Gemeprost vaginal pessaries for inducing third-trimester intrauterine deaths

In 3rd trimester fetal death, when the cervix requires softening, labor may be induced by the administration of intravenous, intra-or extraamniotic, or vaginal prostaglandin E2 or intramuscular injections of synthetic prostaglandins, such as 15(S)-methyl prostaglandin F2 alpha. These methods all have various disadvantages. In 10 women with 3rd trimester intrauterine death, labor was induced by vaginal insertion of a 1 mg gemeprost (16,16-dimethyl-trans delta 2 prostaglandin E1 methyl ester) pessary. The mean number of pessaries s required was 1.9, and the mean duration of labor was 11.7 hours. The women remained mobile during most of the procedure. No patient required additional oxytocin, and the only side effects were mild fever and diarrhea.     

A comparison between vaginal prostaglandin E2 suppositories and intrauterine extra-amniotic prostaglandins in the management of fetal death in utero

This retrospective study was undertaken to compare the efficacy, side effects, and complications of prostaglandin E₂ (PGE₂) given as a vaginal suppository with those of PGE₂ administered via the intrauterine extra-amniotic route to induce labor after fetal death. The induction-to-delivery intervals were comparable, with 9.2 ± 3.94 hours and 8.6 ± 4.49 hours, respectively. However, the mean total amount of PGE₂ administered was much less via the intrauterine extra-amniotic route (1.8 milligrams) than by the vaginal suppository (45.2 mg). There was a 100% success rate in the patients treated by the intrauterine extra-amniotic route, but only a 91.3% success rate in those patients treated via the vaginal route. The side effects (vomiting, diarrhea, fever) and the complications (incomplete abortion, uterine rupture, oxytocin augmentation) occurred more frequently with the use of PGE₂ as a vaginal suppository. The vaginal route of administration of PGE₂ is somewhat more convenient, but the intrauterine extra-amniotic route may offer a higher degree of efficacy and safety with fewer side effects in the management of fetal death in utero.     

Control of prostaglandin induced uterine hyperactivity with intravenous ritodrine

The prostaglandins, F2 alpha and E2, are in extensive local use for the induction of labor. The main concern with oral and vaginal administration is the difficulty in controlling rapidly progressing labor and uterine hyperactivity. Herein we present a case where intravenous ritodrine was given as soon as hyperactivity and fetal heart rate decelerations were detected. With this treatment, the hyperactivity was controlled, fetal heart rate returned to normal and labor progressed normally to the birth of a healthy infant.     

Single Dose Extra-Amniotic Prostaglandin Gel for Midtrimester Termination of Pregnancy

Summary: The efficacy of a single dose of prostaglandin F2α gel instilled into the extra-amniotic space to induce termination of pregnancy in the second trimester has been assessed and compared with intra-amniotic prostaglandin F2α and with an extra-amniotic infusion of prostaglandin F2α combined with intravenous oxytocin. There was no significant difference between the methods in time taken to abortion, incidence of retained placenta, need for blood transfusion, or rate of sepsis. Single dose extra-amniotic prostaglandin gel is recommended as a safe, effective, and convenient method of midtrimester termination of pregnancy.     

Serum levels of oestradiol and progesterone during administration of prostaglandin F2alpha for induction of abortion and labour.

Prostaglandin F2alpha was used to induce abortion or labour in 84 women between the 11th and 44th weeks of pregnancy. Three different routes of administration were used, intravenous, extra-amniotic, and intra-amniotic. The extra-amniotic infusion of prostaglandin F2alpha produced a faster response than the other two routes. Less than one-third of the dose used in the intra-amniotic group was required in the extra-amniotic group for a complete evacuation of the uterus. Vomiting and diarrhoea occurred in 40% of the women in the intra- and extra-amniotic group, while the frequency was 88% in the intravenous group. Serum levels of progesterone and oestradiol decreased in accordance with the pattern found during spontaneous deliveries. The effect of prostaglandin F2alpha on the myometrium does not appear to be mediated via changes in the blood levels of progesterone or oestradiol.     

