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.     

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.     

Prostaglandin E2 gel versus misoprostol for cervical ripening in patients with premature rupture of membranes after 34 weeks

OBJECTIVE: To compare intravaginal misoprostol to prostaglandin (PG) E2 for cervical ripening in women with premature rupture of the membranes (PROM) after 34 weeks of gestation. METHODS :Women with PROM after 34 weeks of gestation and an unripe cervix were randomized to receive PGE2 (2.5 mg) or misoprostol (50 microg). Both agents were placed intravaginally immediately after randomization, and the dose was repeated 6 hours later if necessary. After another 6 hours from the second insertion, oxytocin treatment was started if labor had not begun. Forty patients in each group were required to show a 30% improvement in delivery within 12 hours in the misoprostol group. RESULTS: One hundred nine patients were randomized; 54 were assigned to misoprostol and 55 to PGE2. Important demographic and clinical characteristics were similar between the groups. The mean time from first insertion to delivery was 16.4 hours in the misoprostol group and 22.0 hours in the PGE2 group. A second dose was required less frequently in the misoprostol group (22% vs 62% in the PGE2 group), and the percentage of patients delivered within 12 hours was higher in the misoprostol group (41% vs 16%). Tachysystole occurred in 20% and 6% of women in the misoprostol and PGE2 groups, respectively. Hyperstimulation occurred in 9% and 0%, and cesarean delivery in 19% and 26% of women in the misoprostol and PGE2 groups, respectively. Neonatal outcome was similar between groups. CONCLUSION: Intravaginal misoprostol is more effective than local PGE2 application to treat PROM after 34 weeks of gestation, but tachysystole occurs more commonly with misoprostol.     

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.     

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.     

Influence of premature rupture of membranes on induction of labor and plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha and oxytocin levels in patients with unripe cervix

Rupture of membranes at term, whether spontaneous or artificial, causes rapid and sustained increase in prostaglandin F2 alpha (PGF2 alpha) metabolite (PGFM) levels and is associated with augmentation of uterine contractions. To investigate why premature rupture of membranes (PROM) often fails to initiate uterine contractions, we measured plasma concentrations of PGFM and oxytocin (OT) in patients with PROM near term. Serial blood samples were taken before and after PROM as well as before and after local PGE2 gel application for cervical ripening. For comparison, patients with similar criteria with intact membranes were also studied, as were patients in spontaneous labor at term with and without spontaneous rupture of membranes. PROM was always associated with an initial, marked increase in plasma PGFM. Whether or not this increased PGF2 alpha production was maintained was related to the cervical status at the time of PROM. In patients with unripe cervix PGFM levels returned to initial levels within 2 hours and no contractions were elicited; when the cervix was 3 cm or more dilated, PGFM levels remained high and contractions began within 1 to 3 hours. PROM had no significant effect on plasma OT levels. When PGE2 gel was applied to ripen the cervix, PGFM levels increased moderately within 30 minutes in all patients regardless of the status of the membranes. In patients with intact membranes the concentration of PGFM in plasma declined to initial levels within 4 hours, whereas in patients with PROM, PGFM levels remained increased throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of labor. A double-blind randomized controlled study of prostaglandin E2 vaginal suppositories compared with intranasal oxytocin and with sequential treatment

In a double-blind randomized controlled study of 300 women, 150 primiparas and 150 multiparas, induction of labor by means of vaginal suppositories containing 3 mg prostaglandin E2 (PGE2) was compared with the conventional method of intranasal oxytocin and with a combined method of 3 mg PGE2 vaginal suppositories alternating with intranasal oxytocin. In the PGE2 group the intensity of delivery was significantly greater than in the oxytocin group, among both primiparas and multiparas and among the patients with ripe and unripe cervix. The efficiency of the combined treatment could no be evaluated because of the high intensity of delivery during the first 24 hours. There were no maternal side effects, and no significant difference in the frequencies of failed induction and cesarean section.     

Role of prostaglandin in the management of prelabour rupture of the membranes at term.

OBJECTIVE: To compare conservative versus prostaglandin management of prelabour rupture of the membranes (PROM) in healthy primigravid women at term. DESIGN: A prospective randomized study. SETTING: Labour Ward, Aberdeen Maternity Hospital. SUBJECTS: 230 primigravidae at terms with PROM, 115 allocated to be treated conservatively and 115 to be managed with prostaglandin treatment. INTERVENTIONS: In the conservatively managed group the women were observed for up to 24 h after hospital admission with PROM. The actively managed group had PGE2 gel (2 mg) instilled into the posterior fornix and if contractions had not commenced, a further dose of PGE2 gel (1 mg) was instilled 6 h later. In both groups, if labour had not established 24 h after admission, intravenous oxytocin was given in escalating doses. MAIN OUTCOME MEASURES: PROM to delivery interval, oxytocin augmentation, mode of delivery, maternal and neonatal infective morbidity. RESULTS: There was a significant reduction in the PROM to delivery interval in the women managed actively with PGE2 gel and fewer women in the PGE2 group required oxytocin augmentation (31% vs 51%). The two managements groups were comparable for intrapartum analgesia, antibiotic treatment, babies requiring admission to the special care nursery unit and delivery by caesarean section. CONCLUSION: The early use of prostaglandin is associated with a significant reduction in PROM to delivery interval without a significant increase in infective morbidity or caesarean section rate. However, the advantages of the conservative approach should not be overlooked. More work is still needed in the management of those women where uterine activity fails to establish within 24 h after PROM.     

