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.     

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.     

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.     

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.     

Gemeprost for first trimester missed abortion

In 87 patients with a missed abortion prior to 13 weeks, the application of a prostaglandin (PG) E₁ derivative (1 mg gemeprost, Cergem®) was compared to conventional surgical termination of pregnancy by cervical dilatation and curettage. In 33 patients with PGE₁ application, complete expulsion of the abnormal pregnancy occurred after an average of 2.8 ± 1.5 vaginal suppositories. PGE₁ treatment was effective in 76.7%, and surgical management was effective in 90.9% of patients. Sixty percent of the patients in the PGE₁ group required analgesia because of uterine pain in comparison to 4.5% in the surgical group. The possibility of medical termination with synthetic PG derivatives should be further investigated.     

Interruption of pregnancy by prostaglandin 15-methyl F2alpha.

The current study was formulated to investigate the abortifacient activity of prostaglandin 15-methyl F2alpha (15-methyl PGF2alpha) administered intramuscularly to 80 healthy women with gestations between 8 and 22 weeks. Goals were the establishment of an effective dosage schedule and assessment of the incidence and severity of side effects. All 80 gravidas were aborted, with a mean time to abortion of 15.70 hours (SD, 6.52). Gastrointestinal side effects occurred in 89% of the patients; temperature elevations greater than or equal to 100.6 degrees F were noted in 14 cases. No other significant complications were encountered. Transabdominal intra-amniotic pressure monitoring indicated the need to administer the drug at 2-hour intervals. The 15-methyl PGF2alpha patients were matched for parity and gestational length with 80 gravidas aborted with PGE2 20-mg vaginal suppositories. The difference in interval to abortion in the two groups was not statistically significant. While gastrointestinal side effects were more common with 15-methyl PGF2alpha, the frequency of drug-induced temperature elevations was reduced.     

Cervical priming prior to dilatation and evacuation: A comparison of methods

Vaginal administration of prostaglandin analogues resulted in cervical changes that facilitated dilatation and evacuation in 80 patients in the late first trimester and the second trimester of pregnancy. When 0.5 mg and 1.0 mg of 15(S)-15-methyl-prostaglandin F_2α (15-ME-PGF_2α) was compared to 30 and 60 mg of 9-deoxo-16, 16-dimethyl-9 methylene prostaglandin E₂ (PGE₂ analogue), the PGE₂ analogue appeared to have more cervical ripening effect than did the 15-ME-PGF_2α. Overall, the 30 mg PGE₂ vaginal suppository seemed to offer the most optimal combination of effectiveness, sufficient cervical dilatation, and minimal side effects. With the prostaglandins, maximal cervical effect was observed at 4 to 5 hours; this rapid effectiveness allows administration of the prostaglandin to accommodate a 1-day stay for surgical evacuation. The preoperative cervical priming results with the prostaglandins were compared to those obtained with the use of laminaria tents. Although the number of patients who needed further dilatation at the time of operation was less with the laminaria, the incidence of complications and the time for adequate dilatation were higher in that group.     

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.     

Vaginal Misoprostol vs. Concentrated Oxytocin Plus Low-Dose Prostaglandin E2 for Second Trimester Pregnancy Termination

Objective: To examine the efficacy of vaginal misoprostol for mid-trimester pregnancy termination.

Results: Interim analysis of the first 30 (15-misoprostol, 15-concentrated oxytocin) women demonstrated that the 2 groups were similar with regard to indication for delivery, gestational age, and demographic characteristics. Misoprostol was associated with a lower success rate (67 vs. 87%, P =. 2), a longer induction-delivery interval (22 h vs. 18 h, P =. 09), a higher rate of retained placenta requiring curettage (27 vs. 13%, P =. 65), and a higher live birth rate (50 vs. 0%, P =. 006).

Conclusions: Compared to a regimen of concentrated oxytocin plus low-dose prostaglandin E₂, misoprostol administered as vaginal tablets in a dose of 200 μg q 12 h is not satisfactory for mid-trimester pregnancy termination in an unselected population.

Methods: This randomized trial compared misoprostol, 200 μg per vaginum q 12 h to a protocol of concentrated oxytocin plus low-dose vaginal prostaglandin E₂ suppositories (10 mg q 6 h). Success was defined as an induction-to-delivery interval ≤24 h.     

