Induction of labor with prostaglandin E2 vaginal suppositories

A prospective randomized study of 85 parturients was undertaken comparing the safety and efficacy of a 3-mg prostaglandin E2 vaginal suppository with intravenous oxytocin for the induction of labor. All patients were required to have a Bishop's score of 5 or higher. Labor was successfully induced in 98% of the patients in both groups by their respective methods. Sixty-four percent of the patients receiving a 3-mg prostaglandin E2 suppository required no intravenous oxytocin. More specifically, 82% (23/28) of the parous patients but only 29% (5/17) of the nulliparous patients who received a single 3-mg prostaglandin E2 suppository for labor induction did not require oxytocin augmentation (P less than .005). The first and second stages of labor were not significantly different for the two groups, and there was no significant difference in the incidence of cesarean section. A 3-mg prostaglandin E2 vaginal suppository may be a useful alternative to oxytocin for the induction of labor in carefully selected patients.     

The sequential use of estradiol and prostaglandin E2 topical gels for cervical ripening in high-risk term pregnancies requiring induction of labor

We compared the safety and efficiency of 200 mg of estradiol valerate prepared as a topical cervical gel as a preripening agent when used 6 hours before the application of 2 mg of prostaglandin E2 gel for the purpose of cervical ripening in 40 high-risk obstetric patients before indicated oxytocin induction of labor. When compared with a placebo prostaglandin E2 dosage, the estradiol had no effect on the change of Bishop score, length of labor, amount of oxytocin required, or the cesarean delivery rate. While no uterine contractions were noted after the application of the estradiol, 85% of patients had recordable uterine activity after the application of prostaglandin E2, suggesting that even at the 2 mg dosage this sequential regimen is not appropriate for local cervical ripening.     

Does prostaglandin confer significant advantage over oxytocin infusion for nulliparas with pre-labor rupture of membranes at term?

Ninety-four nulliparous women with a poor cervical score (less than 6) who had premature rupture of membranes at term were randomized by sealed envelope into two groups. One group received immediate stimulation of labor with oxytocin infusion. The second group received two prostaglandin E2 (PGE2) 3-mg pessaries 4 hours apart, followed by oxytocin infusion, if necessary. The interval between initiation of therapy to onset of labor was significantly longer in the PG group, but the length of labor was similar in both groups. The maximum dose of oxytocin needed was significantly higher in the oxytocin group. The cesarean delivery rate in the oxytocin group was 14.9%, compared with 19.1% in the PG group (not significantly different). All seven cesareans in the oxytocin group and seven of nine in the PG group were for failed stimulation of labor. Neonatal Apgar scores at 1 and 5 minutes and admission to the neonatal intensive care unit were similar in the two groups. The incidence of maternal and neonatal infection was small and was not different in the two groups. The use of PGE2 3-mg pessaries 4 hours apart, followed by oxytocin infusion if necessary, did not confer any benefit over the use of intravenous oxytocin in obstetric or neonatal outcome when both agents were started a few hours after admission.     

Prostaglandin E2 in tylose gel for cervical ripening before induction of labor

Two hundred seventeen women who received 3 mg of prostaglandin E2 (PGE2) gel applied to the cervix followed by adjunctive oxytocin were compared to 94 patients whose labor was induced with oxytocin alone (OA). Postdatism, pregnancy-induced hypertension and rupture of the membranes were the major indications for induction of labor, accounting for 70% of the PGE2 group and 88% of the OA group. Mean initial cervical scores were found to be significantly less favorable among PGE2 patients as compared with OA patients. Though PGE2 was associated with a significant improvement in mean cervical scores, responsiveness of the cervix to PGE2, as determined by clinical examination, was not necessary for a successful induction. Failed inductions were infrequent in both groups. Nulliparous PGE2 patients with unfavorable cervical scores had fewer cesarean sections (CSs) and shorter labors than did their OA counterparts. Complications were uncommon but largely due to the subsequent use of oxytocin. Patients with prior CSs were safely induced following PGE2 cervical ripening.     

