Mid-second-trimester labor induction: concentrated oxytocin compared with prostaglandin E2 vaginal suppositories

A concentrated oxytocin infusion and prostaglandin E2 (PGE2) vaginal suppositories were compared in a retrospective analysis for indicated abortion in the mid-second trimester (17-24 weeks' gestation). Eighty-one women underwent second-trimester pregnancy termination, 59 by PGE2 suppositories and 22 by concentrated oxytocin infusion. Success was achieved by PGE2 in 93% (55 of 59) and oxytocin in 91% (20 of 22). The mean duration of labor was 13.1 hours with PGE2 and 8.2 hours with oxytocin. The mean dose of PGE2 was 65.2 mg; of oxytocin, 200 units. Women who received PGE2 experienced nausea (46%), vomiting (37%), fever (64%), and diarrhea (20%) despite appropriate premedication. Few side effects occurred in the women who were treated with oxytocin. We conclude that concentrated oxytocin infusion seems to be a reasonable alternative to PGE2 vaginal suppositories for induction of labor in the mid-second trimester.     

Biosynthesis of prostaglandins (PGs) and effect of PGs on C-AMP content in the rabbit uterine cervical tissue at term

The effects of prostaglandins (PGs: PGE2, PGI2 and PGF2 alpha) on contractility, PGs production by A-23187 and C-AMP production by these PGs were studied in the rabbit uterine cervical tissue at term in vitro. PGE2 or PGI2 had an inhibitory effect on the contractility; the inhibitory effect of PGE2 was more potent than that of PGI2. On the other hand, PGF2 alpha had an excitatory effect on the contractility. The mean rate of 6-keto-PGF1alpha production by A-23187 was more remarkable than those of PGE2 and PGF2 alpha. The PGE2 production was the second highest among the three PGs. The C-AMP was significantly increased by PGE2 and PGI2. The increased C-AMP level induced by PGE2 was greater than that by PGI2. On the other hand, PGF2 alpha did not increase C-AMP. From these experimental results, it seems that the production of large amounts of PGE2 and PGI2 facilitates cervical dilatation during parturition, and suggests that C-AMP participates in the cervical dilatation elicited by both PGE2 and PGI2.     

Labour Induction with Low Dose PGE2 Vaginal Gel: Result of an Australian Multicentre Randomized Trial*

An open-label, parallel, randomized study was conducted in 6 Australian hospitals involving 320 women near term who required induction of labour. Labour induction with 1 or 2mg of PGE2 in a vaginal triacetin gel repeated if necessary at 6 hours was compared to induction by amniotomy and intravenous oxytocin. Analysis of the 2 groups confirmed matching with regards demographic and clinical data. A significantly longer and more variable mean induction to onset of established labour interval was recorded in the PGE2 group (6.7 +/- 4.8 versus 2.0 +/- 1.1 hours. (p less than 0.001). The mean period of established labour was also longer (8.1 versus 6.0 hours, p less than 0.001) in the PGE2 group. However, 48% of PGE2 treated patients versus 29% oxytocin treated patients (p less than 0.01) were recorded as not experiencing strong contractions. Twelve hours after induction 65% of the PGE2 group and 93% of the oxytocin group were in established labour; 24% of the PGE2 treated group required subsequent augmentation with oxytocin. Spontaneous delivery occurred in 69% of PGE2 treated women and 62% of those treated with oxytocin (N.S.). Analgesic requirements were not statistically different between the groups. Fewer fetal heart rate abnormalities were recorded in the PGE2 treated group (p less than 0.02). No serious and only minimal adverse events were recorded in either treatment group.     

Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study

Forty primigravid women due to undergo first trimester termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E2 in gel or gel only as placebo. In the PGE2-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of 11.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE2-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15%) patients, fetal demise was observed. The mean induction-abortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE2-gel group. Termination of pregnancy was found to be easier in the PGE2-gel group, compared to the placebo group.     