Vaginal misoprostol versus concentrated oxytocin and vaginal PGE2 for second-trimester labor induction

OBJECTIVE: To compare the efficacy, side effects, and complications of high-dose vaginal misoprostol with concentrated intravenous oxytocin plus low-dose vaginal prostaglandin (PGE(2)) for second-trimester labor induction. METHODS: One hundred twenty-six consenting women with maternal or fetal indications for pregnancy termination and no prior cesarean delivery were randomly assigned to receive either vaginal misoprostol 600 microg 1x, 400 microg every 4 hours 5x (misoprostol group, n = 60) or escalating-dose concentrated oxytocin infusions (277-1,667 mU/min) plus vaginal PGE(2) 10 mg every 6 hours 4x (oxytocin group, n = 66). Both groups received concurrent extra-amniotic saline infusion for cervical ripening. Women who failed their assigned regimen received 20 mg of PGE(2) suppositories every 4 hours until delivery. Analysis was by intent to treat. RESULTS: Demographic characteristics were similar between study groups. Median induction-to-delivery interval was significantly shorter in the misoprostol group (12 hours) than in the oxytocin group (17 hours; P <.001). There was a higher induction success rate at 24 hours in the misoprostol group (95%) than in the oxytocin group (85%; P =.06), although this difference did not reach statistical significance. The incidence of live birth (25% versus 17%), chorioamnionitis (5% versus 2%), and postpartum hemorrhage greater than 500 mL (3% versus 3%) were similar between the misoprostol and oxytocin groups, respectively. Diarrhea (2% versus 11%; P =.04), nausea/emesis (25% versus 42%; P =.04), and retained placenta requiring curettage (2% versus 15%; P =.008) were significantly less common in the misoprostol group when compared with the oxytocin group, respectively. Isolated intrapartum fever, however, was more frequent in the misoprostol group (67%) than in the oxytocin group (21%; P <.001). CONCLUSION: Compared with concentrated oxytocin plus low-dose vaginal PGE(2), high-dose vaginal misoprostol is associated with significantly shorter induction-to-delivery intervals, fewer side effects, a lower incidence of retained placenta, and comparable incidence of live birth.     

Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases

Objective To assess the effectiveness of a regimen comprising mifepristone followed by a combination of the vaginal and oral administration of misoprostol for mid-trimester medical termination of pregnancy.
Design Retrospective analysis of prospectively collected data in women undergoing mid-trimester medical termination of pregnancy.
Setting Aberdeen Royal Infirmary, Scotland.
Sample A consecutive series of 500 women with pregnancies of 13–21 weeks of amenorrhea undergoing legally induced abortion in one Scottish NHS hospital.
Methods Each woman received a single oral dose of mifepristone 200 mg and 36–48 h later vaginal misoprosto1800 pg. Three hours following the first dose of misoprostol, 400 yg doses were administered orally at three hourly intervals, to a maximum of four doses. Success was defined as abortion occurring with five doses of prostaglandin, or within 15 h of administration of the first dose of prostaglandin.
Results Ninety-seven percent aborted successfully. The median dose of misoprostol required was 1200 yg and the median induction-toabortion interval after first prostaglandin administration was 6.5 h. The median number of doses of misoprostol required to induce abortion, and the induction-toabortion interval, was statistically significantly higher among women at gestations 17–21 weeks than among those at 13–16 weeks ( P = 0–0001). A total of 9.4% required surgical evacuation of the uterus under general anaesthesia and 66.4% of the women were managed as day cases.
Conclusions The combination of oral mifepristone 200 mg followed by vaginally and orally administered misoprostol provides a noninvasive and effective regimen for second trimester termination of pregnancy.     

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.     

Prostaglandin E2 for induction of labor in patients with premature rupture of membranes at term.