Second trimester pregnancy termination using extra-amniotic ethacridine lactate

OBJECTIVE--To investigate the efficacy of ethacridine lactate by the extra-amniotic route for second trimester pregnancy termination and its associated complications. DESIGN--Retrospective study of women undergoing second trimester termination, over 3 1/2 years, with extra-amniotic ethacridine alone, or extra-amniotic ethacridine supplemented later by extra-amniotic 15-methyl prostaglandin F2 alpha. SETTING--Teaching hospital in Bombay. PATIENTS--315 consecutive women undergoing late abortions with extra-amniotic ethacridine. Demographic features were similar in the two groups. INTERVENTIONS--In group 1, 207 women had 150 ml of 0.1% ethacridine lactate injected slowly into the extra-amniotic space. In group 2, 108 women had the initial injection supplemented 6 h later by an extra-amniotic injection of 250 micrograms (1 ml) of 15-methyl prostaglandin F2 alpha. MAIN OUTCOME MEASURES--The occurrence of abortion following the induction procedure. The development of complications such as haemorrhage, infection, or injury to the uterus or cervix. RESULTS--The method was successful in 191 women (92%) in group 1 and in 106 (98%) in group 2. The median induction-abortion intervals were 35 and 19 h, respectively (Mann-Whitney U test, P less than 0.001). The corrected complication rate was less than 10% (30 women), with unplanned uterine evacuation in 6% (20), haemorrhage in 1% (4), and pelvic infection in 4% (14). CONCLUSION--The use of extra-amniotic ethacridine lactate provides an effective and safe treatment method for second trimester legal abortion. The induction-abortion interval can be appreciably reduced by supplementary prostaglandin.     

Morbidity of dilatation and evacuation in the second trimester: an analysis

OBJECTIVE: To compare the rates of complications of dilatation and evacuation (D&E) in the second trimester of pregnancy. STUDY DESIGN: Retrospective analysis of early complications after D&E in the second trimester (group A: 1988-1994) in comparison with D&E in the first trimester (group B: 1997) and with the induction of abortion by extra-amniotic application of prostaglandins in the second trimester of pregnancy (literature). RESULTS: The overall complication rate of D&E was statistically significantly higher in the second than in the first trimester (p < 0.0001). The most frequent complication in both groups was a blood loss > 500 ml (p < 0.009). As with blood loss, there was a statistically significant increase in the incidence of postoperative bleeding (p < 0.001) and fever > 38 degrees C (p = 0.042) with rising gestational age, too. We registered similar rates for incomplete abortion, infection, cervical injury, uterine perforation and thrombosis. CONCLUSION: Second-trimester pregnancy termination with D&E is associated with higher morbidity rates than in the first trimester. Overall, the rates of complications of D&E in our study were acceptable and comparable with the results of previous studies. Compared with the induction of abortion by extra-amniotic prostaglandins, D&E shows lower morbidity rates. In particular, the advantages of D&E are in the early second trimester.     

Second trimester pregnancy termination with and without prostaglandins

The effectiveness of three methods for second trimester pregnancy termination [TOP) was compared. A retrospective analysis was made in 34 cases with TOP by intraamniotic saline instillation and 19 cases with extra-amniotic appreciation of y ballon-catheter, followed by stimulation of uterine contractions by intravenous oxytocin infusion. The results were compared with the ones in 13 prospectively studied cases in which the extra-amniotic appreciation of the ballon-catheter was preceded by treatment of the cervix with 0.5 mg prostin E2 intracervically. In nulliparous patients the treatment of the cervix with y single dose prostaglandins did not shorten the mean abortion time neither reduced the percentage of unsuccessful and prolonged abortions. In parous patients the abortion time was significantly reduced. No failed or prolonged abortions were registered.     

Extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening and induction of labor.

