Second Dose Of Misoprostol Research Articles

Traitement médical des fausses couches spontanées précoces: Étude prospective d’une prise en charge ambulatoire à l’aide du misoprostol

Medical treatment using misoprostol has been recommended as an alternative to surgical evacuation for spontaneous miscarriages in the first trimester, in order to avoid anesthesia, a surgical operation and hospitalization. Our aim was to assess the efficacy and the safety of vaginal misoprostol in out-patient management of early miscarriages. We conducted a prospective cohort study including patients with a spontaneous miscarriage of less than 14 weeks gestation. Exclusion criteria were hemorrhagic miscarriages, gestational sac larger than 40 mm and/or cranio-caudal length of the embryo of more than 30 mm. Our protocol used 4 intravaginal tablets (800 microg) of misoprostol on Day 1, out-patient follow-up, clinical and ultrasound reassessment on Day 2. If the intra-uterine antero-posterior diameter on ultrasound examination was greater than 15 mm (or the gestational sac persisted), a second dose of misoprostol was administered or surgical evacuation was performed (failure of medical treatment). One hundred two patients were included, of whom 30 had an inevitable or threatened miscarriage and 72 had a missed abortion. The success rate defined by complete expulsion of the products of conception without resorting to surgical evacuation and without short-term complications, was 78.4% (80 patients). Two patients were lost to follow-up at 48 hours. Complete expulsion occurred within 2 days in 94% of cases. There were 13 emergency consultations, including 8 for expulsion pain and five surgical evacuations (3 for hemorrhagic expulsion, 2 for hemorrhagic retention). All together, there were 15 surgical evacuations for retention of the products of conception after 1 or 2 doses of misoprostol. There was one case of endometritis (1%). Thirty-four patients were hospitalized, 22 for surgical evacuation and 12 for expulsion pain. It is possible to use misoprostol as a single vaginal dose (800 microg) as out-patient treatment, since it gives satisfactory efficacy (80%) and is sufficiently safe (5% needing emergency surgery). However, out-patient management should only be performed after explaining the treatment and its risks clearly to the patient.

Mifepristone and vaginal misoprostol on the same day for abortion from 50 to 63 days’ gestation

In a previous study of 40 women up to 49 days’ gestation, our research center demonstrated that mifepristone 200 mg followed on the same day by misoprostol 800 μg vaginally produced abortion at rates similar to standard regimens which administer the two drugs 24 or 48 h apart. We performed this study to evaluate the same regimen in women with pregnancies at 50 to 63 days’ gestation. Forty women from 50 to 56 days’ gestation (Group 1) and 40 women from 57 to 63 days’ gestation (Group 2) inserted misoprostol vaginally 6 to 8 h after taking mifepristone. Participants were instructed to return 24 ± 1 h after using misoprostol for an evaluation that included transvaginal ultrasonography. Subjects who had not aborted received a second dose of misoprostol to administer 48 h after the mifepristone. All participants were to return 2 weeks later. Ultrasound examinations were performed in those who required a second dose of misoprostol to confirm the abortion was successful. At 24 h after receiving misoprostol, 37/40 (93%, 95% CI 80, 98%) and 36/40 (90%, 95% CI 76, 97%) women from Groups 1 and 2, respectively, had expelled the pregnancy. By follow-up 2 weeks after taking mifepristone, all 40 women in Group 1 (100%, 95% CI 91,100%) and 39/40 women in Group 2 (98%, 95% CI 87,100%) had complete abortions. One woman in the latter group who aborted within the first 24 h had an incomplete abortion treated by suction curettage. This pilot study suggests that mifepristone 200 mg, followed on the same day by misoprostol 800 μg vaginally, effects abortion in women 50 to 63 days’ gestation at rates comparable to regimens using longer dosing intervals between medications. Though this regimen is promising, larger randomized trials comparing it to standard regimens are needed before widespread use.

Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with decompensated cirrhosis: results of a double-blind placebo-controlled parallel group study

OBJECTIVES: Patients with cirrhosis are prone to develop renal failure upon administration of nonsteroidal anti-inflammatory drugs. The aim of the present study was to determine the safety and efficacy of misoprostol (400 μg) in two repeated doses for the prevention of ibuprofen-induced decrements in renal function in decompensated cirrhotics. METHODS: Patients were given ibuprofen (800 mg) with either misoprostol (n = 9) or a placebo (n = 10). Sixty minutes later another dose of misoprostol or the placebo was administered. Renal function tests were assessed by clearance techniques. RESULTS: Administration of ibuprofen with a placebo caused significant decreases in urinary output, inulin clearance, sodium excretion, osmolar clearance, free water clearance, and urinary prostaglandin E 2 excretion. Coadministration of ibuprofen and the first misoprostol dose maintained urinary output and sodium excretion, and caused an increase in free water clearance. These changes were maintained only for 1 h. Administration of the second dose of misoprostol temporarily improved inulin and creatinine clearances. Half the patients who received misoprostol suffered from episodes of chills, fever, and diarrhea. CONCLUSION: Ibuprofen causes renal dysfunction in decompensated cirrhotics, whereas misoprostol may have some protective renal effects, which are, however, short lived and clinically insignificant. Because of side effects, misoprostol should be used with caution in these patients.

Mifepristone followed on the same day by vaginal misoprostol for early abortion

We performed a pilot study to examine the clinical efficacy of mifepristone 200 mg followed on the same day by misoprostol 800 μg vaginally in women with pregnancies up to 49 days gestation. Forty women received mifepristone 200 mg after which they self-inserted misoprostol intravaginally 6 to 8 h later at home. Participants returned for an evaluation, including transvaginal ultrasonography, 24 ± 1 h after using the misoprostol. Participants who had not aborted received a second dose of misoprostol to administer 48 h after the mifepristone. All participants returned approximately 2 weeks after receiving mifepristone. At 24 h after receiving misoprostol, 37/40 (92%, 95% CI 81–98%) had ultrasonographic evidence of complete abortion. By follow-up 2 weeks after the mifepristone, 40/40 (100%, 95% CI 92–100%) women were felt to have complete abortions. One subject subsequently had a suction aspiration for an incomplete abortion on study Day 44. Nausea, vomiting, diarrhea, and warmth/chills occurred in 38%, 13%, 13%, and 60%, respectively. This pilot study suggests that mifepristone 200 mg, followed on the same day by misoprostol 800 μg vaginally, effects abortion at rates comparable to regimens using the standard time interval of 48 h between medications.

Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial

To examine the clinical efficacy of mifepristone 600 mg followed on the same day or two days later by misoprostol 400 microg orally in women undergoing medical termination of pregnancy whose pregnancies have a gestational age up to 49 days. Prospective, randomised trial. Clinical research office. Eighty-six women, requesting elective termination of a pregnancy which has a gestational age of < or = 49 days. After administration of mifepristone 600 mg, participants were randomised to take misoprostol six to eight hours later (Group 1) or 48 hours later (Group 2). Women returned for a follow up evaluation 24 +/- 1 hours after taking the misoprostol. Participants in Group 1 who had not aborted received a second dose of misoprostol to take 48 hours after the mifepristone. All women returned approximately two weeks after receiving mifepristone. If termination of pregnancy had still not occurred and the pregnancy was non-viable, the woman returned again in three weeks. Rate of complete abortion 24 hours after administration of misoprostol. At 24 hours after receiving misoprostol, 21/42 (50%, 95% CI 35%, 65%) women in Group I and 40/44 (91%, 95% CI 82%, 99%) women in Group 2 had complete abortions. By follow up two weeks later after the administration of mifepristone, 40/42 (95%, 95% CI 89%, 100%) women in Group 1 and 43/44 (98%, 95% CI 93%, 99%) women in Group 2 were known to have complete abortions. Nausea, vomiting or diarrhoea in women using the standard regimen (Group 2) occurred in 68%, 36%, and 20%, respectively. After treatment with mifepristone 600 mg, administration of misoprostol 400 microg orally on the same day is not as effective at causing abortion within the first 24 hours compared with the standard time interval of 48 hours between medications.

Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial

Objective To examine the clinical efficacy of mifepristone 600 mg followed on the same day or two days later by misoprostol 400μg orally in women undergoing medical termination of pregnancy whose pregnancies have a gestational age up to 49 days. Design Prospective, randomised trial. Setting Clinical research office. Participants Eighty-six women, requesting elective termination of a pregnancy which has a gestational age of ≤ 49 days. Methods After administration of mifepristone 600 mg, participants were randomised to take misoprostol six to eight hours later (Group 1) or 48 hours later (Group 2). Women returned for a follow up evaluation 24±1 hours after taking the misoprostol. Participants in Group 1 who had not aborted received a second dose of misoprostol to take 48 hours after the mifepristone. All women returned approximately two weeks after receiving mifepristone. If termination of pregnancy had still not occurred and the pregnancy was non-viable, the woman returned again in three weeks. Main outcome measures Rate of complete abortion 24 hours after administration of misoprostol. Results At 24 hours after receiving misoprostol, 21/42 (50%, 95% CI 35%, 65%) women in Group 1 and 40/44 (91%, 95% CI 82%, 99%) women in Group 2 had complete abortions. By follow up two weeks later after the administration of mifepristone, 40/42 (95%, 95% CI 89%, 100%) women in Group 1 and 43/44 (98%, 95% CI 93%, 99%) women in Group 2 were known to have complete abortions. Nausea, vomiting or diarrhoea in women using the standard regimen (Group 2) occurred in 68%, 36%, and 20%, respectively. Conclusions After treatment with mifepristone 600 mg, administration of misoprostol 400 μg orally on the same day is not as effective at causing abortion within the first 24 hours compared with the standard time interval of 48 hours between medications.

The efficacy of a 600-microgram misoprostol regimen for the evacuation of missed abortions

Objective: To evaluate the efficacy of a 600-μg misoprostol regimen for the evacuation of first-trimester missed abortions. Materials and Methods: Stable patients with missed abortion diagnosed between 6 and 14 weeks of gestation were given three treatment options. Patients in Group I chose misoprostol, 600 μg, intravaginally; Group II chose surgical dilation and curettage (D&C), and group III choose spontaneous resolution. After the options were presented to them, patients selected a group. In Group I, large cotton swabs were used to remove blood and mucus from the vaginal vault and cervix. Tablets of misoprostol were placed in the posterior fornix under direct visualization and 2–5 cc of normal saline was used to dissolve the tablet. Patients were observed for 2 hours for untoward side effects and discharged to home with instructions to follow up after 48 hours. Explanation of drug side effects and precautions about bleeding and infection also were provided. Multiple gestation was the only exclusion criterion. Results: A total of 110 patients were recruited for the study. Fifty-four patients (49%) chose Group I treatment, 5 (5%) selected Group II, and 51 (46%) selected Group III. Of the patients in Group I (n = 54), 45 (83%) successfully evacuated, 3 (6%) failed to evacuate and received surgical D&C, 9 patients (17%) required a second dose of misoprostol, and 6 (11%) were lost to follow-up after drug placement. Correcting for noncompliance in Group I (n = 48), the success rate increased from 83% to 94% for successful evacuation of the uterus. In group III, 25 patients (49%) spontaneously aborted and 26 (51%) did not return for follow-up. There were no major complications observed in patients who returned for follow-up, regardless of group. Conclusion: A 600-μg dose of misoprostol dissolved intravaginally followed by a rescue dose, when necessary, is highly successful and well tolerated in stable patients desiring prompt uterine evacuation for first-trimester pregnancy loss.

Misoprostol in labor induction.

The efficacy of a new dosing regimen of misoprostol, a recently introduced labor-inducing agent, was studied. Fifty-eight patients received 50 microg of misoprostol intravaginally and the dose was repeated every 3 hours until uterine contractions begin. Those who had an adequate contraction pattern, defined as three contractions in 10 minutes, were not given the repeat dose. Oxytocin augmentation, but not further misoprostol doses, was used in patients with an inadequate contraction pattern. The maximum total daily dose was 200 microg. The patients had the mean age of 28.9 +/- 5.4, the mean gestational age of 211.8 +/- 46.6 days, the mean gravidity of 2.5 +/- 1.2, the mean parity of 0.9 +/- 0.9 and the mean initial Bishop score of 1.6 +/- 1.8. The mean required dose of misoprostol was 120.5 +/- 54.7 microg and 10 of 58 patients required oxytocin augmentation. The mean induction of labor to delivery time was 701.5 +/- 404.0 minutes. When 3 cases who gave birth with caesarean section were excluded, the interval was 708.4 +/- 407.2 minutes. The mean 5th minute Apgar score of the newborns was 8.2 +/- 2.5. Two patients developed tachysystole after the second dose of misoprostol and were managed with vaginal irrigation and O2 supplementation successfully. Slight nausea and vomiting in 2 patients were the other adverse reactions. Our findings revealed that, 50 microg intravaginal misoprostol, combined with oxytocin augmentation when necessary, appears to be an effective and safe method of labor induction.

