Mid-trimester abortion induced by intravaginal administration of prostaglandin E2 suppositories.

Mid-trimester abortion was successfully induced in 70 of 71 patients by administration of vaginal PGE2 suppositories. The one patient who failed to abort with this method was pregnant in the blind horn of a duplex uterus. The mean abortion time for the successful inductions was 11.88 hours. Multiparous patients aborted somewhat faster than nulliparous patients, but the difference was not significant. Among the 70 successful inductions 42 patients aborted in 12 hours or less and only one patient had an abortion time of more than 24 hours. The drug appeared effective throughout the stages of gestation included in this series--from 8 to 27 weeks. Eight patients were monitored throughout the abortion procedure and uterine activity was calculated and analyzed. The development of uterine activity was gradual without the sudden rise in frequency of contractions and intrauterine baseline tonus that characterized prostaglandin administered by other methods. The most frequently encountered side effect of vaginal PGE2 suppositories was a temperature elevation, which returned to normal within a few hours of the last dose of the drug. Gastrointestinal disturbances--vomiting and diarrhea--were also common, despite a low initial dose of PGE2 and premedication with antiemetic and antidiarrheal agents. These side effects were in general well tolerated by the patients and never required termination of therapy. The cardiovascular effects of PGE2 in this series could be considered minimal. In a single patient surgical intervention was required to remove the placenta. In seven patients the placenta was removed by sponge forceps and in five patients the placenta was removed manually. There was an estimated blood loss exceeding 250 ml. in 10 patients, but transfusion was not required. Although white blood cell count rose significantly during the abortion period there were no significant changes in hematocrit or platelet count. Mid-trimester abortion with intravaginal administration of PGE2 suppositories appears to offer a valid alternative to the presently available techniques, with a rapid abortion time, high success rate, and low incidence of complications.     

Mid-trimester therapeutic abortion by intra-amniotic prostaglandin F2 alpha and concomitant oxytocin

The routine use of intra-amniotic PGF2 alpha and concomitant intravenous oxytocin for second trimester induced abortion is evaluated in 274 consecutive cases. Eighty-five per cent of the nullipara and 90 per cent of the parous women aborted within 24 hours and all but one within 48 hours following a single intra-amniotic dose. Doses were 40 or 50 mg PGF2 alpha and the mean induction-abortion interval was not shortened by the higher dose. Neither did gestational age have any effect on abortion time. Postabortum haemorrhage occurred in 22 cases in spite of routine curettage. Parametritis was reported in eight cases. In two nullipara, cervical tears were observed, in one case forming a persisting fistula to the uterine cavity. There were no significant toxic side effects to the administration of PGF2 alpha or oxytocin. It is concluded that the method has not been superseded with regard to efficacy of abortion induction and that the rate of more serious complications is not above what can be expected from any other available method of second trimester pregnancy termination.     

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.     

Management of intrauterine fetal demise and missed abortion using prostaglandin E2 vaginal suppositories.

Two hundred and twelve patients diagnosed as having a missed abortion or intrauterine fetal death were managed by the use of prostaglandin E2 vaginal suppositories. The method had a high efficacy rate with 98% of the patients experiencing successful evacuation of the uterine contents. The mean time to abortion was 10.9 hours with a mean dose of 60 mg (3 suppositories). Side effects were well tolerated. Transient pyrexia was present in 36% of the patients during therapy, but returned to pretreatment levels after abortion. No intrauterine infection was observed. The risks associated with active treatment can be avoided. The ease of administration permits initiation of therapy as soon as the diagnosis is confirmed.     

Cervical ripening with intravaginal prostaglandin E2 gel

Fifty-four patients were randomized in a double blind fashion into either a placebo group or a group treated with a 3 mg dose of an intravaginal prostaglandin E2 gel. The group receiving the prostaglandin E2 gel had a mean change in cervical score of 2.7 while the patients in the placebo group had no significant change. Even though a significantly higher number of patients in the prostaglandin group went into spontaneous labor, the incidence of cesarean section was not different between the two groups. Upon comparing the conflicting reports of various studies on the subject, it is concluded that the method of product preparation, particularly the source of prostaglandin E2 utilized and the choice of drug vehicle, may be important variables in determining treatment success, as measured in terms of decreased cesarean section rate.     

Cervical ripening with intravaginal prostaglandin E2 gel

Ripening of the cervix by intravaginal application of a prostaglandin-containing gel is evaluated. Thirty patients with an unfavorable cervix needing labor induction were studied in a double-blind, prospective fashion. The prostaglandin gel proved superior to placebo in ripening the cervix (P less than .05), reducing induction failures (P less than .025), diminishing the oxytocin dosage necessary for induction (P less than .05), and lowering the rate of cesarean section (.05 less than P less than .1). One hundred fifty additional patients with varying Bishop scores and differing clinical situations were also studied. There were 35 cesarean sections (23.3%), nine failed inductions (6%), a spontaneous labor rate of 46%, and an average Bishop score change of 2.5. Twenty patients with premature rupture of the membranes and an unfavorable cervix received a modified gel containing 2.5 mg of prostaglandin E2. Average Bishop score change was 2.9, and there was a 55% incidence of spontaneous labor.     

