the posterior vaginal fornix as a single dose of either a 2.5 mg methylcellulose gel (20 cases) or 10 mg controlled-release pessary (20 cases). Uterine activity monitoring began 1 hour before dosing and continued for 12 hours. For those treated with the gel, low-amplitude, high-frequency contractions began within the first hour, reached a peak within 4 hours, and initiated sustained high-amplitude contractions in 10 (50%) cases. With the controlled-release pessary, low-amplitude, high-frequency contractions had a slightly later onset, reached a peak between the fifth and eighth hours, and initiated sustained high-amplitude contractions in 18 (80%) cases. Uterine hyperstimulation occurred in two (10%) pessary cases, with no adverse effect after removal. We conclude that low-amplitude, high-frequency uterine contractions began with either method of intravaginal prostaglandin E2 delivery but led to sustained, high-amplitude contractions primarily with the pessary. Induction of labour is a common obstetric intervention. When the cervix is unfavourable ripening agents are used, commonly prostaglandin E2. There are several methods of administration of prostaglandin E2 and little comparative work has been performed as to their acceptability by patients. Patients undergoing induction of labour by prostaglandin E2 were randomised to receive either intravaginal gel or an intravaginal slow-release pessary. Patient satisfaction with the method received was then assessed. Sixty-nine patients were randomised, 34 to receive gel and 35 to receive a pessary. Median scores for satisfaction of the induction process were the same for both methods; however, satisfaction with the labour was increased with those who had been randomised to the pessary group (median pessary=5, gel=4). There may be a marginal improvement in patient satisfaction when a slow-release intravaginal prostaglandin E2 pessary is used for the induction of labour. Prostaglandin E2 is effective for induction of labor but many preparations exist using a variety of vehicles from which the active ingredient may not be equally available. Plasma concentrations of bicyclic PGE2 metabolite (PGEM) and 13, 14-dihydro, 15-keto PGF2 alpha (PGFM) were measured following administration of a 3mg PGE2 vaginal tablet or 1mg PGE2 vaginal gel to twenty-four parous women with favorable induction features, randomly allocated to receive one or other preparation. PGEM increased rapidly following both administration of the 3mg PGE2 vaginal tablet and the 1mg PGE2 vaginal gel, reaching a peak within 40 minutes of PGE2 administration. The maximal rise in PGEM in the gel group correlated directly with the change in cervical score and inversely with the need for augmentation with oxytocin and the induction-delivery interval. A secondary rise in PGFM was noted in both groups 3-4 hours following PGE2 administration. The magnitude of the increase in PGE2 may be important in the clinical response to PGE2 administration, while PGE2 absorption may switch-on endogenous PGF2 alpha production, similar to what is seen in spontaneous labor. Fifty-four patients were randomized in a double blind fashion into either a placebo group or a group treated with a 3 mg dose of an intravaginal prostaglandin E2 gel. The group receiving the prostaglandin E2 gel had a mean change in cervical score of 2.7 while the patients in the placebo group had no significant change. Even though a significantly higher number of patients in the prostaglandin group went into spontaneous labor, the incidence of cesarean section was not different between the two groups. Upon comparing the conflicting reports of various studies on the subject, it is concluded that the method of product preparation, particularly the source of prostaglandin E2 utilized and the choice of drug vehicle, may be important variables in determining treatment success, as measured in terms of decreased cesarean section rate. 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. Slow release prostaglandin pessary (propess) is compared with instant release prostaglandin gel (prostin) for the induction of labour in nulliparous women with a modified Bishop's score of less than 6. In this randomised study 50 women received prostin gel and 45 received propess. More than one dose of prostaglandin was required to achieve amniotomy more often in the propess group (53%) compared with the prostin group (34%) (P=0.03). Propess was unable to demonstrate any advantage over Prostin gel group. Propess was not cost-effective in this study. This study represents the first of its kind in Kuwait. Two preparations of prostaglandin E2 (PGE2) have been compared as agents for induction of labor. In a randomized controlled study of 200 women of low parity and unfavorable cervical induction features induction of labor by means of a single vaginal tablets of PGE2 was compared with locally prepared PGE2 vaginal pessaries. The gradual increase of uterine contractions and the establishment of labor in a similar way to that observed during spontaneous labor was more apparent after PGE2 tablets. Labor induction was successful in 80% of patients in PGE2 tablet group compared with 59% in PGE2 pessaries group. The incidence of cesarean section was equal in both groups (4%), but none was performed due to uterine hyperactivity. The data presented indicate that the PGE2 vaginal tablet is safe and effective in induction of labor in healthy women at term. A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term. To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term.
