Oxytocin-induced labor characteristics and uterine activity after preinduction cervical priming with prostaglandin E2 intracervical gel

Labor characteristics and quantitation of uterine activity resulting from oxytocin induction of labor after intracervical prostaglandin E2 (PGE2) gel priming have not been previously reported. Forty-seven women with modified Bishop scores of 5 or less received preinduction priming with 0.5 mg of intracervical PGE2 gel. Oxytocin was used to induce labor after priming, and uterine activity was quantitated. A matched group of control patients was managed identically but did not receive PGE2 gel. In the gel group, modified Bishop scores improved significantly and in two patients (4%), priming alone induced labor. No uterine hyperstimulation or fetal heart rate abnormalities occurred during priming. Cesarean sections for all indications and those for failed induction were less common in the gel group. The length of the active phase and the second stage of labor were significantly shorter in the gel group. Uterine activity was similar in both groups. The data suggest a primary cervical action of the gel.     

Induction of labor by prostaglandin E2: intracervical gel or vaginal pessaries?

To investigate the best route of prostaglandin medication for induction of labor, 125 pregnant women with unfavorable cervices (Bishop scores less than or equal to 6) were randomized to induction of labor with either PGE2 (0.5 mg) in a viscous intracervical gel once daily or PGE2 pessaries (2.5 mg) 1-2 a day. As estimated by life table analysis, the pessaries were significantly more effective inducing vaginal delivery compared to intracervical gel (24 h: P less than 0.025, 48 h: P less than 0.01, logrank test) and vaginal delivery was obtained within 24 h/48 h in 50%/72% of the women in the pessary group and in 29%/55% of the women in the intracervical group. Cervical ripening was found within 3 h (P less than 0.001) and in the subsequent 3 to 24 h period (P less than 0.005) after both treatments, no difference being found between the groups. The pessaries were much more effective inducing regular contractions compared to the intracervical gel (P less than 0.005, logrank test), so the latter seems preferable if cervical ripening rather than induction is intended. No difference was found analyzing the active labor period. No difference was found in methods of delivery, neonatal parameters (Apgar scores, umbilical artery blood pH and standard base excess), and the patients' attitude towards both methods of induction were equally favorable.     

Prediction of cervical response to prostaglandin E2 using fetal fibronectin

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

Cervical ripening and induction of labor by intracervical and extra-amniotic prostaglandin gel application in cases of intrauterine fetal death

In 42 patients with intrauterine fetal death between the 29th and 43rd week of gestation, a standard, 2-step procedure was employed to deliver the dead fetus. After priming with an intracervical application of PGF2 alpha- or PGE2-gel, labor was induced by extra-amniotic prostaglandin (PG) gel or oxytocin infusion while under epidural anesthesia. Intracervical PG application led to a significant improvement in the modified Bishop score from 1.3 to 7.6 after a mean of 8 h. In 20 patients labor and progressive dilatation of the cervix occurred after intracervical PG gel application alone. The average total therapy time was 18.1 h in patients treated with PGF2 alpha and 13.7 h in the PGE2-treated group. The average induction of labor to delivery intervals were 8.8 h in the PGF2 alpha- and 7.1 h in the PGE2-group. Gastrointestinal side effects were observed in only 5 patients. The combination of cervical ripening with intracervical PG gel application and induction of labor by extra-amniotic PG gel under epidural anesthesia is an efficient and safe method for treatment of intrauterine fetal death.     

Intracervical prostaglandin in postdate pregnancy. A randomized trial

A study was designed to see if incorporating intracervical administration of prostaglandin could affect the outcome of postdate pregnancies. All patients with verified dates, at least 41 6/7 weeks pregnant and enrolled in an antepartum testing schedule were randomized in a double-blind fashion to receive either 0.5 mg of prostaglandin E2 (PGE2) suspended in methylcellulose or a placebo of the gel alone. The gel was inserted directly into the cervical canal after the patient had a reactive/negative contraction stress test. The patient was then observed on an external fetal monitor for an hour before going home. A total of 23 patients received PGE2, and 20 received the placebo. Results were analyzed for the following: change in the Bishop score, lag time from dosage to delivery, spontaneous versus induced labor, cesarean section rate, length of labor and neonatal outcome. There were no significant differences between the groups except in the incidence of patients going into labor within 72 hours. The results indicate that, in general, 0.5 mg of intracervical PGE administered at greater than or equal to 41 6/7 weeks without subsequent oxytocin induction of labor did not appear to significantly alter the obstetric outcome.     

