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.     

Double-blind comparison of intravaginal prostaglandin E2 gel and "chip" for preinduction cervical ripening

The intravaginal application of prostaglandin E2 for preinduction cervical ripening has proved to be advantageous in the management of patients with an unfavorable cervix. The purpose of this double-blind randomized investigation was to compare the efficacy and safety of two methods of prostaglandin E2 delivery. Patients who were to have preinduction cervical ripening because of an unfavorable cervix (Bishop score less than or equal to 4) were randomly assigned to be given a single dose of prostaglandin E2 as either 2.5 mg of gel or a 3.0 mg "chip" intravaginally in a placebo-controlled manner. Sixty-nine patients received the active prostaglandin E2, 34 in the gel group and 35 in the "chip" group. The groups were similar in maternal age, race, parity, gestational age, and initial Bishop score. Both forms of prostaglandin E2 were easy to administer and helpful in priming an unfavorable cervix. The need for, duration of, and maximum dose of oxytocin were similar in both groups. Cesarean delivery because of failed induction occurred in 5 of 35 (14.3%) patients receiving a "chip" and 4 of 34 (11.8%) receiving the gel. However, patients receiving a "chip" experienced a 20% (7/35) incidence of hyperstimulation, compared with 2.9% (1/36) in those receiving the gel (p less than 0.05). The only case requiring immediate cesarean delivery because of intractable uterine hyperstimulation received a "chip." We conclude that both methods were effective for cervical ripening, but the lower incidence of uterine hyperstimulation seen with the gel would suggest that it is preferable to the "chip."     

A comparison of four methods of ripening the unfavourable cervix.

A comparison was made between four methods of ripening the unfavourable cervix (extra-amniotic prostaglandin E2 gel, oral prostaglandin E2, intravaginal prostaglandin E2 and intravenous oxytocin) in a clinical trial involving 60 primigravidae. In all groups there was an improvement in cervical status. This was significantly greater in those patients who received extra-amniotic prostaglandin gel and they also showed significant decreases in the mean induction-delivery interval and in the incidence of Caesarean section.     

Extra-amniotic Foley catheter and prostaglandin E(2) gel for cervical ripening at term gestation.

OBJECTIVE: This study evaluated the efficacy of intravaginal prostaglandin E(2) gel in comparison with that of a Foley catheter for cervical ripening and induction of labor. STUDY DESIGN: Consecutive patients with unfavorable cervix requiring preinduction cervical ripening and induction of labor at term gestation were asked to participate in the study. One hundred and two patients were assigned to treatment with intravaginal prostaglandin E(2) gel (group 1) and 122 patients underwent the placement of an intracervical Foley catheter (group 2). After a maximum of three applications of intravaginal prostaglandin E(2) gel (18h) or after 18h from Foley catheter insertion oxytocin was administered to patients not in active labor. Labor profiles and pregnancy and neonatal outcome were compared between groups. RESULTS: The groups were comparable in term of demographic characteristics, indications for induction of labor, Bishop score at admission. The induction to labor time and the induction to delivery time were similar between groups. The cesarean sections rate was higher in group 1 than in group 2 (26.5 versus 14.7%, P<0.05). This remained significant when the analysis was restricted to nulliparous patients (32.3 versus 14.2%). The incidence of urinary tract infections, chorioamnionitis, and febrile morbidity was similar between groups. CONCLUSION: For preinduction cervical ripening, the Foley catheter is a valid alternative to the application of intravaginal prostaglandin E(2) gel and it is associated with a lower cesarean rate in nulliparous women.     

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

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

Preinduction cervical ripening with sequential use of prostaglandin E2 gel

Two hundred patients received a prostaglandin E2-containing gel for preinduction cervical ripening. The gel was administered every 6 hours until a Bishop score greater than or equal to 7 was obtained or the attending physician deemed induction necessary. Forty-eight percent of the patients labored "spontaneously" after one or more gel applications. The average cumulative change in Bishop score with sequential application of the gel was 2.7. Sequential application of the prostaglandin gel proved no more effective in the process of preinduction cervical ripening than single application of the gel with a similar period of observation.     

A comparison of prostaglandin E2 gel and prostaglandin F2 alpha gel for preinduction cervical ripening

The unfavorable cervix remains a major obstacle to the successful induction of labor. Reported are results from an ongoing study of topical prostaglandin preparations used to effect preinduction cervical ripening. The current study compares the efficacy of 40 mg of prostaglandin (PG) F2 alpha versus 5 mg of PGE2, applied to the cervix in a methyltylose gel the night before attempted induction of labor. A prospective double-blind protocol was used similar to that which previously established the efficacy of the 5 mg of PGE2 preparation versus placebo at this institution. Results indicate the superiority of the PGE2 preparation as measured by change in Bishop score, Pitocin requirement, rate of cervical dilatation, and percentage of failed inductions. Cesarean section rates were similar in the two study groups, and no fetal or maternal morbidity was attributable to the preinduction ripening technique.     

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.     

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.     

Natural prostaglandins for induction of labor and preinduction cervical ripening

Prostaglandin (PG) E2 has superseded all other natural prostaglandins for induction of labor and pre-induction cervical ripening. This evolution and its rationale are briefly described. PGE2 has been administered intravenously, orally, vaginally, endocervically, and extra-amniotically for induction of labor. All of these, except the intravenous route, have also been explored for pre-induction cervical ripening. The distinction between formal induction and pre-induction is not always clearly made with many studies pursuing both goals at once. Nevertheless, the effectiveness of PGE2 to achieve ripening and induction is currently beyond doubt. In women with unfavorable induction prospects PGE2 results in lower rates of failed induction and higher rates of delivery within a reasonable interval than amniotomy and/or oxytocin. This also applies to women with prelabor rupture of the membranes, but the relative advantages of PGE2 over traditional methods are less clear for women with a favorable cervix. Vaginal administration of PGE2 has superseded virtually all other routes of PGE2 administration except the endocervical route, which tends to give variable results depending on spillage from the endocervical canal. Doses and formulations of vaginal PGE2 with various gels, tablets, pessaries and slow release inserts have varied widely and continue to do so. There is currently no evidence for the superiority of one PGE2 preparation over another.     