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.     

Oral misoprostol vs. intravaginal prostaglandin E2 for preinduction cervical ripening. A randomized trial

OBJECTIVE: To compare orally administered misoprostol with intravaginal prostaglandin E2 for cervical ripening and labor induction. STUDY DESIGN: Patients presenting with medical or obstetric indications for labor induction whose Bishop's score was < or = 6 were randomly allocated to receive either 50 micrograms of oral misoprostol or 4 mg of intravaginal prostaglandin E2. If adequate cervical ripening (Bishop score of 9 or cervical dilatation of 3) or active labor did not ensue, repeat doses of each medication were administered every four hours. A maximum of six doses of either oral misoprostol or intravaginal prostaglandin E2 was permitted. Intravenous oxytocin was subsequently administered according to a standardized infusion protocol. RESULTS: Sixty patients were enrolled, with 29 randomized to the oral misoprostol arm and 31 to the prostaglandin E2 group. The data on 58 patients were eligible for analysis. Delivery occurred within 48 hours in 96.4% (27/28) of those administered oral misoprostol as compared to 76.7% (23/30) of those who received intravaginal prostaglandin E2 (P = .03). The mean time intervals from the start of induction to delivery were similar between the two groups (1,496 +/- 120 vs. 1,723 +/- 230 minutes, P = .40). No statistically significant differences existed between the two groups with respect to intrapartum complications, tachysystole, uterine hyperstimulation or adverse neonatal outcomes. CONCLUSION: Oral administration of misoprostol is an effective alternative to intravaginal prostaglandin E2 for preinduction cervical ripening.     

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.     

Induction of labor using high-dose or low-dose prostaglandin vaginal pessaries

Two hundred women were studied in a randomized controlled trial of induction of labor using high-dose (3 mg) or low-dose (0.5 mg) prostaglandin E2 vaginal pessaries. Induction using 3-mg pessaries was more successful, with a shorter overall induction-delivery interval and less requirement for analgesia, although uterine hyperstimulation occurred in two patients. In contrast, the low-dose regimen did not cause hypertonus and, though less successful in inducing labor, the total dose of prostaglandin E2 used was considerably less than in the 3-mg group. The cesarean section rate when the cervix was initially unfavorable was high in both groups (high dose 18.2%, low dose 16.7%). The response to prostaglandin E2 did not relate closely to the initial cervical state.     

Comparison of prostaglandin E2 and intravenous oxytocin for induction of labor

One hundred nulliparas at term were randomly given oxytocin intravenously or prostaglandin E2 (PGE2) gel (0.5 mg PGE2) intracervically in order to study the effect on cervical ripening and the frequency of successful inductions. In the presence of a favorable cervix both methods seemed equally efficacious in inducing labor. However, when the cervix was unfavorable, 53% of the patients could be delivered with PGE2 gel, compared with 31% when oxytocin was given. In patients with a highly unfavorable cervix this difference was significant (P less than 0.02). In patients not induced into labor, PGE2 gel caused a considerable ripening of the cervix, with a change in Bishop score from 2.9 to 6.3. In patients undelivered after oxytocin stimulation, no change in Bishop score occurred. This effect of locally applied PGE2 gel on cervical ripening was highly significant (P less than 0.001). No adverse maternal or perinatal effects were observed, irrespective of the mode of treatment.     

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 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.     

Prostaglandin E2 gel for cervical ripening and induction of labor: a critical analysis

This report summarizes the cumulative experience of 3313 pregnancies represented in 59 prospective clinical trials in which intracervical or intravaginal prostaglandin E2 gel was used for cervical ripening before induction of labor. Results indicate that local prostaglandin E2 is superior to placebo or no therapy in enhancing cervical effacement and dilation, reducing initial induction failures, shortening the induction-delivery interval, reducing oxytocin use, and lowering the rate of cesarean section because of failure to progress. Certain advantages also exist for labor induction in the presence of a favorable cervical state. Uterine hyperstimulation or pathologic fetal heart rate patterns before oxytocin administration occur in less than 1% of reported cases and are usually dose related, self contained, and reversible with the use of beta-adrenergic tocolytic therapy. Maternal systemic effects in these low doses are negligible. Worldwide clinical experience has clearly demonstrated that prostaglandin E2 gel administered before induction of labor is of major therapeutic benefit and should become commercially available for more than investigational use.     