Nonpharmaceutical ripening of the unfavorable cervix and induction of labor by a novel double balloon device

Artificial ripening of the unfavorable cervix was attempted in 48 women using intracervical prostaglandin (PG) E2 gel applied by a cannula and in 70 others by a newly designed double balloon device (Atad Ripener Device). In the first group (phase A), application of PGE2 gel by intracervical cannula resulted in a mean increase of 3 points in the Bishop score and a mean instillation-to-delivery time of 34.2 hours. The study of labor induction by the double balloon device was carried out in two parts. One (phase B) consisted of a double-blind randomized controlled study in which, through the double balloon device, ten women received PGE2 gel and another ten were given placebo gel. There was no significant difference in the increase of Bishop score between the two groups (5.8 points in the treatment group and 6.0 in the placebo-controlled group). Ninety percent of women in both groups delivered vaginally with a mean of 20.8 hours after device insertion. The third phase of the study consisted of an open trial of inserting the double balloon device alone without PGE2, and inflating the balloons in 50 patients. A mean increase of 4.4 points in the Bishop score was noted in these women. These findings suggest that the use of the double balloon device for ripening of the unfavorable cervix is an effective and well-tolerated method of labor induction.     

Weekly administration of prostaglandin E2 gel compared with expectant management in women with previous cesareans. Prepidil Gel Study Group.

OBJECTIVE: To compare the clinical effectiveness and safety of outpatient administration of intracervical prostaglandin (PG) E2 gel with expectant treatment for women desiring vaginal births after cesareans. METHODS: This was a randomized, multicenter investigation involving term pregnant women who each had one previous low-transverse cesarean and an unfavorable cervix (Bishop score no more than 6), and who was a candidate for vaginal delivery. They were assigned to receive 0.5 mg of PGE2, (Prepidil; Pharmacia-Upjohn, Kalamazoo, MI) intracervically at 39 weeks' gestation, repeated at weekly office visits for up to three doses, or expectant treatment. The main outcome variable was vaginal birth. RESULTS: Of 294 cases, 143 received gel and 151 were treated expectantly. No differences between groups were found for maternal age, race, or Bishop score. Compared with the expectant treatment group, the PGE2 gel group was not more likely to deliver sooner or vaginally (57% versus 55%, P = .68). The onset of labor, duration of labor among those delivering vaginally, and 1- and 5-minute Apgar scores were not different between groups. No uterine ruptures occurred, and adverse effects were equally likely in both groups. CONCLUSION: Although its safety was confirmed for outpatient use, weekly doses of intracervical PGE2 did not improve the likelihood of vaginal births after cesareans.     

Pre-induction intracervical application of a highly viscous prostaglandin E2 gel in pregnant women with an unripe uterine cervix: a double-blind placebo-controlled trial.

Intracervical application of prostaglandin E2 (PGE2) gel has shown to be an effective method for pre-induction cervical ripening in pregnant women with an unripe uterine cervix. Side effects are minimal, provided that the instillation is carefully restricted to the cervical canal. This requires--apart from a proper technique--an optimal gel formulation. For this reason a newly developed highly viscous PGE2 gel was evaluated in a randomized, double-blind, placebo-controlled multicentre trial. Within a 9-h study period, successful cervical ripening (increase in Bishop score to 6 or more) was achieved in 39 (56%) of the 70 patients in the PGE2 groups and in 23 (34%) of the 68% patients in the placebo group (P = 0.04). During the first 12 h after gel application, 25 (35%) of the women in the PGE2 group and 2 (3%) in the placebo group had a spontaneous delivery. No serious adverse reactions were observed. The data suggest that the use of this highly viscous PGE2 gel may be advantageous if strictly intracervical application is the primary objective.     

Labor characteristics of uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2 gel versus intravenous oxytocin.

