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.     

Intravenous administration of prostaglandin F2alpha or prostaglandin E2 in labor pain induction in fetal death

Successful treatment of intrauterine fetal death by intravenous administration of (PGF2alpha) prostaglandin F2alpha in 20 patients (gestational age 22-40 weeks) and of PGE2 in 6 patients (gestational age 24-36 weeks) is reported. Infusion of 5-20 mcg PGF2alpha/minute and of 0.5-2.0 mcg PGE2/minute resulted in regular uterine contractions within the first 2 hours. The average dosage of PGF2alpha was 7.06 mg in cephalic presentations (infusion time=7 hours, 2 minutes) and 23.4 mg in anomalous presentations (infusion time=16 hours, 54 minutes). The average dose of PGE2 was 1.17 mg (infusion time=9 hours, 23 minutes). Coagulation investigations were performed before, during, and after PG infusion. These investigations suggest that the coagulation potential of patients with intratuerine fetal death by intravenous PG administration is not influenced to any extent. Few undesirable side effects were seen using this PG. We consider that the intravenous PG application for the induction of labor in intrauterine fetal death is a useful method because of the effectiveness and few undersirable side effects. (author's)     

Midtrimester abortion by intracervical prostaglandin E2

Seventy-six consecutive patients undergoing midtrimester abortion were randomly divided into treatment with either intracervical and (less so) extraamniotic prostaglandin E2 (PGE2) gel or intraamniotic prostaglandin F2 alpha (PGF2 alpha). At the end of 5 h the initial treatment was supplemented by an oxytocin drip and in the PGE2 group the intracervical application of gel was repeated if necessary. The second day a third application of PGE2 gel was administered to a few women. The two groups were comparable with regard to age, parity and gestational age. There was no statistical difference between the two groups in success rate during the 48 h study period (93% for PGE2 versus 97% for PGF2 alpha) or in the average induction-to-abortion interval (16.8 h for PGE2 versus 16.6 h for PGF2 alpha). The frequency of completed abortions was statistically significantly higher and the gastrointestinal side-effects significantly lower in the PGE2-treated patients as compared to the PGF2 alpha-treated subjects. Further, there were fewer complications and the pethidine consumption in women treated with intracervical PGE2 was lower as compared to patients treated with intraamniotic PGF2 alpha. In conclusion, an intracervical PGE2 gel is found applicable and more advantageous than intraamniotic PGF2 alpha in midtrimester abortion. It is safe, convenient and equally easy to administer during the early and the later parts of the second trimester.     

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.     

Combined intracervical PGE2 and intra-amniotic PGF2 alpha for induction of 2nd trimester abortion

Fourteen consecutive patients (mean gestational age 18.1 weeks, range 15-23 weeks) referred for therapeutic termination of pregnancy were induced into abortion by intra-amniotic PGF2 alpha 40 mg followed by oxytocin stimulation. 14 other patients (mean gestational age 17.9 weeks, range 15-23 weeks) were pretreated with intracervical PGE2 1.0 mg in gel for 4 h prior to induction of abortion with intra-amniotic PGF2 alpha 40 mg without further stimulation. The induction-abortion interval for patients treated with intra-amniotic PGF2 alpha and oxytocin, was 19.1 +/- 2.94 h (+/- SE, n = 14) with a success rate of 80% after 24 h. After pretreatment with intracervical PGE2 1.0 mg in viscous gel, intra-amniotic PGF2 alpha 40 mg induced abortion after 11.2 +/- 1.12 h (+/- SE, n = 14) with a 100% success rate after 24 h. No systemic side effects of the PGE2 pretreatment were noted. No cervical laceration was observed. The results need further confirmation, but still suggest cervical priming with intracervical PGE2 1.0 mg in gel and subsequent induction of abortion by intra-amniotic PGF2 alpha 40 mg as an attractive principle for 2nd trimester abortion.     

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 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.     

Labor induction with vaginal misoprostol and extra-amniotic prostaglandin F2alpha gel.

OBJECTIVE: To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostaglandin F2alpha (PGF2alpha) gel for induction of labor. METHOD: A randomized controlled trial, with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg, was conducted in Harare Maternity Hospital. A total of 152 women were admitted for induction of labor with a term singleton, pregnancy and cephalic presentation were recruited. The main outcome was duration of induction. RESULTS: There were no differences in the characteristics of women in the two groups at recruitment. In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin (OR=0.36; 95% C.I. 0.17-0.73) and delivery by cesarean section for failure to progress (OR=0.11; 95% C.I. 0.00-0.88). The risk for duration of induction to vaginal delivery exceeding 12, 18 or 24 h was reduced by 18%, 38% and 68%, respectively, but only the risk for duration >24 h was significantly reduced (OR=0.32; 95%C.I. 0.11-0.91). The mean duration of induction was shorter in the misoprostol group, 15.2 vs. 23.6 h (P=0.02). There were no differences in fetal outcome. CONCLUSION: Misoprostol 50 microg was associated with less use of oxytocin in labor, a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel.     