                A prospective randomized study.
                Labour Ward, Aberdeen Maternity Hospital.
                230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment.
                In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses.
                PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity.
                There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section.
                The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM. Fifty nine women with prelabour rupture of membranes, unfavourable cervix and no evidence of infection or fetal distress were randomized formally to receive prostaglandin E2 (3mg) gel or sterile K-Y Jelly intravaginally. Conservative expectant management was followed for the next 24 hours. The subsequent management of the labour followed departmental protocol. The women who received prostaglandin went into labour sooner and were delivered earlier but the duration of labour was not significantly different. There were no significant differences in other clinical outcomes. There was 1 case of uterine rupture in the prostaglandin group. We conclude that early intervention with prostaglandin E2 gel intravaginally confers no advantage compared with conservative management except for earlier confinement in this group of patients. To compare the efficacy and safety of a prostaglandin E2 (PGE2) vaginal insert with PGE2 administered as a vaginal tablet.
                A randomized, observational study was performed. Women requiring induction of labor were randomly assigned to receive either a 10-mg PGE2 vaginal insert (group 1, n = 100) or 3-mg PGE2 tablets twice at six-hour intervals (group 2, n = 100). The primary efficacy outcome variable was vaginal delivery within 24 hours of insertion. The criteria for safety were the occurrence of uterine hyperstimulation, abnormal fetal heart rate patterns, use of beta 2-sympathomimetic drugs and fetal outcome.
                No differences in terms of vaginal delivery or cesarean section within 24 hours of induction were found. The cesarean section rate was 21% in group 1 and 22% in group 2. The interval from insertion of the induction agent to the onset of regular uterine contractions and the insertion-to-delivery interval were not different between the two cohorts. No difference in the frequency of uterine hyperstimulation, use of beta 2-sympathomimetic drugs, abnormal fetal heart rate patterns, fetal outcome, or oxytocin and analgesic requirements were found. In seven of eight patients in group 1 who experienced uterine hyperstimulation, removal of the insert was sufficient to stop it, whereas in group 2, of nine cases, eight needed medical interventions to end hyperstimulation (P = .003).
                The continuous release of PGE2 from the vaginal insert permits controlled induction of labor, and easy removal of the drug in cases of uterine hyperstimulation is possible. Tylose gel containing either 1.5 mg, 3.0 mg or 10.0 mg of prostaglandin F2 alpha was inserted into the posterior vaginal fornix of 165 patients on the evening before induction of labour. A control group of 100 patients received the gel alone. There was a significant reduction in the induction-delivery interval in nulliparae receiving at least 3.0 mg of prostaglandin, whereas, in multiparae all doses achieved this effect. There was also a significant reduction in the incidence of forceps delivery in nulliparae who received 3.0 mg or more of the prostaglandin gel; however, there was no difference in the incidence of spontneous labour, epidural anaesthesia or Caesarean section between the patients who received prostaglandin or those receiving gel alone. A randomised controlled trial was conducted to compare the clinical efficacy and cost-effectiveness of Dinoprostone Slow Release Pessary (Propess) with Gel (Prostin) for induction of labour (IOL) at term. A total of 120 women requiring IOL at term with no previous uterine surgery and no contraindication to prostaglandins were included. The main outcome measures were efficacy of drug preparations, patient satisfaction and the cost-effectiveness. The secondary outcome measures noted were maternal complications during the labour, type of delivery, the neonate's Apgar scores at birth and 5 min and incidence of significant morbidities. There were insignificant differences between the two groups in induction-to-delivery interval, mode of delivery, number of women delivering within 24 h and neonatal outcomes. However, the number of vaginal examinations was significantly lower in the Propess group. Propess was found to be more cost effective compared with Prostin in view of single dose and less midwifery hours. The efficacy of a vaginal gel containing either 5 mg prostaglandin E2 (PGE2) or 25 mg prostaglandin F2 alpha (PGF2 alpha) to ripen the unfavourable cervix for labour induction was assessed in a double blind trial. PGF2 alpha, compared with PGE2, had little effect upon the clinical state of the cervix, but the resultant duration of labour in each of the two groups was shorter than in a control group. While the numbers of patients requiring oxytocin stimulation of labour and regional analgesia were reduced in both groups compared with the controls, PGF2 alpha was much less effective than PGE2. Uterine hypertonus was observed using both prostaglandins during an experimental study and the implications are discussed. Our objective was to determine the best treatment for parturients at term with an unfavorable cervix and premature rupture of membranes (PROM).
