Early pregnancy termination with mifepristone and misoprostol in the United States

BACKGROUND: Mifepristone and a prostaglandin have been used successfully to terminate pregnancy in Europe and China. We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks' duration. METHODS: We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers. The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment. RESULTS: Two thousand fifteen women completed the final assessment. Among them, pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92 percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395 of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent. Failures, defined as cases requiring surgical intervention for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increased with increasing duration of pregnancy. The largest increase was in failures representing ongoing pregnancy, which increased from 1 percent in the < or =49-days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain, nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing gestational age. Two percent of the women in the < or =49-days group, as compared with 4 percent in each of the other two groups, were hospitalized, underwent surgical interventions, and received intravenous fluids (P=0.008). CONCLUSIONS: This mifepristone-misoprostol regimen is effective in terminating pregnancies, especially in women with pregnancies of 49 days' duration or less.     

Pregnancy interruption by vaginal misoprostol

A total of 132 pregnant women with average gestational age of 14.2 weeks (range 11-22 weeks) undergoing legal abortion volunteered for a trial utilizing vaginal administration of misoprostol. In 106 women a dose of 800 micrograms was utilized, whilst in 26 women 1,200-1,600 micrograms were given. Nonsurgical expulsion of the fetus was successful in 117 cases (88.6%). Four cases had to be excluded for various social reasons. A total of 11 did not achieve fetal expulsion within 56 h after application of misoprostol. These cases (11/132; 8.3%) were considered failures. Previous reports in the literature of toxicity trials on animals reporting no fetotoxic nor teratogenic effects of misoprostol at doses up to 10,000 micrograms/kg body weight seem to be of no validity in the human since we could demonstrate that almost 80% of pregnancies were interrupted at a dose of 10-15 micrograms/kg body weight. The conclusion is that vaginal administration of this prostaglandin analogue, not requiring cool temperature for storage, is remarkably effective in achieving safe interruption of pregnancy without any significant complications.     

Trends since 1989, in France, of induced abortions by mifepristone (RU486) combined with a prostaglandin analogue

In 1989 the French Ministry of Health gave its agreement to the utilisation of the combination mifepristone + a prostaglandin analogue for abortion up to 49 DA. Since then, research activities have been carried out to improve this method. Research to define the best prostaglandin analogue: sulprostone and gemeprost were dropped out; misoprostol was authorized in 1992 following very convincing trials, it is now commonly used and has never generated any major problem. Research to extend the application time limit to 63 DA: it showed a significant drop in efficiency (86.8% instead of 95.4%) as well as an increase of the rate of haemorrhages (2.25% instead of 0.3%). Therefore the method currently used reads as follows. Day 1: mifepristone 600 mg, day 3: misoprostol 400 micrograms, day 10-15: control visit. The efficiency rate is 95.4%; an additional dose of 400 micrograms of misoprostol 3 hours after the first dose if no expulsion has occurred, increases the rate up to 98.5%. This method is well accepted by women as it enables an early abortion and avoids surgery and anesthies. The arrangements required to implement the method are not easy to make as they call for a change of habits by the institutions as well as by medical teams. CONCLUSION: Since the use of misoprostol, the abortion by mifepristone using. 400 micrograms + 400 micrograms of misoprostol has become a method which is safe, efficient and much appreciated by women, but it implies a change in the usual practice of abortion.     