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

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

Factors predicting labour onset in patients treated with prostaglandin E2 for cervical ripening

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37–42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E₂ gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E₂ and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening.     

The effect of vaginal administration of various doses of prostaglandin E2 gel on cervical ripening and induction of labor

Eighty patients with a Bishop score of less than or equal to 4 were randomly administered vaginal triacetin gel containing placebo or prostaglandin E2 in 1, 2, and 3 mg doses. Twelve to sixteen hours later, those not in labor underwent oxytocin induction. Increasing doses of prostaglandin were effective in ripening the cervix, and the higher doses were associated with significant success in inducing labor.     

Prostaglandin E2-induced changes in the distribution of glycosaminoglycans in the isolated rat uterine cervix

In order to study the hormonal control mechanisms of cervical ripening, we investigated the prostaglandin E2 (PGE2)-induced changes in the distribution of glycosaminoglycans (GAG) using hysterectomized and ovariectomized rats, leaving the vascularized uterine cervix in situ, as an animal model. In the first series of experiments, the GAG were measured in a control (n = 22 Wistar rats) and in a PGE2-treated group (n = 20 Wistar rats) without steroid supplementation. In the second series of experiments, the GAG were measured in a control (n = 19) and in a PGE2-treated group (n = 18) receiving estradiol and progesterone supplements. After PGE2 treatment in the two series of experiments, and despite being surgically isolated from the uterine corpus, the cervix was still able to undergo some of the structural changes associated with normal ripening (increased hydration and hyaluronic acid concentration). This suggests that PGE2, acting directly on the cervix, could be, at least in part, a modulator of biochemical events which underlie normal cervical maturation. The animal model described here seems to be suitable for studying the hormonal mechanisms of cervical ripening and the regulatory relationship between cervical maturation and myometrial contractility, which are probably subject to concordant endocrine regulation.     

Cervical ripening. A retrospective experience with prostaglandin E2 "chips"

To improve the unfavorable cervix we instituted a policy of cervical ripening with "chips" of prostaglandin E2 suppositories. A standard, 20-mg suppository was cut into six equal parts, and one of the chips was inserted just inside the vaginal introitus every four to six hours. Repeat doses were utilized if no cervical change was evident and uterine activity was minimal. All the patients underwent continuous monitoring in the labor-and-delivery unit. Fifty patients with Bishop's scores of less than 4 underwent cervical ripening for a variety of obstetric indications. Forty-two patients (84%) achieved vaginal delivery. Three patients underwent cesarean delivery for fetal distress unrelated to hyperstimulation. Two additional patients experienced hyperstimulation; one of them required subcutaneous terbutaline. No other neonatal or maternal complications were encountered. Cervical ripening with prostaglandin chips may be a reasonable clinical alternative when one is faced with an obstetric indication for delivery in a patient with an unfavorable cervix.     

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.     

Intracervical Foley catheter balloon vs. prostaglandin in preinduction cervical ripening.

OBJECTIVES: The aim of this study is to compare the effectiveness of the intracervical Foley balloon catheter and 3 mg prostaglandin E(2) tablet(s) in preinduction cervical ripening. METHODS: Ninety women referred to the maternity clinic for induction of labor with a Bishop score of less than or equal to 5 were randomized to receive an intracervical Foley catheter or prostaglandin E(2) tablets. The primary measured outcome was ripening of the cervix as measured with the Bishop score. RESULTS: There were no differences in mean Bishop scores between the prostaglandin and the Foley catheter groups. Bishop scores (mean+/-S.D.) after ripening were 6.6+/-0.80 and 6.7+/-0.86 for the Foley catheter and prostaglandin groups, respectively (P=0.54). The Foley catheter group showed a statistically shorter time to ripening compared with the prostaglandin group (3.4+/-2.1 and 6.5+/-3.2 h, respectively (P=0.001). There was no statistically significant difference in induction time (4.8+/-1.8 h and 5.3+/-2.4 h, respectively (P=0.36). CONCLUSIONS: There are no differences in preinduction cervical ripening efficacy between prostaglandin E(2) and the Foley catheter, but the Foley catheter has the advantage of ripening an unfavorable cervix in a shorter time.     

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.     

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.     

Prostaglandin E2 gel for cervical ripening and induction of labor: a critical analysis

This report summarizes the cumulative experience of 3313 pregnancies represented in 59 prospective clinical trials in which intracervical or intravaginal prostaglandin E2 gel was used for cervical ripening before induction of labor. Results indicate that local prostaglandin E2 is superior to placebo or no therapy in enhancing cervical effacement and dilation, reducing initial induction failures, shortening the induction-delivery interval, reducing oxytocin use, and lowering the rate of cesarean section because of failure to progress. Certain advantages also exist for labor induction in the presence of a favorable cervical state. Uterine hyperstimulation or pathologic fetal heart rate patterns before oxytocin administration occur in less than 1% of reported cases and are usually dose related, self contained, and reversible with the use of beta-adrenergic tocolytic therapy. Maternal systemic effects in these low doses are negligible. Worldwide clinical experience has clearly demonstrated that prostaglandin E2 gel administered before induction of labor is of major therapeutic benefit and should become commercially available for more than investigational use.