Labor characteristics after intracervical application of 0.5 mg prostaglandin (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for labor induction were investigated in uncomplicated prolonged pregnancies with unripe cervix. The induction to delivery time as well as the total oxytocin dose were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections, instrumental deliveries and fetal distress had the same frequency, but the failures of trial were significantly higher in the oxytocin group than in the PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second PGE2 dose, and almost half of the women in the PGE2 group experienced 'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores < 7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous oxytocin in terms of shortening the induction-delivery interval and increasing the frequency of successful vaginal delivery. In addition, it is safe for mother and fetus.     

Misoprostol outpatient cervical ripening without subsequent induction of labor: a randomized trial

OBJECTIVE: To estimate the effect of outpatient administration of a single dose of vaginal misoprostol at term on the interval to delivery in women with unfavorable cervices. METHODS: Randomized, double blind, placebo-controlled trial comparing a single 25-microg outpatient intravaginal dose of misoprostol to placebo in pregnant women with Bishop scores less than 9 at 40 weeks or greater. After placement of the study medication, subjects were permitted to go into spontaneous labor unless an indication for induction developed. Analysis was by intent to treat. The interval to delivery, defined as the time from medication placement to delivery, was compared by Student t test and by survival analysis with the log-rank test. RESULTS: Thirty-three women were randomly assigned to receive misoprostol, and 35 were assigned to receive placebo. The mean interval to delivery was significantly less in the misoprostol group, 4.2 +/- 4.1 compared with 6.1 +/- 3.6 days, P =.04. The interval to delivery for only the nulliparous patients was significantly less in the misoprostol group, 4.2 +/- 4.0 compared with 7.2 +/- 3.7 days, P =.02. The survival curves for the interval to delivery were significantly different (P =.04 by log-rank test) with 4.1 days median interval to delivery for misoprostol compared with 9.2 days for placebo. There were no adverse outcomes in either group. CONCLUSION: A single 25-microg outpatient intravaginal dose of misoprostol is effective in decreasing the interval to delivery in women with unfavorable cervices at term.     

Influence of misoprostol or prostaglandin E(2) for induction of labor on the incidence of pathological CTG tracing: a randomized trial

OBJECTIVE: To compare the efficacy and safety of misoprostol (prostaglandin E(1) (PGE(1))) with dinoprostone (prostaglandin E(2) (PGE(2))) for third trimester cervical ripening and labor induction. STUDY DESIGN: Patients requiring induction of labor were randomly assigned to receive either 50 microg of intravaginal misoprostol every 4 h or 0.5 mg of intracervical dinoprostone gel every 6 h. Eligibility criteria included gestation = 36 weeks. Primary outcome was the time interval from induction to delivery; secondary outcomes were mode of delivery, perinatal outcome, and interpretation of cardiotocogram (CTG) records. RESULTS: Two hundred women were randomly enrolled to receive either misoprostol (n = 100) or dinoprostone (n = 100). Time induction-to-delivery at 12, 24 and 48 h and the need for oxytocin were reduced with misoprostol (P < 0.05). Pathological CTG tracing according to FIGO and Melchior scores were more frequent in the misoprostol-treated group (P < 0.001). CONCLUSION: Misoprostol shortened the induction-to-delivery interval, but is associated with a higher incidence of abnormal CTG than prostaglandin E(2).     

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.     

Predictive value of pelvic scores for induction of labor by local PGE2.

The predictive value of pelvic scores, parity, age and gestational age for induction of labor by local prostaglandin-E2 (PGE2) was examined in 336 women attempting induction of labor by intracervical or vaginal PGE2. The patient characteristics were correlated to: (1) vaginal delivery within 48 h, (2) the period from induction to onset of labor (latency period), and (3) the duration of labor. The Bishop score (P < 0.01) and even more the Lange score (P < 0.0001) were significantly inversely correlated to both latency period and induction-delivery period. This was caused by cervical dilatation (P < 0.001), fetal station (P < 0.05) and cervical length (P < 0.05), whereas position and consistency of the cervix were of no importance. All three periods studied were significantly (P < 0.0001) shorter in parous women. In primiparous women, gestational age was of no importance for the latency period; however, higher gestational age was associated with longer labor (P < 0.001). We conclude that the predictive value of pelvic scores on induction hardly differs using local PGE2 compared to conventional methods; furthermore, the Bishop score should be substituted, disregarding position and consistency of the cervix, but putting more weight to cervical dilatation. A new pelvic score is proposed.     