Balloon cervical ripening with extra-amniotic infusion of saline or prostaglandin E2: a double-blind, randomized controlled study

OBJECTIVE: To compare extra-amniotic infusion of diluted prostaglandin (PG) E2 solution with saline infusion in balloon cervical ripening and labor induction. METHODS: Women with pregnancy complications and Bishop scores of 3 or lower (n = 116) were assigned randomly to receive extra-amniotic infusion (1 mL/minute) of normal saline or PGE2 in saline (0.5 microg/mL) through a Foley catheter with a 30-mL inflated balloon. We induced labor using intravenous oxytocin only when labor had not developed by 6 hours after balloon expulsion. Analysis was by intent-to-treat. We assessed ripening efficiency and course of labor in women who had spontaneous balloon expulsion (n = 110) and trial of labor (n = 107), respectively. RESULTS: Ripening with PGE2 was associated with significantly shorter mean (+/- standard error of the mean [SEM]) time for balloon expulsion (4.7 +/- 0.4 versus 6.5 +/- 0.6 hours) and with significantly higher Bishop scores (P <.002), compared with ripening with saline. In the PGE2 group, rates of labor induction (15%) and oxytocin use (37%) were significantly lower than in the saline group (51% and 72%, respectively). The groups did not differ significantly in other labor abnormalities, labor duration, mode of delivery, birth weight, Apgar scores, and puerperal morbidity. CONCLUSION: Cervical ripening by extra-amniotic balloon and PGE2 infusion is faster and more effective than by balloon and saline infusion, resulting in a higher rate of spontaneous labor and a lower rate of oxytocin use.     

Double-blind comparison of intravaginal prostaglandin E2 gel and "chip" for preinduction cervical ripening

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."     

Two different regimens of preinduction ripening of the uterine cervix with prostaglandin E2: a randomized clinical study

A randomized clinical study was designed to test the relative efficacy of preinduction cervical ripening with 0.25 mg prostaglandin E₂ (PGE₂), repeated if necessary (group 1) compared to a single maturation with 0.50 mg PGE₂ (group 2). In group 1 (n = 42), the ripening process was repeated every day until spontaneous onset of labor occurred or induction with oxytocin was decided (for improved Bishop score above 5, or maternal or fetal distress). In group 2 (n = 42) the patients who had not labored 12 h after the maturation procedure had labor induced with oxytocin, irrespective of their cervical status. In group 1, 28 patients experienced repeated maturations (from 2 to 9). Thirty patients had an induction of labor with oxytocin in group 2 and only 12 in group 1 (P < 0.0001). There were four failures of induction of labor in group 2 and none in group 1 (P < 0.05). Three episodes of myometrial hyperstimulation requiring an emergency cesarean section for acute fetal distress occurred in group 2 and none in group 1. There were 13 cesarean sections in group 2 and eight in group 1. The outcome of pregnancy was otherwise similar in both groups. In order to avoid failure of induction of labor, pre-induction cervical ripening with 0.25 mg PGE₂, repeated daily if necessary, is therefore recommended in high risk pregnancy unless a severe maternal or a fetal distress call for a prompt delivery irrespective of the cervical status.     

A randomized trial of prostaglandin E2 in a controlled-release vaginal pessary for cervical ripening at term.