Efficacy of methotrexate and misoprostol for early abortion

BACKGROUND: Medical termination of pregnancy (medical abortion) as an alternative to surgical abortion has many advantages since it does not require anesthetics and there is no risk of cervical laceration or uterine perforation. In the present study, we evaluated the efficacy of methotrexate and intravaginally administered misoprostol for early abortion. METHODS: The study population consisted of 32 women seeking abortion of a normal intrauterine pregnancy of 8 weeks or less documented by ultrasound. The dose of methotrexate was 50 mg/m2 intramuscularly and the dose of misoprostol was 800 micrograms intravaginally. The final outcome of treatment was evaluated on day 14 or 16, and an abortion was considered successful if pregnancy was terminated without a surgical procedure. RESULTS: Abortion occurred in only 23 (71.8%) of 32 women. There were 9 failures (28.1%); 3 were ongoing pregnancies (9.3%) and 6 were incomplete abortions (18.7%) requiring suction curettage. After the exclusion of treatment failures, the mean duration of vaginal bleeding was 16.3 +/- 2 days. No serious side effects occurred as a result of methotrexate and misoprostol treatment. CONCLUSION: The use of methotrexate and intravaginal misoprostol for the termination of pregnancy requires larger studies to determine the safety and efficacy of this medical abortion, a comparison with RU 486 in prospective controlled randomized trials is necessary.     

A study on the optimal regimen of mifepristone with prostaglandin for termination of early pregnancy

One thousand and thirty-five women in early pregnancy (< or = 49 days), who requested medical abortion were randomly allocated into 8 groups. Mifepristone and 15-methyt-PGF2 alpha vaginal suppository (PG05) and misoprostol oral (tablets) were given as the following 8 regimens: group 1 (n = 195): a single dose of mifepristone 200 mg + PG05 1 mg on the 3rd or 4th day; group 2 (n = 249): mifepristone 25 mg b.i.d. (total amount of 150mg) + PG05 1mg on the 3rd or 4th day; group 3 (n = 67): mifepristone 25 mg b.i.d. (total amount of 125mg) + PG05 1mg in the morning of the 3rd day; group 4 (n = 108): a single dose of mifepristone 200mg + misoprostol 600 micrograms on the 3rd day; group 5 (n = 199): a single dose of mifepristone 150mg + misoprostol 600 micrograms on the 3rd day; group 6 (n = 60): mifepristone 50 mg was given immediately, then 25 mg b.i.d. (total amount of 150mg + misoprostol 600 micrograms; group 7 (n = 123): mifepristone 50 mg in the morning and 25mg in the evening for two days (total amount of 150 mg) + misoprostol 600 micrograms; group 8 (n = 34): mifepristone 25 mg b.i.d. (total amount of 125mg) + misoprostol 400 micrograms. As a result, the complete abortion rate of each group was 92.8%, 95.2%, 92.5%, 93.5%, 87.4%, 98.4%, 92.7% and 94.1% successively. The rate of group 5 was significantly lower than that of group 2 and 6 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Methotrexate and misoprostol to terminate early pregnancy

BACKGROUND: Although medical termination of pregnancy is available in Europe and China as an alternative to surgical termination, political and social factors have blocked medical approaches to pregnancy termination in the United States. Methotrexate, which is toxic to trophoblastic tissue, has been used safely to treat unruptured ectopic pregnancies. This report describes the use of a single low dose of methotrexate followed by intravaginal misoprostol for the medical termination of early pregnancy. METHODS: Women seeking termination of pregnancy were selected for this study on the basis of their good general health, emotional stability, and a pregnancy of 63 days or less in duration. Each woman received an intramuscular dose of methotrexate (50 mg per square meter of body-surface area). Five to seven days later, 800 micrograms of misoprostol was administered intravaginally. If abortion did not occur after seven days, the women was offered a second dose of misoprostol or vacuum aspiration. Successful abortion was defined as a complete termination of pregnancy within seven days after the first or second administration of misoprostol. RESULTS: A total of 171 of the 178 women enrolled in the study (96 percent) had successful medical abortions. Twenty-five women (14 percent) did not have an abortion after the first dose of misoprostol and received a second dose. Eighteen subsequently had complete abortions, but seven required suction curettage. In all seven women who required suction curettage, there was histologic evidence of disruption in the conceptus. No important side effects or complications were noted. CONCLUSIONS: The combination of methotrexate and misoprostol represents a safe and effective alternative to invasive methods for the termination of early pregnancy.     

Visceral varicella-zoster after bone marrow transplantation: report of a case series and review of the literature

OBJECTIVE: To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. METHODS: One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). RESULTS: Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. CONCLUSION: Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.     