Intracervical application of prostaglandin gel for induction of term labor

A new gel for local application of prostaglandins has been elaborated. The new gel, based on a lyophilized prostaglandin E2 (PGE2) starch powder, seems to have solved most of the pharmaceutical and clinical problems associated with local administration of prostaglandins. In a randomized double-blind study, 50 nulliparous patients with an unfavorable cervical state at term were given 2 ml gel containing 0.5 mg PGE2 (PGE2 gel) or gel without PGE2 (placebo gel). The gel was deposited into the cervical canal. Among patients given PGE2 gel, 11 of 25 had induced labor, delivering without further stimulation within 24 hours. In patients given placebo gel, 2 of 25 were delivered with 24 hours. This difference is statistically significant (P less than .01). Patients undelivered after treatment with PGE2 gel achieved a considerable and statistically significant improvement of cervical score, whereas in patients in whom labor was not induced successfully by placebo gel treatment no significant changes in cervical score were registered. In a subsequent open study another 70 term patients of varied parity were given 0.5 mg PGE2 gel. Thirty-eight patients (54%) had successfully induced labor. Among the remaining undelivered patients, considerable ripening of the cervix occurred. Thus, the cervical score changed from a mean of 3.2 prior to treatment to a mean of 6.5 by 24 hours after treatment. Gastrointestinal discomforts were not observed. Signs of uterine hyperstimulation were registered in 1 patient.     

Urinary PGE2 levels in toxemia of pregnancy

Urinary PGE2 levels in urine collected over 24 hours were measured by radioimmunoassay after chloroform extraction. In normal pregnancy, urinary PGE2 levels did not change during pregnancy. After 36 gestational weeks, urinary PGE2 levels in severe hypertensive pregnancy (616 +/- 91 ng/day (mean +/- S.E., n = 18)) were significantly decreased compared to those of normal pregnancy (1,039 +/- 85 ng/day, n = 13, p less than 0.005) and mild hypertensive pregnancy (1,025 +/- 140 ng/day, n = 8, p less than 0.03). We then analyzed the urinary PGE2 levels by noting clinical symptoms and their severity. Urinary PGE2 levels in the severe blood pressure group were significantly decreased compared to those of the mild group. There was a significant negative correlation between urinary PGE2 and mean blood pressure, systolic pressure and diastolic pressure. Diastolic pressure in particular had the most significant negative correlation with the urinary PGE2 level (n = 33, r = -0.593, p less than 0.001). Urinary PGE2 levels in the severe proteinuria and edema groups were significantly decreased compared to those in the mild group. These results suggested that renal synthesis of PGE2 may be decreased in severe hypertensive pregnancy and closely related to blood pressure, especially to diastolic pressure, and also related to the occurrence of edema.     

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.     

Follicular fluid cyclic nucleotides, prostaglandin E2, leukotriene B4, oestradiol, progesterone and luteinizing hormone in women stimulated by clomiphene and gonadotropins

The concentrations of cyclic AMP, cyclic GMP, prostaglandin E2 (PGE2), leukotriene B4 (LTB4) oestradiol, progesterone and luteinizing hormone (LH) were determined in 30 follicular fluid samples from 25 women in an IVF programme. Multiple follicular development was induced by clomiphene citrate and human menopausal gonadotropin. Laparoscopic aspiration of follicular fluid was performed 36 hours after injection of human chorionic gonadotropin. The mean concentration of LH was significantly lower (p less than 0.05) in the follicular fluid with ova developing to embryos that cleaved than in those without cleavage. The mean concentrations of cAMP, cGMP, PGE2, LTB4, oestradiol and progesterone were not significantly different. PGE2 and LH concentrations in the follicular fluids showed significant correlation (r = 0.56; p = 0.004). Significant correlation was also seen between cAMP and progesterone concentrations (r = 0.50; p = 0.006). The presence of cyclic nucleotides, PGE2 and LTB4 in human follicular fluid suggests that these factors may have a role in the function of the follicular fluid.     

Hygroscopic cervical dilators and prostaglandin E2 gel for preinduction cervical ripening. A randomized, prospective comparison.

A randomized, prospective study compared the safety and efficacy of hygroscopic cervical dilators (36 patients) with intracervical prostaglandin E2 (PGE2) gel (38 patients) in preinduction cervical ripening. Maternal age, gestational age and parity were similar in both groups. Both groups had similar cervical Bishop scores upon admission. The change in the cervical score was 3.0 +/- 0.3 (mean +/- SEM) in the dilator group and 2.8 +/- 0.4 in the PGE2 group (P = .7). The mean length of time from amniotomy to delivery was similar in both groups (10.1 +/- 1.0 and 10.3 +/- 1.3 hours, respectively) (P = .9). The proportions of patients in each arm of the study undergoing cesarean section were similar. Eight cesarean sections (21.0%) were performed in the PGE2 group; seven (19.4%) were performed in the dilator group (P = .9). Maternal morbidity, five-minute Apgar scores and admissions to the neonatal intensive care unit were similar in the two groups. Because patients were required to stay in the labor-and-delivery unit for four to six hours of fetal monitoring after PGE2 application, the costs were higher in that group. The dilators and PGE2 gel appear comparable in efficacy as preinduction cervical ripening agents. The need to monitor patients receiving PGE2 gel, however, appears to favor the choice of the dilators from a cost and convenience perspective.     