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.     

Preinduction cervical ripening with prostaglandin E2 intracervical gel

A double-blind, placebo-controlled, dose-ranging study was undertaken to evaluate the efficacy of two doses of intracervical prostaglandin E2 gel in patients with unfavorable Bishop scores. Mean change in Bishop score, success of softening, time to labor, and time to delivery were all significantly different in the two treatment groups as compared with the placebo group. Twenty-three of 30 treated patients had uterine contractions lasting greater than four hours and eight patients delivered during the observation period. Moreover, one case of uterine hyperactivity and five cases of severe fetal heart rate decelerations were noted in the treatment groups. Although efficacious for cervical ripening, caution is warranted when using this technique in patients at risk for placental insufficiency.     

Clinical utility of multiple-dose administration of prostaglandin E2 gel

An open-label study was undertaken to assess the clinical impact of multiple doses of intracervical prostaglandin E2 (0.5 mg) gel administered at 6-hour intervals. Fifty women with low Bishop scores requiring induction of labor were recruited. The prestudy mean Bishop score was 2.3 +/- 1.1 and changed significantly with one (p less than 0.001), two (p less than 0.001), and three (p less than 0.002) doses. The mean gestational age of patients receiving three doses was significantly less than that of patients receiving one dose, (38.5 versus 40.1 weeks, p less than 0.005). Prostaglandin E2 gel induced labor in 56% of patients, but 14% required subsequent oxytocin (Syntocinon) augmentation. Cesarean section was performed in 6% of patients. No deleterious fetal, neonatal, or maternal effects occurred.     

Plasma prostaglandin metabolite levels after use of prostaglandin E2 gel for cervical ripening

An ideal agent for cervical ripening should produce an increase in cervical scores without stimulating myometrial contractions. Currently used methods of preinduction ripening with prostaglandin E2 are frequently associated with contractions, limiting their use in high-risk patients. To discriminate between a direct effect of absorbed prostaglandin E2 and a triggering of the intrinsic mechanisms of labor, we measured circulating levels of stable metabolites of prostaglandin E2 and prostaglandin F2 alpha. Prostaglandin E2 gel insertion followed by a rise in prostaglandin E2 metabolite but not prostaglandin F2 alpha metabolite implies that contractions are secondary to absorbed prostaglandin E2.     

Routine induction of labour with extra-amniotic prostaglandin E2 in a viscous gel.

Prostaglandin E2, 350 microgram dispersed in a viscous gel, tylose, was introduced into the extra-amniotic space as a single dose in 285 patients to induce labour. With a favourable cervix, 82 per cent of multiparae and 50 per cent of primiparae were successfully induced. With unfavourable induction features, the success rates were 48 per cent and 24 per cent respectively. In the remaining patients, all but four were successfully delivered when intravenous oxytocin was also used. The method was safe, simple and inexpensive and had many advantages for patients and nursing staff.     

Preinduction cervical ripening with prostaglandin E2 (Prepidil) gel

The effect of preinduction cervical ripening with Prepidil, a commercially prepared prostaglandin E2 gel (0.5 mg), on the outcome of induction of labor with intravenous oxytocin was investigated. Fifty-nine pregnant women were randomized either to receive intracervical application of the gel or to undergo sham application. Compared to control subjects, patients in the group given Prepidil had significant increases in cervical Bishop scores, shorter induction-to-delivery intervals, lower maximum doses of oxytocin, and fewer days of induction. Systemic side effects were minimal, but 37% (11 of 30) of the gel-treated patients experienced labor prior to receiving oxytocin and 20% (six of 30) were actually delivered during the 12-hour ripening period. No differences in route of delivery or fetal outcome were found between the two groups.     

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.     

Increased decidual prostaglandin E concentration in human abortion

Prostaglandin E (PGE) concentration was measured in decidual tissue after spontaneous and missed abortion and compared with that obtained from induced abortion. Tissues were obtained by curettage from groups of 10 patients each and PGE was estimated by radioimmunoassay. After spontaneous and missed abortions decidual tissue contained significantly higher mean concentrations of PGE, (486.3 and 66.7 ng/g wet tissue respectively) than after induced abortion (18.6 ng PGE/g wet tissue). It is suggested that an increased rate of PGE biosynthesis or reduced breakdown, or both, may play a role in the mechanism of human abortion.     

Increased decidual prostaglandin E concentration in human abortion

Summary. Prostaglandin E (PGE) concentration was measured in decidual tissue after spontaneous and missed abortion and compared with that obtained from induced abortion. Tissues were obtained by curettage from groups of 10 patients each and PGE was estimated by radioimmunoassay. After spontaneous and missed abortions decidual tissue contained significantly higher mean concentrations of PGE, (486.3 and 66.7 ng/g wet tissue respectively) than after induced abortion (18.6 ng PGE/g wet tissue). It is suggested that an increased rate of PGE biosynthesis or reduced breakdown, or both, may play a role in the mechanism of human abortion.     

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.