OBJECTIVE: A prospective study comparing three management schemes for patients at term with premature rupture of membranes was performed. STUDY DESIGN: One hundred forty patients were randomized to one of three study groups: prostaglandin E2, placebo, or oxytocin. Patients randomized to prostaglandin E2 and placebo received vaginal suppositories containing 3 mg prostaglandin E2 or glycerin only, respectively; suppositories were administered in a double-blind fashion, on one or two occasions, 6 hours apart. Oxytocin was given only if labor was not established after 12 hours or to augment inadequate labor. In patients randomized to oxytocin labor was induced with intravenous oxytocin. The time interval to delivery, delivery outcome, and complications were analyzed. RESULTS: Patients receiving prostaglandin E2 were more likely to be in labor after one suppository and to be delivered without the addition of oxytocin when compared with placebo. The time interval to delivery was shorter with prostaglandin E2 and oxytocin induction versus placebo ("expectant management"). The incidence of maternal infection was lowest in patients with labor induced by prostaglandin E2. Although the overall cesarean section rate was low, there was a trend toward a lower rate with prostaglandin E2 induction. No adverse effects were observed with prostaglandin E2. CONCLUSION: Prostaglandin E2 can be used successfully to induce labor after premature rupture of membranes at term with greater ease of administration when compared with oxytocin.     

Repeated extra-amniotic administration of prostaglandin F2alpha for midtrimester abortion.

Midtrimester abortion was induced in 94 of 100 patients at 16 to 24 weeks' gestation by the extra-amniotic administration of 1170 microng of prostaglandin F2alpha (PGF2alpha) every 10 minutes. The number of prostaglandin doses varied from 16 to 24 depending on the patient's response to the prostaglandin. The median abortion time was 10.0 hours, and 82.0% of the patients aborted within 24 hours. Overall, 68.0% of the patients failed to expel the placenta within one hour of abortion of the fetus. Vomiting and diarrhea occurred among 42.0 and 17.0% of the patients, respectively. Compared with the intra-amniotic administration of a single 50 mg dose of PGF2alpha, the extra-amniotic procedure was associated with similar side effect rates, a higher rate of incomplete abortion, and a significantly shorter abortion time.     

Prostaglandin F2 alpha, oxytocin, and uterine activation in hypertonic saline-induced abortions

Intra-amniotic injections of hypertonic saline at midgestation induce uterine activity, which evolves into a laborlike pattern in less than 24 hours and is associated with progressive increase in uterine oxytocin response. This uterine activation occurred in the absence of a measurable increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). Only after 25 to 27 hours was a rise in plasma concentration of PGFM detected, which then increased in a parallel manner with cervical dilatation. By contrast, plasma oxytocin levels increased by almost 100% soon after the injection of hypertonic saline, declining to initial levels by 24 to 28 hours. Oxytocin infusion given after the intra-amniotic injection at rates resulting in about a fivefold increase in plasma oxytocin significantly accelerated cervical dilatation and the rise in plasma PGFM. Oxytocin infused before induction of abortion resulted in only a small and transient rise in plasma PGFM. Hypertonic saline injections thus increase the prostaglandin F2 alpha-stimulating action of oxytocin, which in turn may be responsible for the enhanced contractile response to the hormone. Myometrial activation after hypertonic saline injections is probably caused by an interaction of oxytocin and prostaglandin F2 alpha, and cervical dilatation depends on contractile activity and a critical increase in prostaglandin production.     

Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases.

OBJECTIVE: To assess the effectiveness of a regimen comprising mifepristone followed by a combination of the vaginal and oral administration of misoprostol for mid-trimester medical termination of pregnancy. DESIGN: Retrospective analysis of prospectively collected data in women undergoing mid-trimester medical termination of pregnancy. SETTING: Aberdeen Royal Infirmary, Scotland. SAMPLE: A consecutive series of 500 women with pregnancies of 13-21 weeks of amenorrhea undergoing legally induced abortion in one Scottish NHS hospital. METHODS: Each woman received a single oral dose of mifepristone 200 mg and 36-48 h later vaginal misoprostol 800 microg. Three hours following the first dose of misoprostol, 400 microg doses were administered orally at three hourly intervals, to a maximum of four doses. Success was defined as abortion occurring with five doses of prostaglandin, or within 15 h of administration of the first dose of prostaglandin. RESULTS: Ninety-seven percent aborted successfully. The median dose of misoprostol required was 1200 microg and the median induction-to-abortion interval after first prostaglandin administration was 6.5 h. The median number of doses of misoprostol required to induce abortion, and the induction-to-abortion interval, was statistically significantly higher among women at gestations 17-21 weeks than among those at 13-16 weeks (P = 0.0001). A total of 9.4% required surgical evacuation of the uterus under general anaesthesia and 66.4% of the women were managed as day cases. CONCLUSIONS: The combination of oral mifepristone 200 mg followed by vaginally and orally administered misoprostol provides a noninvasive and effective regimen for second trimester termination of pregnancy.     