Early abortion. Update and implications for midwifery practice

Medical abortion using methotrexate and misoprostol and manual vacuum aspiration are two new methods for pregnancy termination during the first 8 weeks of gestation. Compared to the regimen of mifepristone (RU 486) and misoprostol, both methods offer high rates of complete abortion and acceptability to users. Limitations of the new two-drug regimen compared with mifepristone include a longer time to effect abortion, transient gastrointestinal side effects, and risk of potential teratogenicity from methotrexate's cytotoxicity. Compared to standard surgical abortion, both methods allow women to avoid surgery, are more privately performed, and may be more easily accessible. The safety of first-trimester abortion provided by nurse practitioners and physician assistants has been established. Whether midwives and either new method to their practices depends on several factors. These include obtaining appropriate training, overcoming legal restrictions, and meeting professional and personal challenges inherent in providing early abortion care.     

A comparison of intravaginal misoprostol and intracervical prostaglandin E2 gel for ripening of unfavorable cervix and labor induction

OBJECTIVE: To study the effectiveness of single application of intravaginal misoprostol versus intracervical prostaglandin E2 gel for ripening the unfavorable cervix and labor induction. METHOD: One hundred and ten patients with indications for induction of labor with unfavorable cervices were randomized to receive either 100 microgram tablets of misoprostol placed in the posterior vaginal fornix or prostaglandin E2 1.5 mg in gel placed into the endocervix. Those, who were not in active labor after 24 hours, had labor induced with amniotomy and oxytocin. RESULTS: Among 110 patients recruited, 60 received misoprostol and 50 received prostaglandin E2 gel. The average interval from start of induction to vaginal delivery was 19.14 +/- 10.64 hours in misoprostol group and 21.37 +/- 13.09 hours in the prostaglandin E2 group (p = 0.33). Five patients (8%) in the misoprostol group had induction of labor after 24 hours of the treatment compared with 13 patients (26%) in the PGE2 group. The difference was significant (p = 0.03). Oxytocin augmentation was 35% in the misoprostol group and 34% in the prostaglandin E2 group (p = 0.86). There were no significant differences between routes of delivery. Nineteen patients (31%) in misoprostol group and 16 patients (32%) in the PGE2 gel group had cesarean deliveries. There was one case (1.7%) of uterine hyperstimulation in the misoprostol group and none in the PGE2 gel group. There were no significant difference in Apgar scores < 7 at 1 and 5 minutes, or admission to the neonatal intensive care unit between the 2 groups. CONCLUSION: Vaginal misoprostol is an effective agent for cervical ripening and induction of labor. Complications associated with prostaglandin administration were not statistically different between the 2 groups, but hyperstimulation occurred more in misoprostol group.     

Determination of DMPC hydration in the L(alpha) and L(beta'') phases by 2H solid state NMR of D2O

OBJECTIVE: To compare the effect of vaginal misoprostol with that of placebo when used prior to dilation and aspiration in women with a missed abortion. METHOD: Eighty-four pregnant women with a missed abortion were randomized to receive either vaginal misoprostol (200 micrograms) or placebo the day before the planned dilatation and aspiration under inhalation anesthesia. RESULT: Thirty-five women (83.33%) in the misoprostol group and 6 women (17.14%) in the placebo group aborted spontaneously prior to the scheduled dilatation and aspiration, P < 0.0001. The mean insertion to spontaneous expulsion time was 11.63 +/- 6.14 h in the misoprostol group compared to 11.95 +/- 5.43 h in placebo. In the misoprostol group two women required intramuscular pethidine for analgesia. In the placebo group there were two cases of blood loss in excess of 500 ml and one woman with a uterine perforation. CONCLUSION: Vaginal administration of misoprostol to women with a missed abortion produced spontaneous expulsion of the pregnancy and reduced the need for surgical treatment.     