Induction of labor in patients with missed abortion and fetal death in utero with protaglandin E2 suppositories

Labor was successfully induced in 20 patients with a diagnosis of missed abortion or intrauterine fetal death (IUFD) by intravaginal administration of prostaglandin E2 suppositories. Fifteen patients delivered with the prostaglandin alone while a concomitant oxytocin infusion was employed to augment contractions in the other five patients. The mean induction-delivery time was 9.80 hours; nulliparous patients delivered in a mean time if 7.78 hours, parous patients in a mean time of 12.29 hours. The uterus appeared to be sensitive to the PGE2 stimulation in all patients and all were delivered completely without the need for surgical intervention. Fifty per cent of patients were delivered within 8 hours and 80 per cent by 12 hours. The side effects associated with prostaglandin administration--vomiting, diarrhea, and temperature elevation--were well tolerated and therapy did not have to be terminated in any patient. The administration of PGE2 vaginal suppositories offers an effective and safe technique for the induction of labor in patients with IUFD. Labor can be induced with PGE2 suppositories as soon as the diagnosis of IUFD is confirmed, which eliminates the need for waiting until spontaneous labor occurs.     

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.     

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.     

Use of prostaglandin E2 for cervical ripening in pregnancies with oligohydramnios

The effectiveness of intracervical prostaglandin E2 (PGE2) was studied in 96 primigravidas with unfavorable cervix and need for induction of labor. Group A consisted of 49 oligohydramnios and group B of 47 cases with normal amniotic fluid volume (controls). A single dose of 0.5 mg PGE2 gel was applied intracervically and several parameters were recorded during the next hours. The mean number of uterine contractions increased during the first 2 h in both groups, decreased during the next one and did not change significantly afterwards. The mean fetal heart rate (FHR) in group A decreased during the first 2 h and then increased, staying always within normal limits. The mean FHR in group B increased for 2 h, decreased during the next hour and did not change significantly afterwards. No significant differences were found between the two groups regarding mode of delivery, Apgar score and neonatal acidosis. Intracervical PGE2 appeared to effectively stimulate cervical ripening and labor induction in oligohydramnios, without causing side effects to the uterus and fetus.     

Chorioamnionitis and ontogeny of circulating prostaglandin and thromboxane in preterm infants

Our objective was to determine the effect of chorioamnionitis on plasma prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) during the first week in preterm infants. Plasma PGE2 and TxB2 were measured at 1, 3, and 7 days of age in preterm infants (birth weights 501 to 1500 g), with ( N = 26) and without ( N = 22) chorioamnionitis. Infants with maternal chorioamnionitis had significantly lower mean gestational age ( P = 0.0001) and birth weight ( P = 0.03) and a marginally higher rate of bronchopulmonary dysplasia (37% versus 12.5, P = 0.05), a result that may be related to the lower mean gestational age. Plasma PGE2 and TxB2 varied widely, more so on the first day but did not significantly differ between the two groups. TxB2 was lower among infants who died or developed morbidities. Circulating PGE2 and TxB2 concentrations in preterm infants in the first week vary considerably, are relatively unaltered by chorioamnionitis, and are lower in association with mortality and clinical morbidities. Further research on their role in the causation of adverse neonatal outcomes is necessary.     

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.     

Oral prostaglandin E2 for induction of labor

PGE2 (prostaglandin E2) had been successfully used in initiating labor in term pregnancies (Karim and Sharma, 1971). This study evaluates the safety and efficacy of prostaglandin for induction of labor in 23 patients (gestational length, 38-41 weeks; mean age, 27; age range, 17 to 40; parity 0 to 6). 20 received an oral PGE2 0.5 mg tablet hourly while 3 received an initial dose of 0.5 mg with 0.5 mg incremental increase hourly. 20 patients delivered vaginally liveborn infants without neonatal depression according to Apgar score and subsequent behavior in the nursery. 2 patients delivered by C-section and 1 was excluded from the study because of inadequate duration of treatment. Mean time to delivery was 5 hours, 47 minutes; mean drug dose, 2.53 mg. Mild transient emesis and diarrhea occurred in 2 patients, and emesis only in 1. Bishop induction score did not correlate with total dose of PGE2 used. Parity correlated negatively with dose necessary to achieve delivery (p0.05). The findings confirm the efficacy and safety of oral PGE, which provides an alternate drug and route for induction of labor. Oxytocin induction is briefly compared with prostaglandin induction.     

