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.     

Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix

In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.     

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.     

Induction of labor with intravenous oxytocin or vaginal PGE2 suppositories. A randomized study

Thirty-eight term pregnant women with a moderately unfavorable cervix (cervical score 4-5 p.) were randomly given intravenous oxytocin (Group A) or 3 mg PGE2 as a vaginal suppository (Group B) for labor induction. Eight out of 19 in Group A and 17 out of 19 in Group B gave birth vaginally within 24 h. The remaining 11 women in Group A had still an unfavorable cervix after 24 h. They were then given 3 mg PGE2 as a vaginal suppository and all but one had given birth vaginally without complications within 24 h. In Group B only 2 were still undelivered after 24 h. Both had a favorable cervix and were delivered vaginally within 12 h after intravenous infusion of oxytocin. The number of instrumental deliveries in Group A was one cesarean section and two vacuum extractions and in Group B three vacuum extractions. One woman in Group B reported nausea and vomiting and in one had strong uterine contractions in the second stage of labor. Otherwise no side effects were registered. All babies were born in good condition with Apgar scores greater than or equal to 7. In conclusion, vaginal application of 3 mg PGE2 as a suppository seems to be more effective than intravenous infusion of oxytocin for labor induction in women with half-ripened cervices, i.e. cervical scores of 4-5 p.     

Cervical priming and labor induction with vaginal application of 3 mg PGE2 in suppositories in term pregnant women with premature rupture of amniotic membranes and unfavorable cervix

Sixty-one term pregnant women, 29 nulliparous (Group A) and 32 multiparous (Group B) with unfavorable cervix and premature rupture of the membranes (PROM) were given 3 mg PGE2 in suppository form for cervical ripening and labor induction. Five hours after starting the treatment, 12 women of the 29 in Group A and 21 of the 31 in Group B had a favorable cervix and established labor. The remaining 17 nulliparae and 11 multiparae still had an unfavorable cervix and were then given another PGE2 suppository. Until the next morning, i.e. within 24 h, 19 nulliparous and 22 multiparous women gave birth whereas a further 5 nulliparous women who now had favorable cervix but no uterine contractions were delivered after stimulation with intravenous oxytocin. The remaining undelivered women were given another PGE2 suppository. With or without additional oxytocin stimulation, all but 2 multiparous women could be delivered within a further 12 hours. The total number of instrumental deliveries in Group A was 2 caesarean sections due to disproportion (7%) and 5 ventouses. In Group B, 3 caesarean sections (9%) had to be carried out, one due to fetal distress and 2 due to failed induction. From the results of this study we conclude that vaginal application of 3 mg PGE2 in suppository form can be used to induce labor in patients with PROM and unripe cervix. However, when the results are compared with those obtained in previous studies after application of PGE2 in gel, the latter technique seems preferable.     

缓释型前列腺素E2栓用于足月妊娠引产的临床观察

目的 :研究缓释型前列腺素E2 栓用于足月妊娠引产的有效性及安全性。方法 :随机单盲安慰剂对照研究。选择 2 0例 2 5～ 34岁单胎足月无引产禁忌证产妇 ,随机分为用药组 (10人 )和安慰剂组 (10人 )。记录宫颈Bishop评分、用药至临产时间、2 4小时引产成功率、经阴道分娩率、新生儿Apgar评分和产后出血量等。结果 :用药组 4小时宫颈成熟 ,用药至临产平均 8小时 5 5分钟 ,引产成功 9例 ,经阴道分娩率 7例 ,新生儿Apgar评分 1分钟全部 10分 ,产后出血量平均15 5ml;安慰剂组宫颈无变化 ,引产全部失败。结论 :首次于国内通过小样本临床观察后 ,认为缓释型前列腺素E2 栓用于足月引产效果好 ,副反应小 ,使用方便而安全     

Open randomized comparison of prostaglandin E2 given by intracervical gel or vagitory for preinduction cervical ripening and induction of labor.