A randomized trial of 2 regimens for the administration of vaginal prostaglandins (gemeprost) for the induction of midtrimester abortion

The most frequently used method for second trimester termination of pregnancy is administration of gemeprost (16, 16-dimethyl-trans delta 2-prostaglandin E1methyl ester) as a vaginal pessary. This provides a safe and effective method for achieving abortion. The current prescribing advice is to insert the pessaries into the posterior vaginal fornix every 3 hours. This study compares this to a 6-hourly regimen. The median abortion interval in the 6-hour group was shorter than the 3-hour group (15 versus 16 hours respectively) but the cumulative abortion rates were similar (98% in the 3-hour group and 91.8% in the 6-hour group). The 6-hour group required a significantly lower total dose of gemeprost to induce abortion. There was no difference in the rates of side-effects in the 2 groups but those receiving pessaries every 6 hours required less analgesia. This study finds no advantage in giving gemeprost every 3 hours.     

Young people with spina bifida: transfer from paediatric to adult health care

INTRODUCTION: The method used to terminate pregnancy on medical grounds during the second trimester must be safe, rapid, psychologically feasible and associated with a minimal risk of long-term sequelae. The objective of the present work was a critical analysis of the author's standard protocol of termination of pregnancy during the second trimester. MATERIAL AND METHODS: For induction of abortion during the second trimester the authors used a synthetic prostaglandin analogue (PG) F2 alpha-Dinoprost which was administered in a single dose of 30 mg by the intraamniotic route. At the time of onset of uterine contractions the authors administered peridural anaesthesia. The authors investigated indications, mean period of induction, correlation between the period of induction of abortion and the indications for termination of pregnancy, the week of pregnancy and parity of the mother. They recorded also the type and number of complications. RESULTS: From January 1991 till June 1997 179 pregnancies were terminated by intraamniotic PG administration. After a single intraamniotic PG administration 72% women aborted within 24 hours. In 26% women the intraamniotic administration was repeated twice and in 2% women three times. The mean induction period, i.e. the interval between the administration and abortion of the foetus was 22.6 hours. The interval was significantly longer (28 hours) in foetuses where pregnancy was terminated because of a neural tube defect (p < 0.01). The authors did not detect a correlation between the period of induction and the indication, week of gestation and parity of the mother. COMPLICATIONS: once a general reaction to intraamniotic administration, in three patients a major blood loss replaced by transfusion of erythrocyte mass, no uterine rupture. CONCLUSION: In all instances the therapeutic effect was achieved and there was no need to perform section minor. The disadvantage of the method is the high price of the preparation and need of repeated intraamniotic administration of PG in 29% of the patients.     

Sequence analysis of the terminal protein precursor coding regions from bovine adenovirus serotypes 2 and 3

The acceptability of medical abortion (mifepristone and misoprostol) among US women was investigated in a 1995 survey of 262 women seeking this method of pregnancy termination at 3 clinics in Oregon, Washington, and Vermont. The abortion patients' mean age was 27 years; mean gestational age was 49.5 days. 51.1% of respondents had experienced at least one prior abortion. Women completed a questionnaire at their initial clinic visit and again two weeks after the procedure. Participants chose medical abortion to avoid surgery (62.8%) or because they perceived it to be less invasive (56.3%), more natural (40.5%), and associated with a lesser risk of infection or damage to the uterus (35.1%) than vacuum aspiration, and could be performed earlier in pregnancy (27.2%). 49.8% indicated they preferred to wait for abortion to occur with a partner, friend, or family member, while 30.6% preferred to be alone; only 17.6% wanted to wait with other women undergoing the same procedure. Comparison of pre- and post-abortion questionnaires indicated women expected significantly more discomfort than they actually experienced and underestimated the number of days of bleeding. 72.8% of respondents were very satisfied with their medical abortion and 15.5% were somewhat satisfied. Women in the somewhat satisfied group had experienced significantly more abortion-related discomfort and anxiety than those who were very satisfied. Prior abortion experience and demographic characteristics did not influence satisfaction. 94% stated they would recommend medical abortion to a friend and 87% would select medical abortion if they had to terminate another pregnancy. Medical abortion has the potential to increase access to abortion among underserved groups of US women. Appropriate educational materials should be developed to help women choose between abortion methods.     