Vaginal Misoprostol Administered 1, 2, or 3 Days After Mifepristone for Early Medical Abortion

The conventional timing of misoprostol administration after mifepristone for medical abortion is 2 days, but more flexible intervals, which may make the regimen more convenient, have not been studied. To determine whether vaginal misoprostol administered 1, 2, or 3 days after mifepristone influences safety or effectiveness for abortion at up to 56 days' gestation. Prospective, randomized, open-label trial conducted from March 1998 to June 1999. Sixteen US primary care and referral abortion facilities. A total of 2295 healthy patients aged 18 years or older who were 56 or fewer days pregnant. Forty (1.7%) were lost to follow-up. Patients received 200 mg of oral mifepristone and were randomly assigned to self-administer 800 microg of vaginal misoprostol at home 1 (n = 745), 2 (n = 778), or 3 (n = 772) days later. Women returned to the clinic up to 8 days after mifepristone for ultrasonographic evaluation. A second dose of misoprostol was administered if the abortion was not complete. Patients with continuing pregnancy, excessive bleeding, or retained pregnancy tissue 5 weeks later received an aspiration curettage. Effectiveness of the procedure (ie, a complete medical abortion without surgical intervention), adverse effects, acceptability of the procedure based on patient questionnaires, reasons for surgical intervention, and adverse outcomes, compared among the study groups. Of the 2255 women completing follow-up, complete medical abortion rates were 98% (95% confidence interval [CI], 97%-99%) among those using misoprostol after 1 day, 98% (95% CI, 97%-99%) for those using misoprostol after 2 days, and 96% (95% CI, 95%-97%) among those using misoprostol after 3 days. Fifty-five subjects aborted before taking misoprostol, 9 had early surgery, and 103 did not take misoprostol on their assigned day. No blood transfusions were required. Cramping and nausea were the most common adverse effects reported, with similar percentages of patients in all 3 groups reporting such effects. Thirteen unexpected or serious adverse events occurred: 6 in those using misoprostol after 1 day; 4 in those using it after 2 days; and 3 in those using it after 3 days. Nearly all women (>90%) found the procedure to be acceptable. Our results suggest that vaginal misoprostol, 800 microg, can be used from 1 to 3 days after mifepristone, 200 mg, for early medical abortion, and need not be administered strictly 48 hours after mifepristone. JAMA. 2000;284:1948-1953.

A randomized comparison of mifepristone and self-administered oral or vaginal misoprostol for early abortion

In France, mifepristone in association with orally administered misoprostol is widely used for the early termination of pregnancy (up to 49 days' gestation). In other centers, mifepristone in association with vaginally administered misoprostol has also been used. The aim of the present study was to compare the efficacy and tolerance of mifepristone in association with misoprostol administered orally or vaginally for the termination of pregnancy of up to 49 days' gestation.A total of 237 women were enrolled in the study. All women received 600 mg mifepristone administered orally and 400 μg misoprostol administered either orally (n = 119) or vaginally (n = 118). A second dose of 400 μg misoprostol was administered if women had not expelled the pregnancy within 3 h. Women were randomized into treatment groups according to the day of their admission.The overall success rate was 98.7% and there was no significant difference in efficacy between the two groups. There was one treatment failure in the group in which misoprostol was administered orally. Of those women who aborted within 3 h of administration of the first dose of misoprostol, the route of administration of misoprostol did not influence the time to abortion. Of the women who received a second dose of misoprostol, the time to abortion was shorter in those who received misoprostol orally (52 min versus 77 min).Tolerance was assessed by visual analog scales and was similar for both groups. In both groups, women preferred the oral route of administration.

Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days

The aim of this study was to compare the effectiveness, side effects, and acceptability of one-third the standard dose of mifepristone, ie, 200 mg, and vaginal misoprostol 800 μg to induce abortion in subjects ≤56 days pregnant with subjects 57–63 days pregnant. A prospective multicenter trial enrolled healthy women ≥18 years, ≤63 days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 μg vaginally, and returned 1–4 days later for ultrasound evaluation. A second dose of misoprostol was administered, if necessary. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, or persistent products of conception 5 weeks later. Of 1137 subjects, 829 were in the ≤56 days pregnant group and 308 in the 57–63 days pregnant group. In all, 34 subjects had surgical intervention and 16 were lost to follow-up. Complete medical abortions occurred in 97% of subjects ≤56 days pregnant and 96% in the 57–63 days pregnant group. In all, 88% of subjects in the ≤56 days pregnant and 92% in the 57–63 days pregnant group bled within 4 h of using vaginal misoprostol. Comparing subjects ≤56 days pregnant with 57–63 days pregnant, there was less diarrhea (20% vs 29%, p = 0.002) and vomiting (33% vs 44%, p = 0.001), although side effects were acceptable to 82% of subjects in both groups. One subject in the ≤56 day group required a transfusion for delayed excessive bleeding. Although bleeding (p = 0.01) and pain (p = 0.02) were less acceptable in the 57–63 day group, 91% of subjects in both groups reported that the overall procedure was acceptable. In summary, low-dose mifepristone 200 mg and home administration of vaginal misoprostol 800 μg at 48 h were highly effective and acceptable to women ≤63 days pregnant, thereby expanding the number of women who can access a medical abortion.

A medical method of early pregnancy termination using tamoxifen and misoprostol

A study was undertaken to determine whether ingestion of the selective estrogen receptor modulator tamoxifen followed by vaginal administration of the prostaglandin misoprostol would be an effective medical method of elective termination of early pregnancy. A clinical trial was conducted with a study group of 100 healthy women with pregnancies of 56 days gestational age or less who desired elective pregnancy termination. Each subject ingested 20 mg of tamoxifen once daily for 4 days followed 4 days later by intravaginal placement of four 200 μg tablets of misoprostol. If abortion did not occur within the next 24 h a second dose of 800 μg of misoprostol was given. The main outcome measures were incidence of complete abortion, hemoglobin levels, duration of vaginal bleeding, and incidence of side effects. Complete abortion occurred in 92 (92%, 95% CI 86.7, 97.3%) of 100 subjects. Of these 92 women, four aborted after ingesting tamoxifen without use of misoprostol, 84 within 24 h after receiving a single dose of misoprostol, one 21 days following a single dose of misoprostol, and three after a second dose of misoprostol was administered. There were six (6.0%) complete treatment failures and two (2%) incomplete abortions that required a dilatation and curettage. The mean duration of uterine bleeding was 8.1 days (range 1–34 days) and there was a median decrease in hemoglobin level of 0.50 g/dL (+2.2 to −4.7 g/dL). Vomiting occurred in 28% of subjects and diarrhea in 8%. These initial data suggest that ingestion of tamoxifen followed by intravaginal misoprostol may be an effective, easily administered, and inexpensive method to electively induce complete abortion in pregnancies of 56 days gestational age or less. Additional studies are necessary to determine whether the addition of tamoxifen increases the success rate compared with that obtained with the use of vaginally administered misoprostol by itself.

Intravaginal misoprostol for medical evacuation of first trimester missed abortion

Objective: To evaluate the safety and efficacy of intravaginal misoprostol for medical evacuation of first trimester missed abortions. Methods: Seven women with a transvaginal ultrasound diagnosis of a first trimester missed abortion were treated with 800 μg of misoprostol. Four 200 μg misoprostol tablets were placed intravaginally, and a repeat dose of 800 μg was repeated if products of conception were not expelled in 12 hours. Results: Five of seven of the medical evacuations were successful. The average gestational age for the patients was 9 weeks with a range of 8 3/7 to 9 3/7 weeks. The average time from insertion to complete passage of products of conception was 18 hours with a range from 5 hours 10 minutes to 50 hours. Only one patient in the successful group required the second dose of misoprostol. One patient completely passed products of conception 2 weeks after the 2 doses of misoprostol and was considered a treatment failure. Another patient passed products of conception within 12 hours following insertion of the misoprostol but required a dilatation and curettage 3 days later and was also considered a treatment failure. Side effects included cramping in all patients, which was noted to be moderate in six and mild in one. One patient also had mild nausea, mild headache, and one episode of diarrhea. The average blood loss was estimated at 434 mL with a range from 171 to 871 mL. Conclusion: Intravaginal misoprostol for medical evacuation of first trimester missed abortions appears to be safe and effective and may be an alternative to dilatation and curettage.

Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a regimen for early abortion

Nonsteroidal anti-inflammatory drugs are frequently avoided by some investigators in protocols for medical abortion because of a concern over potential inhibition of prostaglandin action on uterine contractions. To evaluate the effects of nonsteroidal anti-inflammatory drugs on uterine cramping and resultant pregnancy expulsion, analgesic use by 449 participants with gestational age of ≤56 days in three previously reported medical abortion trials involving methotrexate and misoprostol was reviewed. Subjects from each of the three trials were included in this analysis only if they received 50 mg/m 2 methotrexate intramuscularly followed 3 or 7 days later by 800 μg misoprostol vaginally. Misoprostol administration was repeated if the abortion did not occur after the first misoprostol dose. A total of 416 subjects met the study criteria. For the women who took a nonsteroidal anti-inflammatory drug after the first dose of misoprostol, 132 246 (53.7%) aborted within 24 h. For those that did not take a nonsteroidal anti-inflammatory drug, 83 170 (48.8%, p = 0.38) aborted within 24 h. Similarly, 27 56 (48.2%) of the women who took a nonsteroidal anti-inflammatory drug aborted within 24 h of the second dose of misoprostol. However, only 32 145 (22.1%, p = 0.002) of the women who did not take a nonsteroidal anti-inflammatory drug aborted. Use of a nonsteroidal anti-inflammatory drug does not interfere with the action of misoprostol to induce uterine contractions and pregnancy expulsion in women receiving methotrexate and misoprostol for early abortion.

Abortion induced with methotrexate and misoprostol: A comparison of various protocols

Seven hundred fifty-six women had abortions induced with methotrexate and misoprostol. Various protocols were compared. In Group 1, phase 1, after receiving 50 mg/m 2 methotrexate IM, 289 women were randomized to receive either 750 or 500 μg of vaginal misoprostol. In Group 1, phase 2, 84 women who had failed to abort after one dose of misoprostol were randomized to receive either vaginal or oral routes for the second dose of misoprostol given on Day 8. In Group 2, a cohort of 226 women who received 60 mg/m 2 methotrexate were compared to the 289 women who received 50 mg/m 2 in Group 1. There were no differences in rates of effectiveness in the various trial groups. Side effects were greater with 60 mg/m 2 of methotrexate. In Group 3, a cohort of 241 women received the misoprostol in three vaginal doses 8 hr apart starting on Day 5, and were compared to the 289 women in Group 1 receiving one vaginal dose. In women whose medical abortion failed, fetuses were found to have limb abnormalities. In the total group of 756 women, 88.8% aborted successfully without surgical aspiration, with only minor side effects, and the acceptance rate was high. This study indicates that medical abortions induced with methotrexate and misoprostol are safe and effective, but more research is needed to find a more effective protocol.

A randomized trial comparing misoprostol three and seven days after methotrexate for early abortion

OBJECTIVE: Our purpose was to determine whether vaginal misoprostol 7 days rather than 3 days after methotrexate injection increases the percent of successful abortions on the day of misoprostol administration. STUDY DESIGN: A randomized controlled trial was performed in women requesting an abortion at ≤56 days' gestation. Eighty-six women were treated with methotrexate 50 mg/m 2 intramuscularly followed 3 days (group 1) or 7 days (group 2) later by misoprostol 800 μg. The misoprostol dose was repeated if the abortion did not occur. RESULTS: Complete abortion occurred in 38 of 46 (83%) patients in group 1 and 39 of 40 (98%) in group 2 ( p = 0.033). Of the women with complete abortions, 30 of 46 (b5%) in group 1 and 27 of 40 (68%) in group 2 aborted the same day as the first or second dose of misoprostol ( p = 0.823). Vaginal bleeding lasted 14 ± 5 (mean ± SD) days in group 1 and 17 ± 9 days in group 2. The remaining women aborted after a delay of 24 ± 6 days in group 1 and 28 ± 13 days in group 2. For these women vaginal bleeding lasted 18 ± 17 and 14 ± 7 days, respectively, and the human chorionic gonadotropin-β level was ≤25 IU/L by 22 ± 7 days after the abortion in group 1 and 19 ± 9 days in group 2. Treatment failures in group 1 were four continuing pregnancies (9%), two incomplete abortions (4%), and two women who requested surgical termination after receiving both medications (4%). The treatment failure in group 2 was an incomplete abortion. Methotrexate and misoprostol side effects were infrequent. CONCLUSIONS: Methotrexate and vaginal misoprostol are more effective abortifacients when the misoprostol is given 7 days rather than 3 days after methotrexate. This treatment regimen may offer an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.