Intracervical application of prostaglandin E2 (PGE2) in a viscous gel was compared with conventional wax-based PGE2 vagitories (pessaries) for ripening of the cervix prior to induction of labor. A total of 226 healthy pregnant women at term were randomly allocated to receive intracervical gel with an effective dose of 0.5 mg (n = 116) or vagitories containing 2.5 mg PGE2 (n = 110). All women had a modified cervical score of less than or equal to 4. The numbers of cases contributed by each of the three centers were similar. There was no significant difference in parity, gestational length, maternal characteristics, indications for induction or preinduction cervical scores between the treatment groups. The rate of spontaneous birth was 71% in the gel group, compared with 69% in the vagitory group. Successful treatment was defined as active labor within 24 h or a change in cervical dilatation allowing artificial rupture of the membranes with subsequent progressive labor. The success rate was not significantly different in the gel group (82%) compared with the vagitory group (80%). There were no differences in the frequency of fetal distress, outcome of labor, assisted delivery rates or maternal side effects. The cervical scores were not different at 12 and 24 h after application. Intracervical gel and intravaginal application of PGE2 were similar in their efficacy and safety for ripening of the cervix and inducing labor at term.     

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.     

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.     

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.     

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.     

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.     

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.     

Influence of preinduction prostaglandin E2 vaginal gel on cervical ripening and labor

A sterile gel containing prostaglandin (PG) E2 (2 mg PGE2 10 ml gel) was instilled vaginally in 65 primigravidas with unripe cervixes to accelerate ripening before planned surgical induction of labor. The patients treated with the gel were compared with 30 similar untreated controls. In the PGE2-treated group a significant improvement on cervical score was achieved before labor began, and 47% began to labor "spontaneously" without further treatment. Both the duration of subsequent labor and the incidence of cesarean section were significantly lower in the PGE2-treated group. There were no unwanted fetal or maternal effects. Pretreatment with intravaginal PGE2 gel reduces the risk of failed induction and provides the mother with an experience similar to spontaneous labor without harming the fetus.     

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.     

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.     

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.     

Premature rupture of membranes near term: induction of labor with endocervical prostaglandin E2 gel or intravenous oxytocin

We have studied the influence of endocervical application of 0.4 mg prostaglandin E2 (PGE2) in gel on the clinical outcome of pregnancies of at least 36 weeks' duration complicated with premature rupture of the membranes (PROM) and unripe cervix, (modified Bishop score of 7 or less). There were 579 women in the study. The PGE2 gel was applied within the first 12 hours after PROM. The first 60 women were randomly divided into controls given oxytocin infusions and experimental subjects given PGE2 gel. All others were given PGE2 gel, and the results were compared with those obtained in patients with similar criteria who were treated with oxytocin infusions during the preceding year. The clinical outcome was significantly better in the PGE2-treated patients than oxytocin-infused patients. PROM to delivery interval and the incidence of operative deliveries were significantly reduced. No adverse effects on the neonates were observed and the incidence of neonatal infection declined. It is concluded that cervical ripening with PGE2 gel in patients with PROM and unripe cervix near term significantly improves the outcome for both mother and child.     

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.     

Fetal circulation 60 to 80 minutes after vaginal prostaglandin E2 in pregnant women at term

We combined real-time B-mode ultrasonography with a 2 MHz pulsed Doppler technique to record blood flow in the fetal descending aorta and in the intra-abdominal part of the umbilical vein in 14 pregnant women at term. The blood flow was studied before and after instillation into the vagina of either 4 mg prostaglandin E2 (PGE2) gel or placebo gel. The PGE2 gel was significantly more effective in cervical priming and labor induction than the placebo gel. After instillation of the gel neither group showed a change in the fetal volume blood flow or in the aortic blood velocity waveform. We conclude that the instillation of 4 mg of PGE2 gel does not affect fetal hemodynamics at term.