OBJECTIVE: To compare the effectiveness of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening, induction of labor and achievement of vaginal delivery in patients with unfavorable cervices. METHOD: A randomized trial of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha performed at Harare Central Hospital Maternity Unit, Zimbabwe. One hundred and sixty-four patients were recruited from those referred to Harare Central Hospital Maternity Unit who required induction of labor for either maternal or fetal indications. RESULTS: 162 patients (extra-amniotic PgF2alpha group, N = 81; extra-amniotic saline infusion group, N = 81) had complete information. Two patients (one from each group) were lost to follow up. The demographic characteristics of the patients and the indications for induction were not statistically different. There was a marginally statistically significant difference in the change of Bishop Score in favor of the extra-amniotic saline infusion (4.0, S.D. = 1.4) as compared to (4.5, S.D. = 1.5) for extra-amniotic PgF2alpha (P value = 0.047). All other parameters showed no statistically significant differences. Maternal and fetal complications were minimal and not significantly different. Extra-amniotic saline infusion was however almost six times cheaper than PgF2alpha. CONCLUSION: Extra-amniotic saline infusion is as effective as PgF2alpha, safe, but much cheaper than PgF2alpha and should be seriously considered as a method of first choice in resource-poor settings.     

Some clinical and theoretical aspects on prostaglandins in obstetrics and gynecology.

The present article discusses two aspects on prostaglandins, both related to the control of uterine contractility. One concerns a clinical problem, induction of abortion, and argues in favor of systemic instead of intrauterine administration of prostaglandins and the choice of E instead of F analogues. The other relates to the stimulatory effect on the myometrium of some recently detected endogenous prostaglandins. The discussion regarding the endogenous control of myometrial contractility has so far exclusively been focused upon the classical prostaglandins. It is, however, felt that substances like PGH2, PGI2 and thromboxane A2 may play a significant role in the regulation of uterine activity.     

Prostaglandins and therapeutic abortion

Clinical findings indicate that prostaglandins are potent oxytoics agents and that they may play a physiological role in labor and abortion. A number of clinical trials have demonstrated the successful induction of abortion in the 1st and 2nd trimesters of pregnancy using intravenous PGF2 alpha. A recent clinical trial by the authors using intravenous PGF2 alpha on 10 women 10-15 weeks pregnant resulted in 9 complete abortions and 1 incomplete abortion requiring surgical intervention. Induction-abortion interval ranged from 7 hours 55 minutes to 31 hours 39 minutes with a mean of 24 hours 41 minutes. Total amount of PGF2 alpha in the 9 successful cases had a mean value of 93.53 mg. There were side effects in all patients but no serious complications. A high incidence of side effects was observed at the 50 mcg/minute level; all regressed rapidly upon termination of infusion. The study suggests that PGF2 alpha is an effective abortifacient in both the 1st and 2nd trimesters. When compared with suction termination in the first trimester, prostaglandin use was more time consuming, more demanding of supervisory personnel, less successful, and thus more expensive. Further research must be done to determine how prostaglandins work, their efficacy, and optimum methods of administration and safety.     

Termination of second trimester pregnancy with single intra-amniotic and extra-amniotic instillation of prostaglandin F2 alpha and 15-methyl prostaglandin F2 alpha

The use of high doses of prostaglandin F2 Alpha and 15-Methyl prostaglandin F2 Alpha have proved highly successful in the termination of second trimester pregnancy. The present study evaluates experience obtained from using the recommended single dosage schedules and compares the relative effectiveness and safety of intra-amniotic and extra-amniotic routes. The success rates of intra-amniotic administration of PGF2 alpha and 15-methyl PGF2 alpha by transabdominal amniocentesis via polyethylene catheter threaded through an 18 gauge needle were 93.9% and 98% respectively. The number of incomplete abortions were also higher in the extra-amniotic group, being 80.2% with 15-me-F2 alpha as compared with 28.0% with intra-amniotic 15-me-F2 and 23.9% with intra-amniotic F2 alpha. This difference, however, is probably due to the fact that women in the intra-amniotic group had a completely formed placenta. The mean induction time was approximately the same for all groups and occurred within 24 hours. Parity had no significant correlation with the success rate, nor did the period of gestation (between 10 and 20 weeks). The latter factor had no correlation with complete or incomplete abortion, or the abortion induction interval. 18 cases out of the 20 studied failed to abort due to unresponsiveness of the uterus to the drug. The incidence of major side effects such as vomiting and diarrhea were comparable and clinically acceptable.     

