Sequential outpatient application of intravaginal prostaglandin E2 gel in the management of postdates pregnancies

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.     

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.     

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.     

Pre-induction cervical ripening with prostaglandin E2 gel: intracervical versus intravaginal route

The aim of our study was to evaluate the best method for cervical ripening before a classical induction with amniotomy and oxytocin. One hundred term pregnant patients who presented an unfavorable cervix and an indication for the induction of labor were assigned randomly to either 0.5 mg prostaglandin (PG) E2 gel intracervically (N = 52) or 3 mg PGE2 gel intravaginally (N = 48). The intravaginal gel had a greater effect on cervical ripening according to a modification of the Bishop score than did intracervical gel, but it had a higher incidence of side effects.     

Comparison of intravenous oxytocin and vaginal prostaglandin E2 gel in women with unripe cervixes and premature rupture of the membranes

To induce cervical priming and labor, 20 nulliparous term pregnant women with premature rupture of the membranes and unfavorable cervical states were randomly given either oxytocin intravenously or 4 mg prostaglandin E2 in gel intravaginally. One of ten women receiving oxytocin had a favorable cervical state within five hours and vaginal delivery within 24 hours after the start of the infusion compared with six of ten women after prostaglandin E2 gel application. This difference is statistically significant (P less than .01). The number of instrumental deliveries was nine (four cesarean sections and five vacuum extractions) in the oxytocin-treated patients compared with only two vacuum extractions in women who received prostaglandin E2 gel. This difference is also statistically significant (P less than .01, Fischer exact test). In a subsequent open study, 4 mg prostaglandin E2 gel was applied vaginally to 17 term pregnant women of mixed parity with premature rupture of the membranes and unfavorable cervixes. In 12 women a favorable cervical state was achieved within five hours after gel application, and all these women were delivered within 24 hours. None of the women required cesarean section but two required delivery by vacuum extraction. There were no perinatal losses, but two infants in the oxytocin-treated group had Apgar scores less than 7 at five minutes. At pediatric follow-up after two and six months, all infants were normal. In both obstetric and perinatal outcome prostaglandin E2 gel thus seems to be superior to oxytocin for labor induction in term pregnant patients with premature rupture of the membranes and unfavorable cervixes.     

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.     

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.     

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."     

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.     

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.     

Cervical ripening before medical induction of labor: a comparison of prostaglandin E, estradiol, and oxytocin

Objective: Our purpose was to evaluate the effectiveness of oxytocin, prostaglandin, E² intracervical gel, and estradiol cream for ripening the very unfavorable cervix in patients requiring induction of labor at term.Study design: This prospective, randomized study was conducted in a population of women with a very unfavorable cervix (Bishop score <4) requiring induction of labor. The patients received prostaglandin E² gel (0.5 mg) intravervically (three doses 6 hours apart), 4 mg estradiol cream in the anterior fornix of the vagina (three doses 6 hours apart), or oxytocin at induction per protocol with an infusion pump.Results: Ninety-nine women were recruited into this trial and evenly distributed among the three groups. The demongraphics of maternal age, race, parity, gestational age, initial Bishop score, and indication for induction were similar among the groups. The incidence of cesarean deliveries was similar in the three groups with approximately 59% of pregnancies delivered abdominally. For patients undergoing abdominal delivery the maximum cervical dilatation among the oxytocin, estradiol, and prostaglandin E² groups was similar (3.90 = 3.02 cm, 3.63 ± 2.79 cm, and 4.65 ± 2.78 cm, respectively; p > 0.05). For all patients birth weight and Apgar scores at 1 and 5 minutes were comparable across all regimens (p > 0.05). In the subset of patients delivered vaginally patients receiving oxytocin for cervical ripening had the greatest improvement on Bishop score over baseline (p = 0.023) with an improvement of 7.08 ± 2.42.Conclusion: No differences were detected among prostaglandin E₂ gel, estrogen, and oxytocin in relation to cervical ripening in patients with an unfavorable cervix at term who require an induction of labor. Patients with a very unfavorable cervix at term who require delivery may benefit from serial ripening and inductions.     

Cervical priming and/or induction by intracervical application of PGE2-gel in term patients with preeclampsia and unfavorable cervical states

92 preeclamptic women with unfavorable cervical states were treated with intracervical application of prostaglandin E2 (PGE2) in gel for cervical priming and/or labor induction. 55 (60%) were delivered after a single PGE2-gel application. In 27 (29%) the cervical state was improved after 24 h and labor could be induced by oxytocin infusion. Thus, 89% of the women were delivered within 48 h after a single PGE2-gel application. In 10 women (11%) a second PGE2-gel application had to be done before oxytocin infusion. The frequency of cesarean sections was low (5%). No case of uterine hypertonus was seen. No gastrointestinal side effects were observed. All newborn infants had an apgar score at 5 min of more than 7 and were in good condition.     