The effects of intramuscular injections of 15(S)-15-methyl prostaglandin F2alpha in failed abortions

Intramuscular injections of 15(S)-15-methyl prostaglandin F2alpha (15-Me-PGF2alpha) induced abortion in 38 patients who had failed to abort with other techniques, such as intra-amniotic instillation of saline or PGF2alpha and intravaginal insertion of prostaglandin-impragnated Silastic devices. The intramuscular injections of 15-Me-PGF2alpha were initiated when the original abortion techniques, even when augmented by intravenous oxytocin, failed to produce expulsion of the fetus. The dose schedule was 250 microgram or 500 microgram every 2 to 4 hours, and the concomitant intravenous oxytocin was continued at a rate of 167 mU/minute. Of the 38 patients, 26 aborted with two or fewer injections of 15-Me-PGF2alpha, and 30 patients required only 1 mg of the drug to expel the fetus successfully. The mean time from the first injection of 15-Me-PGF2alpha to the expulsion of the fetus was 5.25 hours; one-half of the patients aborted in less than 4 hours. The placenta was expelled spontaneously in 15 patients, removed manually from the vagina in 18, and removed by sponge forceps in 3. Two abortions were incomplete and surgical intervention was required. Twenty-eight patients (74%) experienced gastrointestinal disturbances, chiefly vomiting and diarrhea. Intramuscular administration of 15-Me-PGF2alpha eliminates the need for repeated amniocentesis, and the dose may be adjusted to meet the precise requirements of the clinical situation.     

Vaginal prostaglandin E2 in the management of fetal intrauterine death.

The results of a multicentre clinical trial of prostaglandin E2 (PGE2) administered by the vaginal route in the management of intrauterine fetal death and missed abortion showed an overall efficacy of 97 per cent. The mean induction-abortion interval was 10.7 hours with a mean total dose of 60.4 mg of PGE2. Side effects were tolerated well and there was no evidence of significant alterations in hepatic or renal function.     

Pregnancy termination in the 2d and 3d trimester with prostaglandins depending on the cervix status

Termination of pregnancy was performed in a standardized, on the cervical state depending manner in 48 patients with abortion between the 16th and 27th week of gestation and in 20 women with intrauterine fetal death (IUFD) between the 28th and 41st week of gestation. At a Bishop-Score (B.S.) less than 7 cervical ripening was induced by intracervical application of 0.1 mg sulprostone gel. In patients with a very unripe cervix (B.S. less than or equal to 3) local applications of prostaglandin gel were repeated at 6 hours intervals until a B.S. greater than or equal to 5 had been achieved. For induction of labour 0.5 mg sulproston was injected intramuscularly after at least one sulproston gel application in a range between B.S. greater than or equal to 5 to 7. At a B.S. 7 intravenous infusion of oxytocin was administered, if necessary, for augmentation of labour. Most of the patients received epidural anaesthesia before induction of labour. The time interval between the beginning of the procedure and expulsion of the fetus ranged from 6.5 to 49.5 hours (mean = 26.3 h) in the abortion group and from 2.0 to 46.0 hours (mean = 20.0 h) in the IUFD group. The median interval between induction of labour and abortion/delivery was 4.3 hours (range: 0.5-27.0), and 5.5 hours (range: 0.7-9.3 h) respectively. No surgical interventions were necessary in any of the patients, and no cervical lesions occurred. Undesired systemic side effects to prostaglandins were observed in only 4 out of the 68 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin E2 suppositories as a second-trimester abortifacient

Despite the large number of second-trimester abortions performed each year in the United States through labor induction, the optimal method of inducing labor has not been developed. This study was performed to evaluate the efficacy and safety of vaginal prostaglandin E2 suppositories as an abortifacient. We analyzed the abortions at 14-24 menstrual weeks' gestation performed at Women's Hospital, Los Angeles, in 1985 and 1986. The abortion rate at 24 hours was 90.4%, with a mean induction-to-abortion time of 13.8 hours. Although gastrointestinal side effects were frequent, hemorrhage, infection and live births were infrequent. Prostaglandin E2 suppositories are a simple, effective and safe means of effecting second-trimester abortion that requires little surgical skill.