Analysis of 369 abortions conducted by mifepristone (RU486) associated with sulprostone in a French family planning center

OBJECTIVE: To investigate the use of oral mifepristone (RU486; Roussel-Uclaf, Paris, France) associated with IM injection of sulprostone (Schering, Lys-Lez-Lannoy, France) for the induction of legal abortion (7 weeks of amenorrhea in France). DESIGN: An uncontrolled observational study. SETTING: A public family planning center in Paris. PATIENTS: Three hundred sixty-nine (369) pregnant women with up to 7 weeks amenorrhea undergoing legal abortion. INTERVENTIONS: Six hundred milligrams (600 mg) of oral mifepristone followed 48 hours later by an IM injection of 250 micrograms of sulprostone. MAIN OUTCOME MEASURES: Frequency of complete abortion and the need for subsequent surgical evacuation, hospitalization, and blood transfusion. Measurement of the beta-hCG concentration before and 14 days after the oral administration of mifepristone. RESULTS: There was complete abortion in 93.2% of the cases. Of the 25 failures, 8 were continued pregnancies, 6 terminated pregnancy but without expulsion of the conceptus, and 11 were placenta retentions. Eight women required short hospitalization, but none needed blood transfusion. Among the 25 failures, 23 had a beta-hCG concentration > 500 IU/mL [sensitivity 92%, specificity 83%]. CONCLUSION: The sequential use of oral mifepristone and IM injection of sulprostone is effective in inducing abortion up to 7 weeks of amenorrhea. Nevertheless the risk of maternal morbidity associated with sulprostone and also the risk of fetal malformations in cases of continued pregnancy indicate that this method should only be used in specialist centers.     

Histological study of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins

OBJECTIVE: To study the histological changes of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins (PG). METHODS: A total of 24 women who requested medical abortion was recruited. For each woman, 3 cervical biopsies were taken: before mifepristone treatment; 48 hours after mifepristone 150 mg single dose treatment (i.e. immediately before PG administration); and 1 hour after gestational sac expulsion. Specimens were studied by optical and electron microscopy. RESULTS: Significant collagenolysis as demonstrated by marked reduction and irregularity of collagen fibers, abundant accumulation of an amorphorous material of ground substance, and infiltration of neutrophilic polymorphonuclear leukocytes were shown in stroma as well as in the deep portion of cervix after mifepristone as compared to the samples of early pregnant cervix before treatment. These changes presented to a further extent after the expulsion of gestational sac. CONCLUSION: The changes observed were similar to previous reports during cervical dilatation in term delivery. The present study confirmed the histological cervical ripening effect by mifepristone and suggested it may be used as cervical ripening agent before induction of labor as well.     

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from S?o Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.     

Effects of luteal phase administration of mifepristone (RU486) and prostaglandin analogue or inhibitor on endometrium in the rhesus monkey