Cervical ripening with prostaglandin E1: how an ambulatory method decreases the hospital stay in abortus with intrauterine fetal demise

OBJECTIVE: This study was designed to determine whether use of prostaglandin E(1 )(PGE(1)) is justified to improve the known clinical outcome of prostaglandin E(2) (PGE(2)) gel, because PGE(2) gel preparations are more costly than PGE(1) tablets in most countries, and data to support the use of the gel in clinical practice is not conclusive. The aim was to compare the safety and efficacy of PGE(1) gel when applied in both an in-hospital or ambulatory setting to oxytocin infusion in those women with unfavorable cervical conditions prior to surgical abortion for either medical or obstetrical indications with intrauterine fetal demise. Surgical dilatation of the unripe cervix may result in cervical injury of uterine perforation which could prolong the hospital stay. METHODS: We used PGE(1) gel prepared from tablets and administered in the ambulatory form (group 1), the same PGE(1) gel administered in the labor room (group 2) and intravenously administered oxytocin in the labor room (group 3) for the induction of abortus in women complicated with intrauterine fetus death and missed abortion. Patients requesting abortion were eligible for inclusion, with >8 and <13 weeks of gestation. Eighty-nine women with unfavorable cervices (Bishop score 相似文献   

A comparative randomized study of oral prostaglandin E2 (PGE2) tablets and intravenous oxytocin in induction of labor in patients with premature rupture of membranes before 37 weeks of pregnancy

In a randomized prospective study, we compared the use of intravenous oxytocin with oral PGE2 tablets for stimulation of labor in cases of premature rupture of membranes (PROM) before term, where the onset of spontaneous labor did not occur within the first 3 h. This study represents the first of its kind in which oral PGE2 and oxytocin have been directly compared as oxytocic agents for PROM before 37 weeks. Labor induction was successful in 96% of patients in the PGE2 group compared with 84% in the oxytocin group. The incidence of cesarean section (CS) was 5% and 16% in the PGE2 and the oxytocin groups, respectively. While 10% of the CS were performed due to fetal bradycardia in the oxytocin group, none was performed in the PGE2 group despite the fact that the latter group had relatively lower Bishop scores. The data presented indicate that oral PGE2 is safe and effective in initiating active labor in healthy women at pre-term with PROM. Thus we recommend its use to induce labor 3 h after rupture of membranes before 37 weeks gestation.     

Prostaglandin E2 in tylose gel for cervical ripening before induction of labor

Two hundred seventeen women who received 3 mg of prostaglandin E2 (PGE2) gel applied to the cervix followed by adjunctive oxytocin were compared to 94 patients whose labor was induced with oxytocin alone (OA). Postdatism, pregnancy-induced hypertension and rupture of the membranes were the major indications for induction of labor, accounting for 70% of the PGE2 group and 88% of the OA group. Mean initial cervical scores were found to be significantly less favorable among PGE2 patients as compared with OA patients. Though PGE2 was associated with a significant improvement in mean cervical scores, responsiveness of the cervix to PGE2, as determined by clinical examination, was not necessary for a successful induction. Failed inductions were infrequent in both groups. Nulliparous PGE2 patients with unfavorable cervical scores had fewer cesarean sections (CSs) and shorter labors than did their OA counterparts. Complications were uncommon but largely due to the subsequent use of oxytocin. Patients with prior CSs were safely induced following PGE2 cervical ripening.     

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.     

Induction of labor by intra-cervical PGE2 in viscous gel. Mechanism of action and clinical treatment routines

Induction of labor in women with immature cervix was accomplished by four different treatment schedules. The case material included a total of 100 subjects, each treatment group having 25 cases: Group A: Intravenous oxytocin; Group B: Intracervical PGE2-gel followed by intravenous oxytocin; Group C: Intracervical PGE2-gel twice with a 12-hour interval; Group D: Intracervical placebo gel twice with 12-hour interval. Oxytocin did not influence the Bishop score (B.S.) unless in the presence of active labor contractions. In contrast, there was an increment in B.S. by 3.6 points on average within 12 hours following PGE2-gel as calculated from data of subjects without signs of contractions. These results support the concept of a local action of PGE2-gel. The increment in B.S. was larger in subjects with very immature cervices (B.S. less than or equal to 2) than in those with moderately immature scores (B.S. 4). A second PGE2-gel instillation did not increase the B.S. above the level achieved by the first application, indicating that pharmacological ripening of the cervix by a single dose of PGE2 results in an effect approaching maximum. The success rate was the same for oxytocin and PGE2-gel treated women during the first 24 hours, when approximately 40% of the women had given birth. The oxytocin group remained at that level of success rate, whereas the PGE2-gel-oxytocin and PGE2-gel X 2 series continued to improve their success rate up to 75%. An interesting finding in the study was that women given PGE2-gel twice did not need intravenous oxytocin stimulation except in a few cases.     