Determinants of response to intracervical prostaglandin E2 for cervical ripening. Gruppo di Studio sull'Induzione del Travaglio di Parto

OBJECTIVE: To analyze the determinants of response to intracervical prostaglandin E2 (PGE2) in cervical ripening. STUDY DESIGN: A total of 250 women with normal pregnancy, parae three or less, with intact membranes between 40 and 42 weeks of gestation and Bishop's score < or = 4 were treated with 0.5 mg PGE2 intracervical repeated after 12 hours if cervical Bishop's score was still < or = 4. RESULTS: After the first administration of PGE2, labor was induced in 106 (42.4%) women. Nulliparae had a significant longer interval from the first PGE2 dose to delivery and more failures of treatment and caesarean sections than parae. There was a tendency towards a shorter interval between the first administration and delivery and a decrease in the frequency of treatment failures with increasing Bishop's score, but the finding was not statistically significant. No fetal or neonatal death occurred. There were eight neonates at one min and three neonates at five min with an Apgar score less than seven. There were 22 neonates admitted to Neonatal Intensive Care Unit. There were 20 cases of jaundice. CONCLUSIONS: The study confirms that the main determinant of treatment failure with PGE2 gel in cervical ripening is nulliparity.     

Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study

Forty primigravid women due to undergo first trimester termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E2 in gel or gel only as placebo. In the PGE2-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of 11.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE2-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15%) patients, fetal demise was observed. The mean induction-abortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE2-gel group. Termination of pregnancy was found to be easier in the PGE2-gel group, compared to the placebo group.     

Preinduction cervical ripening techniques compared

OBJECTIVE: To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening. STUDY DESIGN: From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables. RESULTS: Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups. CONCLUSION: The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.     

Cervical ripening with prostaglandin gel and hygroscopic dilators.

OBJECTIVE: To study the effectiveness and morbidity of adding hygroscopic cervical dilators to prostaglandin gel for cervical ripening and labor induction. STUDY DESIGN: Patients of at least 34 weeks' gestation with a medical indication for induction of labor and with a modified Bishop score of 5 or less were randomized to receive either prostaglandin gel or prostaglandin gel with hygroscopic cervical dilators. Primary outcomes were time to delivery, change in cervical score, and infection. Secondary outcomes included cesarean delivery rate and deliveries before 24 hours of induction. Continuous variables were analyzed by Wilcoxon sum rank test and categorical data by chi-square or Fisher exact test, with P < 0.05 being significant. RESULTS: Seventeen patients were randomized to intracervical prostaglandin alone and 23 patients received intracervical prostaglandin plus hygroscopic dilators. No demographic differences were noted between the groups. After six hours of ripening, the combined group achieved a greater change in Bishop score (3.6 vs. 2.1, P = 0.007) and tended to have a shorter induction time (21.7 vs. 26.4 hours, P = 0.085). The combined therapy group had a higher infection rate than the prostaglandin-only group (59% vs. 12%, P = 0.003). CONCLUSION: Combining cervical dilators with prostaglandin gel provides more effective cervical ripening and a more rapid induction to delivery interval than prostaglandin alone but with a significant and prohibitive rate of infection.     

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.     

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.     

Preinduction cervical ripening with prostaglandin E2 intracervical gel

A double-blind, placebo-controlled, dose-ranging study was undertaken to evaluate the efficacy of two doses of intracervical prostaglandin E2 gel in patients with unfavorable Bishop scores. Mean change in Bishop score, success of softening, time to labor, and time to delivery were all significantly different in the two treatment groups as compared with the placebo group. Twenty-three of 30 treated patients had uterine contractions lasting greater than four hours and eight patients delivered during the observation period. Moreover, one case of uterine hyperactivity and five cases of severe fetal heart rate decelerations were noted in the treatment groups. Although efficacious for cervical ripening, caution is warranted when using this technique in patients at risk for placental insufficiency.