Early luteal phase administration of a potent anti-progestin like mifepristone (RU486) inhibits blastocyst implantation and the establishment of pregnancy without marked changes in menstrual cyclicity and ovarian steroid hormone profiles; however, the underlying mechanism is not very clear. In the present study, a hypothesis that prostaglandins (PG) are involved in the anti-gestatory action of luteal phase mifepristone was tested. Endometrial changes in rhesus monkeys were examined following luteal phase administration of mifepristone, a prostaglandin synthesis inhibitor (diclofenac) and a prostaglandin analogue (misoprostol) either alone or in combination. Twenty-five monkeys were randomly assigned to six groups: group 1 (n = 4), normal control group; group 2 (n = 4), mifepristone (2 mg, daily, s.c.) treated group; group 3 (n = 4), diclofenac (25 mg, daily, i.m.) treated group; group 4 (n = 4), misoprostol (100 microg, daily, oral) treated group; group 5 (n = 5), mifepristone and diclofenac (same dosages as for groups 2 and 3) treated group; group 6 (n = 4), mifepristone and misoprostol (same dosages as for groups 2 and 4) treated group. All treatments were given to monkeys on days 16-18 of mated cycles and endometrial tissue samples were collected on day 20. With diclofenac alone (group 3), marginal changes were observed in glandular, stromal and vascular compartments, and there were few apoptotic bodies in gland cells; partial inhibition and delay in implantation was earlier reported. Significantly higher oestrogen receptor expression in glandular epithelial cells as compared with all other treatment groups was found after treatment with misoprostol alone (group 4) and was associated with normal fecundity. The anti-nidatory action of luteal phase antiprogestin treatment alone or in combination with diclofenac or misoprostol was associated with altered endometrial histometric features characterized by glandular apoptosis, regression in secretory functions, decreased oedema, extravasation and a higher degree of stromal leukocytic infiltration. In these three groups (groups 2, 5 and 6) receptors for oestrogen and progesterone receptors were significantly higher in stromal cells, and lower in vascular cells, while glandular cells showed significantly higher progesterone receptors compared with the control group. The anti-nidatory activity of mifepristone and associated endometrial changes could not be accentuated or attenuated with co-administration of PGE or diclofenac, nor could these be mimicked by these agents alone.     

Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy

BACKGROUND: Vaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient. METHODS: 66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy. FINDINGS: More women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial. INTERPRETATION: Pretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.     

Gameprost, sulproston and dinoproston for induced abortion in the 15th-24th week of pregnancy

In a randomized, prospective study at the Dept. of Obstetrics and Gynecology of the University Hospital of Giessen 4 different ways of inducing abortions with prostaglandins were tested between the 15th and 24th week of gestation. The aim of the study was to determine the best approach to inducing abortion in order to minimize the psychological and physical stress to the patient. Subjects randomized to the first two groups got a single cervical installation of either 0.5 mg Dinoprostongel (Prepidil, N = 22) or 0.5 mg Sulprostongel (Nalador, N = 21). Six hours later, i.v. infusion with Sulproston (8.3 micrograms/min) was started and continued until the abortion was complete. Patients randomized to the third and fourth group received either 0.5 mg Dinoprostongel intracervically (N = 15) or 1 mg Gemeprost vaginal suppositories (Cergem, N = 21) every 6 hours until the cervix was 1-2 cm dilated. Subsequently the patients received an i.v. infusion with Sulproston until the abortion was complete. In the first group with intracervical application of Sulproston the total time until abortion was 17.8 h +/- 7.8 h. This was shorter than following a single application of Dinoprostongel (22.5 h +/- 14.7 h). Although there was a five hours difference, the between-group differences were not statistically different because of a wide range in values following Dinoproston treatment. This range could not be explained by the age of the mother, week of gestation or parity. In the group receiving multiple intracervical applications of Dinoproston the time till expulsion was twice as long as that after multiple vaginal suppositories of Gemeprost (33.8 h +/- 13.9 h vs. 15.6 +/- 6.0 h, p < 0.01). The time span until a cervical dilatation of 1-2 cm was 27.0 h +/- 13.7 h in the group with repeated Dinoproston application. This period of time was more than twice the time span seen in the group with repeated Gemeprost application (12.5 h +/- 4.2 h, p < 0.01). On the average four treatments with intracervical Dinoprostongel were required while the average with Gemeprost vaginal suppositories was two to achieve a cervical dilatation of 1-2 cm. Furthermore in 7 of 21 cases treatment with Gemeprost achieved the expulsion of the fetus without Sulproston infusion (11.4 h +/- 5.2 h). Comparing single versus repetitive prostaglandin application we could demonstrate that the duration of Sulproston infusion was cut in half after repeated therapy with Gemeprost. We conclude that repetitive application of Gemeprost vaginal suppositories decreases the time to abortion and subject discomfort tremendously. The application of Gemeprost suppositories provides the easiest and most efficient therapeutic approach for both patients and staff. Furthermore the regiment that provided the best results was also the most cost-effective (range 180,-DM to 317,- DM per case).