OBJECTIVE: The purpose of this study was to determine if prostaglandin E2 in a controlled-release vaginal pessary can produce cervical ripening at term. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Preinduction cervical ripening with prostaglandin E2 (Prepidil) gel

The effect of preinduction cervical ripening with Prepidil, a commercially prepared prostaglandin E2 gel (0.5 mg), on the outcome of induction of labor with intravenous oxytocin was investigated. Fifty-nine pregnant women were randomized either to receive intracervical application of the gel or to undergo sham application. Compared to control subjects, patients in the group given Prepidil had significant increases in cervical Bishop scores, shorter induction-to-delivery intervals, lower maximum doses of oxytocin, and fewer days of induction. Systemic side effects were minimal, but 37% (11 of 30) of the gel-treated patients experienced labor prior to receiving oxytocin and 20% (six of 30) were actually delivered during the 12-hour ripening period. No differences in route of delivery or fetal outcome were found between the two groups.     

Cervical ripening and labor induction with prostaglandin E2 gel: a placebo-controlled study

A randomized double-blind, placebo-controlled study was undertaken to evaluate the effect of a single intracervical application of prostaglandin E2 gel on the ripening of the cervix and on the subsequent induction of labor with oxytocin in patients with low Bishop scores (less than or equal to 4). Compared to controls receiving gel only, the group receiving prostaglandin E2 gel had significant increases in their cervical Bishop scores, shorter induction-to-delivery intervals, shorter time requiring use of oxytocin, and more successful labor induction without oxytocin. Systemic side effects were minimal and fetal outcomes were comparable, as were the routes of delivery.     

A scoring system for induction of labor using prostaglandin E2 vaginal tablets

A randomized controlled trial was carried out in order to establish the efficacy of a scoring system for calculating the dose of vaginal prostaglandin E2 tablets for the induction of labor. One hundred ten women were included in the study. The patients received a dose of prostaglandin E2 calculated according to a scoring system based on the Bishop's score, or the standard dose of 3 mg repeated 6 h later if labor did not start. The percentage of inductions achieved was the same with both regimens (92.7%). The mean total dose used in the scoring system-group (2.7 mg) was significantly lower than that used in the 3-mg group (3.5 mg, P less than 0.025). Thirty-seven of 55 women receiving the scoring dose delivered with amounts of 2.5 mg prostaglandin E2 or less. Three cases of uterine hyperstimulation were observed in the 3-mg group whereas no cases were observed in the scoring group. The scoring system is proposed as a method for calculating the dose of vaginal prostaglandin E2 for induction of labor and minimizing the risk of overdosage.     

Intracervical misoprostol and prostaglandin E2 for labor induction.

OBJECTIVES: To compare the safety and efficacy of misoprostol with PGE(2) for induction of labor by intracervical administration. METHODS: Eighty-six women with indications for labor induction at term were randomly assigned to two groups. Each woman received either 50 microg of misoprostol or 0.5 mg of prostaglandin E(2) intracervically. If labor was not initiated after 4 h, the same dose was repeated every 4 h to a maximum of 200 microg of misoprostol or 1.5 mg of PGE(2) until adequate labor was achieved. RESULTS: Forty-three women were allocated to the misoprostol group and 43 to the prostaglandin E(2) group. Misoprostol was more effective than PGE(2) in producing cervical changes (P<0.025). Delivery within 12 h after the first administration occurred more often in the misoprostol group than in the PGE(2) one (85% vs. 56%, P<0.05). Less patients in the misoprostol group required oxytocin augmentation than in the PGE(2) one (16.3% vs. 39.5%, P<0.05). Uterine tachysystole and hyperstimulation occurred more frequently in the misoprostol group (44.1%) than in the PGE(2) group (18.7%) (P<0.05). Nevertheless, no statistically significant differences were noted between the two groups including mode of delivery and neonatal or maternal adverse outcome. The interval from induction to vaginal delivery was significantly shorter in the misoprostol group (480+/-172 min vs. 657+/-436 min, P<0.01). CONCLUSIONS: Compared with prostaglandin E(2), intracervical misoprostol is more effective in cervical ripening and labor induction at term. The higher frequency of uterine hypercontractility associated with the use of misoprostol did not increase the risk of adverse intrapartum and neonatal outcomes.