Termination of first and second trimester pregnancy with intramuscular administration of sulproston,a new prostaglandin analogue

The efficacy and side effects of intramuscularly administered Sulproston, a new prostaglandin believed to have greater abortifacient potency and enhanced tissue selectivity, was evaluated in 40 women aged 16-42 admitted for legal abortion of 1st and 2nd trimester pregnancy. The gestation ranged between 7 and 12 weeks or 14 and 18 weeks, respectively. 1 mg of the prostaglandin analogue in 2 ml of 0.154 M saline solution was injected into the gluteal muscle every 6 hours with the treatment continued over 36 hours (6 doses) if needed. Following the intramuscular route the new prostaglandin analogue Sulproston failed to induce abortion in 1 of 40 patients, and the pregnancy was successfully terminated in this patient with an additional intravenous infusion of Sulproston beginning 12 hours following the intramuscular injection. 38 of the patients expelled the fetus in a mean induction to abortion time of 11.5 hours. There was complete abortion in 31 of the 40 patients. In all patients the uterus was evacuated following abortion to remove placental residues. 6 patients suffered uterine pain requiring analgesia; 1 patient had a transient pyrexia of 2 degrees C which subsided without antibiotics. Intramuscular administration of the new prostaglandin E2 analogue Sulproston has been found to be effective in inducing abortion. The incidence of local and systemic side effects is low compared with that after natural prostaglandins.     

Changes in the synthesis and metabolism of prostaglandins by human fetal membranes and decidua at labor

The production of prostaglandins by dispersed cells from human amnion, chorion, and decidua was examined at term before the onset of labor and at spontaneous vaginal delivery. In order to obtain detailed information about relative prostaglandin production rates, the time course of prostaglandin output was examined by incubating the cells for up to 4 hours and measuring the cumulative output of prostaglandin E2, prostaglandin F2 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha in the incubation media. The output of all three prostaglandins was low in tissues obtained before the onset of labor. At labor there was an increased production of prostaglandins E2 and F2 alpha in amnion and a small increase in the output of prostaglandin E2, prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha in decidua. In contrast, chorionic cells obtained at spontaneous vaginal delivery showed high levels of 13,14-dihydro-15-keto-prostaglandin F2 alpha in the media with no net production of prostaglandin E2 or F2 alpha. These data suggest a high rate of specific in vitro prostaglandin synthesis in amnion and decidua at labor, accompanied by a high rate of prostaglandin metabolism in chorion.     

The use of prostaglandins for the induction of labor

This paper attempts to assess the present status of the use of prostaglandins (PGs) in induction of labor. According to the published literature over 1000 patients have been treated with intravenous administration of PGF2alpha, a method which seems to be at least as effective as oxytocin infusion. Some authors suggest that this mode of action may be more effective in patients with lower Bishop scores at start of infusion. Intravenous infusion of PGE2alpha has been found to be 10 times more potent than PGF2alpha, regardless of mode of administration; success rates and amount of side effects are similar. Oral administration of PGE2alpha has shown to be as effective as oxytocin in 786 elective inductions of labor; the oral way of administration is more effective in the latent and early active phase of labor. 15 methyl PGE, a chemically modified PG, is as effective as its parent compound, has the same side effects, can be used in smaller amounts, but does not have any major advantages over the natural compound. In general it takes less than 1/10 the dose of PG to initiate labor than it takes to induce abortion, and the side effects are reduced about the same degree; since PGs may cause hypertonus care should be taken in monitoring the fetal condition and in controlling the rate of PG administration. Considerable work is needed before the full value of PGs in induction of labor can be assessed.     