Non-surgical abortion: who's for methotrexate?

When offered a choice of abortion through surgery or treatment with RU486, 60-70% of women choose RU486. Use of RU486 is, however, limited by the cost of the drug and the conservative marketing policy of Roussel Uclaf, holders of the patent. Methotrexate is a drug registered in many countries for several indications, including cancer therapy and psoriasis. In 1993, Creinin and Darney described its use as an abortifacient. Methotrexate when combined with prostaglandins works almost as well as mifepristone (RU486). It is inexpensive, off patent, and readily available in many parts of the world. Moreover, the US Food and Drug Administration has no jurisdiction over the off-label use of methotrexate as an abortifacient and an investigational new drug application is not required. Early trials to determine dosage are now being followed by larger studies of efficacy and side-effects. All of the experimental protocols have used a similar dosage regimen of methotrexate (approximately 80 mg) given intramuscularly, followed by 800 mcg of misoprostol per vagina 5-7 days later. Used before 56-63 days after the last menstruation, the regimen is 88-97% effective, and before 42 days methotrexate may be effective without misoprostol. Uterine emptying can take as long as two weeks and the decidua must be shed spontaneously, as with a spontaneous abortion. Even so, 90% of study participants reported that they would choose the method again if needed. Some investigators use a second dose of misoprostol, while the one in twenty aspiration procedures which seem to be needed with methotrexate abortion could be carried out as for any other minor operation by a trained person. Methotrexate together with the misoprostol costs less than US$7.00, even in the US. The author notes that while methotrexate is teratogenic in animals, and use before conception has been associated with spina bifida, use after conception has not been shown to be harmful and there in reassuring evidence of no long-term adverse effects upon subsequent pregnancies.

Methotrexate and misoprostol to terminate early pregnancy.

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. 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. 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. The combination of methotrexate and misoprostol represents a safe and effective alternative to invasive methods for the termination of early pregnancy.

Early Termination of Pregnancy with Mifepristone (RU 486) and the Orally Active Prostaglandin Misoprostol

The combination of mifepristone (RU 486) and a prostaglandin analogue given either intramuscularly or intravaginally is effective in terminating early pregnancy, but the prostaglandin component of the regimen is cumbersome to administer and has side effects. We conducted two studies to determine the efficacy of 600 mg of mifepristone followed by a small dose of misoprostol, an orally active prostaglandin E1 analogue, for the same purpose. In the first study, 505 women who had had amenorrhea for less than 50 days received 400 micrograms of misoprostol 48 hours after receiving mifepristone, if the pregnancy was not terminated within that period. In the second study, 390 women initially received the same treatment, but if the pregnancy was not terminated within four hours after the administration of misoprostol, they were offered an additional 200-micrograms dose of misoprostol. In study 1, the rate of success (termination of pregnancy and complete expulsion of the conceptus) was 96.9 percent (95 percent confidence interval, 94.1 to 97.7 percent)--similar to the success rate of approximately 95 percent for mifepristone followed by the intramuscular or intravaginal administration of prostaglandin. Abortion occurred in 2.9 percent of the women within 48 hours after the administration of mifepristone, in 60.9 percent within 4 hours after the administration of misoprostol, and in 33.2 percent thereafter. The failures included ongoing pregnancies in four women (0.8 percent) and incomplete abortions in nine (1.8 percent); two other women (0.4 percent) required vacuum aspiration for prolonged uterine bleeding. In study 2, pregnancy was terminated in 5.5 percent of the women before the administration of misoprostol and within four hours after the first dose of misoprostol in 69.1 percent. Among the 71 women who received a second dose of misoprostol, 67 had complete abortions, 2 had partial retention of the conceptus, 1 had synechia with ongoing pregnancy, and 1 had an ectopic pregnancy. One ongoing pregnancy, which was terminated by vacuum aspiration, was recorded among the 27 women who declined to take the second dose of misoprostol. The overall rate of success of the regimen with the optional second dose of misoprostol was 98.7 percent (95 percent confidence interval, 96.8 to 99.5 percent). No woman had any serious adverse event. The combination of mifepristone and misoprostol is effective for the termination of early pregnancy in terms of success, tolerance, safety, and practicality.