Induction of labor in postterm pregnant women

We have studied the outcome of labor induction in 145 postterm pregnant women in whom gestational age was properly assessed by ultrasound scanning. The induction techniques were adapted to the cervical states of the patients. Seventy-five patients (32 nulliparous and 43 multiparous) with favorable cervical states were successfully induced with intravenous oxytocin. In this group the frequency of Caesarean section was 2%. Seventy patients (45 nulliparous and 25 multiparous) with unripe cervices received 0.5 mg PGE2 in viscous gel intracervically to prime the cervix and to induce labor; 38 (52%) were induced into labor after a single PGE2-gel application whereas 26 (48%) needed labor augmentation with intravenous oxytocin after PGE2-gel obtained cervical ripening. In 6 of the 20 patients the cervix did not ripen and the PGE2-gel application had then to be repeated. The frequency of cesarean sections was 11%. In 5 out of the 145 patients (4%) the fetuses had signs of intrauterine growth retardation (IUGR) as assessed by ultrasound scanning, and postmaturity as verified by pediatric examination at delivery. All these fetuses belonged to nulliparous women with unripe cervices and all had to be delivered instrumentally (3 by cesarean section and 2 by ventouse) indicating the fragility of these children. If postterm pregnancy is complicated by an unfavorable cervical state intracervical application of PGE2-gel seems to be an efficient method to prime the cervix and to induce labor. In most patients an uncomplicated vaginal delivery can be achieved by this procedure. However, nulliparous women with unfavorable cervices and signs of IUGR constitute a high risk group of patients at labor induction.     

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

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

Prostaglandin E2 cervical ripening without subsequent induction of labor.

OBJECTIVE: To determine whether outpatient administration of intracervical prostaglandin (PG) E2 gel decreases the interval to delivery and duration of labor. METHODS: A randomized, double-blind, placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks' or greater gestation with Bishop scores less than 9. Transvaginal cervical length, fetal fibronectin, and Bishop score were assessed before gel placement. Subjects were then allowed to go into spontaneous labor unless an indication for induction developed. RESULTS: Thirty women were assigned to PGE2 and 31 to placebo. There were no significant demographic differences between the groups and there were no differences in cervical length, fetal fibronectin status, or Bishop scores. Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement (P = .007). The median interval to delivery was significantly shorter in the PGE2 group, at 2.5 days, compared with placebo, at 7 days (P = .02). Nulliparas in the PGE2 group had a median interval to delivery of 2 days, compared with 7 days for nulliparas receiving placebo (P = .03). Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2. CONCLUSION: Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor.     

Intracervical application of PGE2-gel combined with early intravenous infusion of oxytocin for induction of term labor in women with unripe cervix

Fifty-four women with an unripe cervix at term were given 0.5 mg intracervical prostaglandin E2 (PGE2) gel. In 37 of them (70%) the cervix ripened within 5 h and seven of them were in labor at that time. Of the remaining 30 patients, 15 were randomly given an i.v. oxytocin infusion and 13 were delivered within 12 h. In 17 women (30%) the cervix was still unfavorable 5 h after PGE2-gel application but seven of them had a favorable cervix when reassessed 24 h after PGE2-gel instillation. All these patients went into labor with an i.v. infusion of oxytocin. The remaining 10 patients required another dose of PGE2-gel and subsequent i.v. oxytocin. Only in two of these patients did induction fail so that delivery by Caesarean sections was required. All infants were born in good condition.     

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.     

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.     

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.     