A comparison of vaginally administered misoprostol with extra-amniotic saline solution infusion for cervical ripening and labor induction

OBJECTIVE: The purpose of this study was to compare intravaginal misoprostol with extra-amniotic saline solution infusion with concomitant oxytocin for cervical ripening and labor induction in viable pregnancies. STUDY DESIGN: Two hundred women with indications for labor induction and unfavorable cervices were assigned randomly to vaginal misoprostol or extra-amniotic saline solution infusion. Twenty-five micrograms of misoprostol was administered every 4 hours up to six doses, followed by intravenous oxytocin administration. Patients who had received extra-amniotic saline solution infusion also received intravenous oxytocin along with a maximum 12-hour saline solution infusion through Foley catheters that were placed above the internal cervical os. RESULTS: One hundred women were randomly assigned to misoprostol, and 100 women were assigned randomly to extra-amniotic saline solution infusion. The average interval from start of induction to vaginal delivery was longer in the misoprostol group (1323.3 +/- 700.3 minutes) than in the extra-amniotic saline solution infusion group (970.4 +/- 502.7 minutes; P =.006, log transformed data). Abnormal fetal heart rate tracings were found in 30% of the patients who received misoprostol and in 19% of the patients who received extra-amniotic saline solution infusion (relative risk, 1.6; 95% CI, 1.0-2.4; P =.05). There was more tachysystole in the misoprostol group (8%) than in the extra-amniotic saline solution infusion group (1%; P =.02). There were no differences in the routes of deliveries or neonatal outcomes between groups. CONCLUSION: Extra-amniotic saline solution infusion with oxytocin administration appears more effective and is associated with fewer maternal complications than misoprostol for cervical ripening and labor induction.     

Studies on platelet function during different modes of administration of PgF2alpha in obstetrics and gynecology

Platelet function has been studied during intravenous, intraamniotic, and extraamniotic administration of prostaglandin F2alpha (PgF2alpha) for termination of missed abortion and missed labor, for therapeutic abortion, and for induction of term labor. The controls received oxytocin i.v. (missed labor and term labor). Our investigations have shown that there was a normalization of the increased spontaneous platelet aggregation and a significant reduction of ADP- and collagen-induced platelet aggregation in the groups given PgF2alpha i.v. The desaggregation in these groups was increased. The other groups given PgF2alpha showed no significant changes in platelet function. Inducing labor by oxytocin we found a tendency to increased platelet aggregation and decreased desaggregation. The clinical importance of these findings and the consequences for hemostasis are discussed.     

Continuous extraovular administration of prostaglandin F2alpha for midtrimester abortion

Midtrimester abortion was successfully induced in 74 of 76 patients by a continuous extraovular administration of (PGF2alpha) prostaglandin F2alpha via a constant-infusion pump. 2 patients in the 13th-14th weeks of gestation failed to abort despite good uterine activity. The mean abortion time for successful inductions was 16.21 hours. Parous patients aborted somewhat faster than nulliparous patients, but the difference was not statistically significant. All patients were monitored throughout the abortion procedure, and uterine activity was calculated and analyzed. Uterine activity developed within 15 minutes of PGF2alpha instillation and showed the characteristic uterine response to PGs with a sharp rise in intrauterine tonus. The gastrointestinal side effects in this series were much less than those reported for intraamniotic instillation of PG, and there was good patient tolerance of the procedure. The main complication of extraovular administration of PGF2alpha for midtrimester abortion was endometritis, which occurred in 7 patients. The patients who developed endometritis had, as a group, longer abortion times (mean=28 hours). 3 patients with severe preeclampsia and intrauterine death in the third trimester also had successfully induced labor with extraovular administration of PGF2alpha. The method of PGF2alpha administration in the series was found to have a high success rate, good patient tolerance, and fewer side effects than when abortion was induced by intraamniotic instillation of PGF2alpha.     

Prostaglandin induction of midtrimester abortions: three years' experience of 626 cases

In the first part of the survey 424 midtrimester abortion inductions with 11 different regimes of treatment were analyzed according to PG dose, PG type (PGF2alpha or PGE2), the route of administration (intravenous, extra-amniotic, and intra-amniotic), and the dose of concomitant intravenous oxytocin. Intraamniotic PG was given as a single injection, and the dose was repeated after 24 hours, if the abortion was not imminent. The highest efficacy, a 90% success rate within 24 hours and a 100% rate in 48 hours, as well as the shortest induction-abortion interval were achieved with the intra-amniotic administration of 50 mg of PGF2alpha either alone or with supplementary oxytocin, or with the intra-amniotic 10 mg PGE2 plus oxytocin.