Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial.

CONTEXT: 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. OBJECTIVE: 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. DESIGN: Prospective, randomized, open-label trial conducted from March 1998 to June 1999. SETTING: Sixteen US primary care and referral abortion facilities. PATIENTS: 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. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

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, i.e., 200 mg, and vaginal misoprostol 800 microg to induce abortion in subjects < or =56 days pregnant with subjects 57-63 days pregnant. A prospective multicenter trial enrolled healthy women > or =18 years, < or =63 days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 microg 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 < or =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 < or =56 days pregnant and 96% in the 57-63 days pregnant group. In all, 88% of subjects in the < or =56 days pregnant and 92% in the 57-63 days pregnant group bled within 4 h of using vaginal misoprostol. Comparing subjects < or =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 < or =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 microg at 48 h were highly effective and acceptable to women < or =63 days pregnant, thereby expanding the number of women who can access a medical abortion.

PIP: The aim of this study was to compare the effectiveness, side effects, and acceptability of one-third the standard dose of mifepristone, i.e. 200 mg, and vaginal misoprostol 800 mcg to induce abortion in subjects 56 or fewer days pregnant with subjects 57-63 days pregnant. A prospective multicenter trial enrolled healthy women aged 18 years or older, 63 or fewer days pregnant, and wanting an abortion. Women received mifepristone 200 mg orally, followed by misoprostol 800 mcg 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 or fewer 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 or fewer days pregnant and 96% in the 57-63 days pregnant group. In all, 88% of subjects in the 56 days or fewer pregnant and 92% in the 57-63 days pregnant group bled within 4 hours of using vaginal misoprostol. Comparing subjects 56 or fewer days pregnant with 57-63 days pregnant, there was less diarrhea (20% vs. 29%, p = 0.0002) and vomiting (33% vs. 44%, p = 0.001), although side effects were acceptable to 82% of subjects in both groups. 1 subject in the 56 or fewer days 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 days 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 mcg at 48 hours were highly effective and acceptable to women 63 or fewer days pregnant, thereby expanding the number of women who can access a medical abortion.

Low-dose mifepristone 200 mg and vaginal misoprostol for abortion.

The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women > or = 18 years, up to 8 weeks pregnant, and wanting an abortion. The women received 200 mg mifepristone orally, self-administered 800 micrograms misoprostol vaginally at home 48 h later, and returned 1-4 days later for ultrasound evaluation. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, persistent products of conception 5 weeks later, or other serious medical conditions. Of the 933 subjects, 906 (97%) had complete medical abortions, 22 had surgical intervention, two were protocol failures, and three were lost to follow up. Of the 746 subjects who had no or minimal bleeding before misoprostol, 80% bled within 4 h and 98% within 24 h of using misoprostol. By day 7, 95% of women had a complete abortion. Side effects were aceptable in 85% of subjects, and 94% found the procedure acceptable. Low-dose mifepristone followed by vaginal misoprostol was highly effective as an abortifacient.

PIP: The effectiveness, side effects, and acceptability of 200 mg of mifepristone (one-third the standard dose) to induce medical abortion were investigated in a trial conducted at 7 centers in the US. 933 women with pregnancies up to 8 weeks' gestation were enrolled. They were given a 200-mg oral dose of mifepristone to be followed 48 hours later by home administration of 800 mcg of vaginal misoprostol and instructed to return 1-4 days later for ultrasound evaluation. 906 women (97%) experienced complete medical abortion, 22 required surgical abortion, 2 were protocol failures, and 3 were lost to follow-up. The most common indication for surgery was persistent or severe bleeding. Of the 746 women who had little or no bleeding before misoprostol administration, 593 (80%) bled within 4 hours and 731 (98%) within 24 hours of misoprostol. By day 7, 95% of women had experienced a complete abortion. The mean duration of bleeding was 17.4 days. 73% of subjects used an oral narcotic for pain. The most common mifepristone-related side effects were nausea and cramping; misoprostol-related side effects included cramping, fever, and chills. 74% found the pain related to the procedure acceptable and 85% rated its side effects as tolerable. Overall, 94% of subjects rated the medical abortion regimen as acceptable. These findings indicate that low-dose mifepristone is highly effective and acceptable as a self-administered abortifacient. The advantages of a lower dose of mifepristone include reduced manufacturing costs and less exposure to potential side effects.

Vaginal misoprostol administered at home after mifepristone (RU486) for abortion.