The efficiency of prostaglandin E2 vaginal suppositories versus intracervical prostaglandin gel for induction of labor in patients with unfavorable inducibility prospects

Two different applications of prostaglandin E2 for induction of labor were randomly used in 113 women with an unripe cervix; 57 women were given prostaglandin suppositories each containing 2.5 mg PGE2 in a basis of Witepsol S55 (Dynamit Nobel), another 56 women were treated with intracervical gel containing 1 mg PGE2 in 5 g hydroxypropylmethyl cellulose. The treatment was repeated after 4 h if the cervix was still unripe, and the procedure was repeated the following day if the cervix was still unfavorable. Cesarean sections was performed within 48 h after the start of induction and before the second stage of labor in 8 women in the suppository group and 7 women in the intracervical gel group. Of the remaining 98 women, 73% (34/48 women) in the suppository group and 36% (18/50 women) in the cervical gel group had delivered within 24 h (p less than 0.01). After 48 h, 88% (42/48 women) in the suppository group and 74% of the women (37/50 women) in the cervical gel group had delivered (p greater than 0.05). The induction-delivery interval in the suppository group was half that found in the cervical gel group. There was no significant difference between the two groups in the use of instrumental vaginal deliveries and cesarean sections nor was there any difference with regard to fetal distress. The post-delivery condition of the newborn was similar in the two groups. No side-effects were reported in either of the two groups.     

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.     

Preinduction cervical ripening: A randomized prospective comparison of the efficacy and safety of intravaginal and intracervical prostaglandin E2 gel

OBJECTIVE: The purpose of this study was to compare the effectiveness and safety of vaginally administered 5 mg prostaglandin E₂ gel prepared in our hospital pharmacy with a commercially available 0.5 mg intracervical prostaglandin E₂ gel.STUDY DESIGN: Eighty-three patients undergoing labor induction were randomly assigned to one of two groups for cervical ripening. Either a preparation of 5 mg of prostaglandin E₂ was placed vaginally or a commercially available 0.5 mg of prostaglandin E₂ was placed intracervically. A maximum of three doses at 6-hour intervals was administered before oxytocin was begun.RESULTS: Among the 83 patients evaluated, 44 were given vaginal gel and 39 were given intracervical gel. No statistically significant differences were observed between the two treatment groups with respect to the incidence of spontaneous versus induced labor, need for oxytocin augmentation, gel-to-induction interval, Bishop score change, maximum oxytocin dose, maximum dilatation rate, length of labor, cesarean section rate, fetal Apgar scores, fetal umbilical vein pH, or fetal umbilical artery pH.CONCLUSIONS: The two prostaglandin E₂ formulations appear equivalent in efficacy and safety. Constraints placed on intracervical prostaglandin E₂ gel make the vaginal preparation a desirable choice. (Am J Obstet Gynecol 1997;176:1305-12.)     

Ripening of the uterine cervix and induction of labour at term with prostaglandin E2 in viscous gel.

In order to achieve ripening of the uterine cervix or induce labour in patients at term with an unfavourable cervical state, 1 mg of prostaglandin E2 (PGE2), suspended in a viscous gel, was instilled into the cervical canal. In a pilot study, 41 patients received the PGE2-gel. Twenty-three of these, (56%), went into labour, and delivery occurred without further stimulation within 15 hours. In the remaining 18 patients, there was a marked improvement of the cervical state, which changed from an average (modified) Bishop score of 2.5 to 6.1 within 24 hours. In a double-blind study comprising 20 nulliparae, 10 received gel containing PGE2 and 10 gel without prostaglandin. Cervical state did not change significantly (Bishop score 3.6 and 4.0) after 24 hours in patients receiving placebo gel. In those receiving PGE2 gel, 8 went into labour and were delivered without further induction within 13 hours. Two patients showed an increase in Bishop score from 3 to 6 and 7, respectively, after 24 hours. They were then induced by oxytocin and delivery occurred after 8 and 10 hours. The results suggest that administration of PGE2 intracervically can induce ripening of the cervix in patients at term with an unfavourable cervical state, and thus facilitate delivery.     

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.     

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.     

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.     

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.     

Intracervical instillation of PGE2-gel in patients with missed abortion or intrauterine fetal death

A single intracervical instillation of prostaglandin E2 (1.0 mg or 0.5 mg in viscous gel) was given to dilate the cervix before dilatation and evacuation in patients with missed abortion or intrauterine fetal death in late pregnancy. The 1.0-mg dose of PGE2 gave more prominent cervical dilatation in early pregnancy. In late pregnancy 1.0 mg PGE2 induced labor in the majority of patients and with shorter induction delivery time than in patients given 0.5 mg PGE2. There was no uterine hypertonus and no patients complained of gastrointestinal symptoms. We conclude that intracervical instillation of 1.0 mg of PGE2 in viscous gel is a safe and effective method both for dilating the cervix before dilatation and evacuation and as a method of inducing labor in patients with intrauterine fetal death.     