Cervical ripening and labor outcome with preinduction intracervical prostaglandin E2 (Prepidil) gel

Delivery with an unfavorable cervix using oxytocin is frequently unsuccessful. Used widely in Europe and increasingly in this country, locally applied prostaglandin E2 appears to improve labor induction. The present study prospectively evaluated the efficacy and safety of a prostaglandin gel (0.5 mg) placed intracervically. The use of the gel, when compared to a control group who received no pretreatment prior to labor induction, resulted in improved Bishop scores (7.5 +/- 1.0 vs. 1.8 +/- 0.3, P less than 0.0001), reduced induction to delivery intervals (10.1 +/- 2.1 vs. 20.6 +/- 2.0 hours), reduced oxytocin infusion duration (10.0 +/- 2.1 vs. 20.0 +/- 2.3 hours. P less than 0.0001) resulting in a lower cesarean delivery rate, 26 vs. 47 per cent (P greater than 0.05). Thirty-two per cent of patients receiving the prostaglandin gel labored and delivered within 12 hours and required no oxytocin. In addition, the use of prostaglandin E2 gel appeared safe in that no patient experienced an untoward reaction. Two cases of uterine hyperstimulation occurred that required uterine tocolysis but were not associated with fetal distress. The use of prostaglandin gel appears to be a safe and effective method to improve cervical inducibility in patients undergoing induction for a variety of maternal and fetal indications.     

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.     

Intracervical application of prostaglandin gel for induction of term labor

A new gel for local application of prostaglandins has been elaborated. The new gel, based on a lyophilized prostaglandin E2 (PGE2) starch powder, seems to have solved most of the pharmaceutical and clinical problems associated with local administration of prostaglandins. In a randomized double-blind study, 50 nulliparous patients with an unfavorable cervical state at term were given 2 ml gel containing 0.5 mg PGE2 (PGE2 gel) or gel without PGE2 (placebo gel). The gel was deposited into the cervical canal. Among patients given PGE2 gel, 11 of 25 had induced labor, delivering without further stimulation within 24 hours. In patients given placebo gel, 2 of 25 were delivered with 24 hours. This difference is statistically significant (P less than .01). Patients undelivered after treatment with PGE2 gel achieved a considerable and statistically significant improvement of cervical score, whereas in patients in whom labor was not induced successfully by placebo gel treatment no significant changes in cervical score were registered. In a subsequent open study another 70 term patients of varied parity were given 0.5 mg PGE2 gel. Thirty-eight patients (54%) had successfully induced labor. Among the remaining undelivered patients, considerable ripening of the cervix occurred. Thus, the cervical score changed from a mean of 3.2 prior to treatment to a mean of 6.5 by 24 hours after treatment. Gastrointestinal discomforts were not observed. Signs of uterine hyperstimulation were registered in 1 patient.     

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.     

Prostaglandin E2 (PGE2) vaginal gel for cervical ripening

Cervical ripening prior to oxytocin stimulation is highly desirable to ensure a successful induction. Prostaglandin E2 has been administered by intracervical, intravaginal and extra-amniotic routes with successful ripening of the cervix. The dose of PGE2 administered is under investigation. Use of 3 or 4 mg of PGE2, although effective, has been reported to be accompanied by uterine hypertonus or fetal heart changes. Lower dose of PGE2 at 0.2 mg and 0.4 mg do not have the above-mentioned side effects but necessitate multiple applications. This randomized double-blinded study incorporated the use of 2 mg of PGE2 administered by intravaginal route in a hydroxyethyl cellulose gel medium. A significant increase in Bishop score (40% higher) was achieved in patients receiving PGE2 as compared to placebo patients. There were no adverse side effects, indicating application of 2 mg of PGE2 as a safe method of cervical ripening prior to induction of labor.     

Prostaglandin E2 gel induction of patients with a prior low transverse cesarean section.

To determine safety and efficacy of induction with prostaglandin E2 gel, we compared the outcome of 25 patients (study group) with an unfavorable cervix, a medical indication for delivery, and one prior low cervical transverse cesarean section to 56 patients (comparison group) with one prior low cervical transverse cesarean section and spontaneous labor. We placed 1 mg of prostaglandin E2 in gel intracervically in the 25 study patients. Common indications for delivery were: diabetes, post dates, and preeclampsia. Although most labor and delivery variables were similar, the study group had a longer mean latent phase (14.2 +/- 13.8 versus 7.3 +/- 3.7 hours: p less than 0.002), but had a shorter mean length of active phase (4.0 +/- 3.5 versus 5.7 +/- 3.0 hours; p less than 0.02). None of the patients in either group had a dehiscence of the uterine scar, nor rupture of the uterus. Both groups had a similar cesarean section rate. Since from the few reported, nonrandomized studies it appears that prostaglandin E2 gel use in patients with a prior low cervical transverse cesarean section may be useful and relatively safe, it may be time to attempt randomized trials of prostaglandin E2 gel versus oxytocin for induction of patients with a prior low cervical transverse cesarean section, unfavorable cervix, and a medical indication for delivery.     

Effect of beta-mimetic tocolysis on cervical ripening and plasma prostaglandin F2 alpha metabolite after endocervical application of prostaglandin E2

To suppress uterine contractions during cervical ripening induced by prostaglandin E2 (PGE2) gel, beta-mimetic drugs were given orally 30 minutes before PGE2 application to 17 patients with unripe cervix. This prevented the increase in contraction frequency observed during the first four hours after PGE2 application in 17 controls. Nevertheless, cervical ripening proceeded at a similar rate and the clinical outcome was comparable in both groups. Prostaglandin E2 application caused a transient rise in plasma levels of the PGE2 alpha metabolite (13,14-dihydro-15-keto), which was not prevented by pretreatment with beta-mimetics. Patients with premature rupture of the membranes had higher initial plasma PGF2 alpha metabolite levels than those with intact membranes but cervical ripening proceeded with the same rate, and the effect of beta-mimetics was the same in both groups. Thus, cervical ripening induced by PGE2 does not depend on uterine contractions, and increased production of PGF2 alpha is unrelated to the ripening process. There was no difference between the three beta-mimetic agents in the present study.