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.     

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.     

A comparison of oral prostaglandin E2 tablets with intravenous oxytocin for stimulation of labor after premature rupture of membranes at term

Sixty-nine patients (48 primigravidae and 21 multigravidae) with 12 hours of spontaneous premature rupture of membranes (PROM) after 36 weeks gestation were randomly allocated to receive either prostaglandin E2 (PGE2) oral tablets or intravenous oxytocin to stimulate labor. The two treatments were compared regarding stimulation - delivery interval (SDI), analgesic requirements, maternal and fetal side effects, and patient acceptability. The mean SDI was shorter in the oxytocin group, but without statistical significance. Analgesic requirements and fetal side effects were similar in the two groups, but there was a higher incidence of nausea and vomiting in those patients receiving the maximum dose (1 mg hourly) of PGE2. On subjective assessment, clinicians considered oxytocin to be more effective (p less than 0.05), while midwives felt both regimes to be equally helpful. PGE2 oral tablets were significantly (p less than 0.05) more acceptable to the patients, who preferred the convenience of oral dosing, the absence of an i.v. line and the increased mobility. It is concluded that PGE2 tablets are a safe and effective method of stimulating labor following PROM, and highly acceptable to parturients. In those women in whom labor has not been established within 8 h of initiating PGE2 therapy, or in whom gastric side effects are troublesome, intravenous oxytocin should be substituted.     

Induction of labor with oral misoprostol for premature rupture of membranes at term in women with unfavorable cervix: a randomized, double-blind, placebo-controlled trial

AIM: To evaluate the efficacy and safety of oral misoprostol for labor induction in women with term premature rupture of membranes (PROM) and an unfavorable cervix. METHODS: We randomized 130 women with PROM of < or =4 h to either oral misoprostol, 50 microg, or a placebo given every 4 h for up to three doses. Intravenous oxytocin was initiated if active labor did not begin within 12 h. RESULTS: Sixty-four women received oral misoprostol and 66 received placebo. The PROM-to-delivery interval was shorter with misoprostol than with placebo (13.7+/-5.8 vs. 20.3+/-6.8 h, respectively, P<0.05). Misoprostol significantly reduced the need for oxytocin (28.1 vs. 72.7%, P<0.001) and antibiotics (25 vs. 69.7%, P<0.001). No significant differences in cesarean section or hyperstimulation rate were noted. CONCLUSION: Oral misoprostol given to women with unfavorable cervix soon after term PROM significantly reduces the induction-to-delivery time and the need for oxytocin and antibiotics.     

Oxytocin and the initiation of human parturition. I. Prostaglandin release during induction of labor by oxytocin

Concentrations of plasma prostaglandins E and F and the 15-keto-13,14 dihydrometabolite of PGF2 alpha (PGFM) were determined by radioimmunoassay in 15 women who underwent induction of labor with oxytocin. Plasma PGFM rose significantly during the oxytocin infusion in nine women who went on to deliver vaginally but did not change in six women in whom induction of labor failed. Plasma PGE and PGF levels also rose during the infusion in the nine women with successful induction of labor but the changes were not statistically significant. In comparison to the six women in whom induction failed, however, plasma PGE in the nine women with successful induction reached significantly higher levels. Oxytocin infusions elicited uterine contractions of similar frequency in both groups of women, but the cervix failed to dilate in the six women in whom induction failed. The oxytocin-induced rise in plasma PGFM is, therefore, not simply a consequence of uterine contractions. We suggest that oxytocin stimulates PGF production in the pregnant uterus when it is appropriately sensitized to oxytocin, causing a potentiation of the oxytocin-induced contractions which is necessary for the contractions to become efficient in dilating the cervix. We further suggest that the stimulation of PGF production by oxytocin is mediated by oxytocin receptors, probably in the decidua.     

Prelabor rupture of membranes at term: induction techniques

The clinical management of premature rupture of membranes (PROM) at term has been a matter of considerable controversy. Management options have included expectant management or induction of labor with oxytocin, dinoprostone (PGE2), or misoprostol. Early studies suggested that immediate oxytocin induction of labor might reduce maternal and neonatal infections while increasing risk for cesarean section. The definitive TermPROM study found no difference in neonatal infections between immediate and delayed induction with oxytocin and PGE2. However, neither PGE2 nor delayed induction resulted in fewer cesarean sections than immediate oxytocin. Misoprostol offers several theoretical advantages over oxytocin in the setting of PROM at term. However, randomized trials to date have found no significant advantage for misoprostol administration compared with other agents for women with PROM.     

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.