Intracervical prostaglandin E2 gel. Safety for outpatient cervical ripening before induction of labor.

Cervical ripening prior to induction of labor is often necessary for medical complications of pregnancy. We proposed to prospectively determine the safety of administering prostaglandin E2 (PGE2) gel intracervically in an outpatient setting. Four hundred forty-six patients underwent 515 gel procedures as outpatients. Trained perinatal nurses placed 0.5 mg of PGE2, prepared in a standard methylcellulose base, in the intracervical canal. The PGE2 dose was administered every two hours for a total of three doses if labor did not start. The patient was sent home two hours after the last dose if she was not in active labor. Labor started in 90 patients (20%) during the gel procedure; they were admitted to the labor-and-delivery unit. The remaining patients were discharged. Eighty-eight patients (20%) were later admitted in active labor prior to scheduled induction. One patient (0.02%) was found to have occasional prolonged decelerations on admission and underwent a cesarean section two hours after admission; the Apgar scores were 8 and 9 and the arterial pH, 7.21. Hyperstimulation with excessive intrauterine activity caused significant deceleration of the fetal heart rate in four patients (0.8%), two of whom required transfer to the labor-and-delivery unit but none of whom needed a cesarean section for fetal distress. PGE2 gel can be administered safely intracervically as an outpatient procedure by trained perinatal nurses.     

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.     

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

A double-blind, randomized, placebo-controlled study was undertaken to evaluate the efficacy of a single-dose, shelf-stable preparation of prostaglandin E2 gel (PGE2) when used intracervically in patients with low Bishop scores. Two different preparations (0.5 and 0.25 mg) of PGE2 were used and a total of 45 patients were studied. Both preparations of PGE2 demonstrated a statistically significant increase in the spontaneous labor rate as compared with the placebo gel. Bishop scores were altered in all patients not proceeding to labor spontaneously, but the changes were most significant in the low- and high-dose groups. No significant deleterious affects were noted. The efficacy and safety of this new, sterile, and stable preparation makes it suitable for clinical use.     

Induction of labor with mifepristone--a randomized, double-blind study versus placebo.

OBJECTIVE: To evaluate the efficacy of mifepristone in inducing labor in women with an unripe cervix, its effect on the cervix and on the status of the newborn. METHODS: In a prospective double-blind study, 36 post-term pregnant women with a Bishop score of 5 or less received either 400 mg mifepristone (n=24) or placebo (n=12). If, 48 hours after the treatment was started, labor had not begun or the Bishop score was 5 or less, the women were given 0.5 mg prostaglandin E2 intracervically, a treatment which was repeated 12 hours later, if necessary. RESULTS: During the first 48 hours following treatment, 19 (79.2%) of the women treated with mifepristone and two of the women (16.7%) treated with placebo went into labor. In addition, one and three women, respectively, had a ripe cervix at the end of the 48h period. The overall success rate was thus 83.3% for mifepristone and 41.7% for placebo (p=0.008; OR 14.8; 95% CI 2.1-107.6). The median time from the start of treatment to delivery was also shorter (mifepristone 36h23' and placebo 53h17'). Treatment with intracervical PGE2 was needed more often after the placebo. The duration of labor, however, tended to be shorter after placebo than after mifepristone in the women who delivered vaginally. The frequencies of instrumental delivery were similar in both treatment groups. The median Apgar score was slightly lower at 1 minute (p<0.05) following mifepristone treatment, but did not differ at 5 and 10 minutes. There was no difference between the two treatment groups in the umbilical pH at delivery. CONCLUSION: The results of the present study show that mifepristone is a simple and effective treatment for inducing labor in post-term women with an unripe cervix.