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.     

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.     

Extra-amniotic prostaglandin E2 for midtrimester termination of pregnancy in live fetuses vs. fetal demise

This study compared the course of midtrimester termination of pregnancies with fetal demise and those with a viable fetuses by extra-amniotic prostaglandin (PG) E₂. A total of 275 women who underwent second trimester abortion with extra-amniotic PGE2₂ were divided into two groups: 95 patients (35%) with fetal demise and 180 women (65%) with a live fetuses. Extra-amniotic PGE2₂ was administered in doses of 200 μg every 2 h up to 20 doses. Bumm curettage was performed in the majority of the patients. We compared the duration and complication rate between the groups. The median induction to abortion interval was significantly shorter in the fetal demise group (13 vs. 21 h) than in the live fetus group. Mean gestational ages and complication rates were similar. Midtrimester termination of pregnancy with extra-amniotic PGE2₂ is a safe method with a low complication rate. In cases of pregnancy with fetal demise extra-amniotic PGE2₂ is associated with a significantly shorter induction to abortion interval than with a live fetus.     

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.     

Extra-amniotic saline, laminaria, or prostaglandin E(2) gel for labor induction with unfavorable cervix: a randomized controlled trial

OBJECTIVE: To determine which of three methods of cervical ripening resulted in the lowest cesarean rate in women with unfavorable cervices and indications for labor induction. METHODS: Consenting women with singleton gestations, vertex presentations, and unfavorable cervices (dilatation under 2 cm and effacement under 75%) were randomly assigned to laminaria and standard intravenous oxytocin, serial doses of intracervical prostaglandin (PG) E(2) gel (Prepidil, Pharmacia & Upjohn, Inc., Kalamazoo, MI) 0.5 microg every 6 hours for two doses followed by oxytocin if indicated, or extra-amniotic saline infusion and oxytocin. RESULTS: An interim analysis after recruitment of 321 subjects, 67% of the planned sample, found similar cesarean rates for the three groups (laminaria 36%; PGE(2) gel 33%; saline infusion 29%; P =.59); however, the mean randomization-to-delivery interval was significantly longer in the PGE(2) group. Stochastic curtailment, as part of the interim analysis, indicated a low likelihood of achieving a statistically significant difference in cesarean rates between PGE(2) gel and the other two groups. Therefore, we completed the study with saline infusion and laminaria. The saline infusion and laminaria groups had similar preinduction characteristics. The cesarean rates were similar (saline infusion 25.4% versus laminaria 30.3%; P =.32), but the mean interval from randomization to delivery was shorter in the saline infusion group (18.0 versus 21.5 hours, P =.002). There were no significant differences in selected maternal and neonatal morbidities. CONCLUSION: Cervical ripening with extra-amniotic saline infusion, PGE(2), or laminaria resulted in comparable cesarean rates in women with an unfavorable cervix and indications for labor induction. Extra-amniotic saline infusion had the shortest randomization-to-delivery interval without increasing maternal or neonatal morbidity.     

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.     

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.     

Optimal Interval Between Prostaglandin E2 Ripening of the Cervix and Oxytocin Induction of Labor: A Prospective Clinical Trial

Does altering the interval between prostaglandin E₂ (PGE) gel application and oxytocin administration shorten induced labor without loss in efficacy? A prospective clinical trial was completed for 133 clinic patients who were candidates for the induction of labor with an unfavorable cervical status. All patients were randomly allocated to receive intracervical PGE gel 0.5 mg either 6 h or 1 h prior to the standardized administration of oxytocin. Repeat gel application and serial-day induction were offered to those judged medically stable who continued to meet inclusion criteria.

The gel to delivery duration was significantly shortened when comparing the 6-h interval to the 12-h interval only among single-day induction patients (P = 0.004) and was associated with a nonsignificant trend toward higher rates of failed induction and cesarean delivery (P = 0.073). When all patients are included, no difference between the groups was observed in the progress or outcome of labor.

A 6-h interval between PGE and oxytocin will shorten the interval to vaginal delivery only when labor is limited to a single-day attempt, but with a probable increased risk of failed induction and cesarean delivery.     

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.     

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.     

Induction of dead fetus labor with 15-(S)-methyl prostaglandin F2 alpha

This study examines whether labor can be induced with the intramuscular administration of 15-(S)-methyl prostaglandin F2 alpha in cases of intrauterine fetal death. The success rate of labor induction in the studied group was 93.75%, and was the same for primigravid and multigravid patients. The authors conclude that the prophylactic administration of an analgesic potentiator, an anti-emetic and an anti-diarrheal is advantageous to a woman's tolerance of the prostaglandin. PGF2 alpha is a quick and effective drug for use in the induction of labor to terminate pregnancies with intrauterine fetal death and offers tolerable side-effects when used with adjuvant medication.     

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.