The use of antiprogestin (RU 486) for termination of second trimester pregnancy

Pretreatment with laminaria tent is often used in prostaglandin-induced second-trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects.     

Preinduction cervical priming with PGE2 intracervical gel

A prospective, randomized, controlled clinical trial was conducted to evaluate the safety and efficacy of a single, 0.5-mg dose of prostaglandin E2 gel in a shelf-stable triacetin base administered intracervically in patients with an unfavorable cervix (Bishop score less than or equal to 4) 12 hours prior to oxytocin-induction of labor. forty-eight evaluable patients were enrolled, 25 in the PGE2 group and 23 in the control group. PGE2 gel treatment resulted in a significant improvement in the mean Bishop score compared to control (3.14 versus 0.70, P less than .00005). Sixty-four percent of the patients treated with PGE2 had regular uterine contractions during the 12-hour preinduction period beginning 2.18 +/- 2.0 hours after gel insertion, compared to 9% in the control group, P = .0001. Moreover, 12% (3/25) of the patients receiving PGE2 progressed into active labor and delivered during the preinduction period. The duration of oxytocin infusion required for the induction or augmentation of labor was significantly shorter for patients who received intracervical PGE2 gel compared to the control group (13.1 +/- 8.1 versus 19.0 +/- 8.7, P less than .05). However, there was no significant difference in the incidence of cesarean section between the two study groups (40 and 22% in the PGE2 and control groups, respectively). No episodes of uterine hypertonus or hyperstimulation or gastrointestinal side effects occurred as a result of PGE2 gel treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrauterine pressures in labours induced by amniotomy and oxytocin or vaginal prostaglandin gel compared with spontaneous labour

Uterine activity during the first stage of labour was measured by an intrauterine transducer in 22 women induced with intravaginal PGE2 gel, in 37 induced by amniotomy and intravenous oxytocin, and in nine women in spontaneous labour. The nulliparous women in the PGE2 gel group had a significantly longer pre-established phase of labour and a significantly shorter established phase than nulliparae induced by amniotomy and oxytocin. The mean levels of total uterine activity (kPas) during labour and the uterine activity integrals (kPas/15 min) were significantly lower in nulliparae induced with PGE2 gel than in those induced by amniotomy and oxytocin. These findings suggest that PGE2 gel has a positive, beneficial effect on cervical compliance during the pre-established phase, resulting in less myometrial effort during established labour. These effects were less evident in parous women, probably because of an innate lower cervical resistance due to their previous labours. Uterine activity patterns during the 4 h leading to full cervical dilatation in nulliparae were similar in labours induced with PGE2 gel and spontaneous labours, whereas labours induced by amniotomy and oxytocin exhibited a significantly different pattern. Expulsion of the fetus during normal labour is a function of both uterine contractions and a decrease in the cervical resistance and the data suggest that induction by PGE2 gel more closely mimics spontaneous labour, whereas the predominant effect of oxytocin is to stimulate myometrial activity.     

Intrauterine pressures in labours induced by amniotomy and oxytocin or vaginal prostaglandin gel compared with spontaneous labour

Summary. Uterine activity during the first stage of labour was measured by an intrauterine transducer in 22 women induced with intravaginal PGE2 gel, in 37 induced by amniotomy and intravenous oxytocin, and in nine women in spontaneous labour. The nulliparous women in the PGE2 gel group had a significantly longer pre-established phase of labour and a significantly shorter established phase than nulliparae induced by amniotomy and oxytocin. The mean levels of total uterine activity (kPas) during labour and the uterine activity integrals (kPas/15 min) were significantly lower in nulliparae induced with PGE2 gel than in those induced by amniotomy and oxytocin. These findings suggest that PGE2 gel has a positive, beneficial effect on cervical compliance during the pre-established phase, resulting in less myometrial effort during established labour. These effects were less evident in parous women, probably because of an innate lower cervical resistance due to their previous labours. Uterine activity patterns during the 4 h leading to full cervical dilatation in nulliparae were similar in labours induced with PGE2 gel and spontaneous labours, whereas labours induced by amniotomy and oxytocin exhibited a significantly different pattern. Expulsion of the fetus during normal labour is a function of both uterine contractions and a decrease in the cervical resistance and the data suggest that induction by PGE2 gel more closely mimics spontaneous labour, whereas the predominant effect of oxytocin is to stimulate myometrial activity.