                In this prospective study, 96 women with PROM and an unfavorable cervix were randomized into one of three treatment groups: oxytocin induction, vaginal prostaglandin E2 gel followed by oxytocin, or expectant management.
                Length of labor, cesarean section rate, and maternal/neonatal morbidity were not significantly different. In contrast, the interval from PROM until delivery and length of hospital stay were significantly longer in the expectantly managed group than in the other groups. Four of the patients who received expectant management required delivery because of nonreassuring fetal assessments.
                Expectant management of PROM at term significantly prolongs hospital stay without decreasing the incidence of abdominal delivery or infectious morbidity. There appears to be potential for cord compression in patients managed expectantly without continuous electronic fetal surveillance. Eighty patients with a Bishop score of less than or equal to 4 were randomly administered vaginal triacetin gel containing placebo or prostaglandin E2 in 1, 2, and 3 mg doses. Twelve to sixteen hours later, those not in labor underwent oxytocin induction. Increasing doses of prostaglandin were effective in ripening the cervix, and the higher doses were associated with significant success in inducing labor. Although there are many comparative studies concerning the local administration of prostaglandin E2 gel for cervical ripening and labor induction, the safety, efficacy and the appropriate route and dose of the gel are still debated.
                One hundred and ten women with high-risk pregnancy and unripe cervix received prostaglandin E2 gel 1 mg intravaginally (n=35), 2 mg intravaginally (n=36) and 0.5 mg intracervically (n=39), maximally three times at 6-hour intervals for cervical ripening prior to labor induction. The safety, efficacy and optimal dose were assessed.
                The 2 mg intravaginal gel and the 0.5 mg intracervical gel were equally effective and more effective than the 1 mg intravaginal gel in labor characteristics such as ripening time and cesarean section rate, but not in labor time. However, the failure rate (labor could not be induced) was highest in the intracervical group (10.3%) compared to the intravaginal groups (2.9% and 2.8%), although the differences were not statistically significant. In the two intravaginal groups three and five patients received the third gel application and one patient in both groups could not be induced. In the intracervical group the ripening of the cervix failed in all patients, who received the third gel. The neonatal outcome was uneventful in all groups. There were two cases of uterine hypertonus associated with fetal bradycardia, one in the intracervical and one in the 2 mg intravaginal group. Thus careful fetal monitoring is necessary. Furthermore, the vaginal route has the advantage of an easier technique of administration and obviously lower risk for inadvertent extraamnial instillation.
                We recommend the use of multiple applications of 2 mg intravaginal prostaglandin E2 gel as a safe, effective and easy method for preinduction cervical ripening in high-risk pregnancies. More than three gel applications hardly increase the efficacy.
PGE2 increases successful vaginal delivery rates in 24 hours and cervical favourability with no increase in operative delivery rates. Sustained release vaginal PGE2 is superior to vaginal PGE2 gel with respect to some outcomes studied.
Further research is needed to assess the best vehicle for delivering vaginal prostaglandins and this should, where possible, include some examination of the cost-analysis.
[Note: The 10 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]