BACKGROUND: There have been no US studies published on the effectiveness, safety, time to bleeding, and acceptability of misoprostol administered by vagina at home and repeated, if needed, after mifepristone was administered for abortion in women up to 8 weeks pregnant. METHODS: A prospective trial was conducted with women up to 8 weeks pregnant wanting an abortion. After receiving mifepristone 600 mg orally, subjects self-administered vaginal misoprostol 800 micrograms at home 2 days later. Subjects returned within 7 days, and if the gestational sac was still present on ultrasound, a repeat dose of misoprostol was administered in the office. Subjects completed a daily symptom log and a questionnaire on the acceptability of the procedures. RESULTS: Of the 166 subjects, 163 (98%) had a complete medical abortion. Three subjects presented with persistent bleeding and an incomplete abortion from 27 to 35 days after taking mifepristone and required surgical intervention. Vaginal spotting or bleeding occurred in 104 (62%) subjects before taking misoprostol, and 18 (11%) did not use misoprostol. Bleeding occurred on average 3.5 hours (SD, 3.2) after taking misoprostol. Six (4%) subjects required a second dose of misoprostol. Gastrointestinal side effects were common, mild, and brief. One hundred fifty-nine (96%) subjects agreed that the procedure went well, and 146 (90%) agreed that home administration of misoprostol was acceptable. CONCLUSIONS: Two days after taking mifepristone, misoprostol administered by vagina was found to be safe, highly effective, and acceptable to women. Since only 6 subjects needed a second dose of misoprostol, conclusions about repeat doses are not possible. This procedure is a promising alternative to surgical abortion.

Methotrexate. A single agent for early abortion.

OBJECTIVE: To determine whether methotrexate as a single agent for induced abortion in pregnancies up to 5 weeks is as effective, has fewer side effects and is as acceptable to subjects as the combination of methotrexate and misoprostol. STUDY DESIGN: Women with no greater than a 5-week gestation were compared with a historical control group of consecutive women presenting for a medical abortion matched for gestational age. Subjects received intramuscular methotrexate on day 1. The study group received no misoprostol until day 21, when it was offered if the abortion had not yet occurred. The control group self-administered one or more doses of misoprostol within the first week after methotrexate. A complete abortion was defined by either negative transvaginal ultrasound or negative urine pregnancy test. All subjects completed a daily symptom log and satisfaction questionnaire. The analysis consisted of a comparison of the study group and control group for completion and timing of the abortion, symptoms and subject satisfaction. RESULTS: There were 40 study subjects and 53 controls. All subjects had a medical abortion without surgery. Ten (25%) of the 40 study subjects reached study day 21 without bleeding: 4 used misoprostol and 6 chose to wait for the abortion to occur spontaneously. One of the 10 subjects had persistent embryonic cardiac activity at 21 days and aborted after misoprostol. The mean number of days to bleeding was 15.5 days (SD 7.8 days) for the study group as compared with 8.1 days (SD 11.3) (P = .0003) for the control group. There was no significant difference in the number of days of bleeding, gastrointestinal side effects or reported subject satisfaction. CONCLUSION: While methotrexate as a single agent was effective in inducing abortion in early pregnancy, 15% of the study subjects finally used misoprostol, the abortion took significantly longer, and side effects were not less common as compared with those in subjects who received the combination of methotrexate and misoprostol.

Methotrexate and misoprostol for early abortion.

OBJECTIVES: This study examined the effectiveness of an abortion by methotrexate and misoprostol, including side effects, subjects' satisfaction, and optimal treatment strategies. METHODS: The study evaluated a prospective ongoing trial of women with an 8-week gestation or less wanting an abortion. Subjects received intramuscular methotrexate (50 mg per m2 of body surface area) on day 1. Subjects self-administered misoprostol 800 micrograms orally or as a vaginal suppository or vaginal tablets either on day 3 to 4 or day 5 to 7. Repeat misoprostol 800 micrograms doses were used vaginally if there was no significant bleeding and the gestation was less than 12 weeks. Subjects with continuing pregnancies had a surgical abortion. Subjects completed a daily symptom log and a satisfaction questionnaire. A successful medical abortion was defined by vaginal bleeding without surgical intervention and either a negative urine pregnancy test or a negative transvaginal ultrasound. RESULTS: Of the 282 subjects, 274 (97%) had a medical abortion. Eight (3%) subjects required surgical intervention--four for continued pregnancies and four for excessive bleeding. One hundred and sixty-two (57%) subjects required only one dose of misoprostol and started bleeding, on average, 6.2 hours later. One hundred and twelve subjects (40%) required an average of 2.5 misoprostol doses and started bleeding, on average, 12.4 days after initial methotrexate injection. Misoprostol was more effective vaginally than orally. Gastrointestinal side effects were common, mild, and brief. Eighty-eight percent of the subjects agreed that the procedure went well. Subjects monitored with ultrasound completed the study sooner than those followed by beta-hCG levels. CONCLUSION: Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks' gestation. The procedure is a promising alternative to surgical abortion.

Methotrexate and misoprostol when surgical abortion fails.

OBJECTIVE: To describe the use of methotrexate and misoprostol to induce abortion in pregnancies up to 8 weeks when uterine or cervical anomalies make suction curettage difficult or impossible. METHODS: Four consecutive women, 8 weeks pregnant or less and with failed suction curettage, were given methotrexate 50 mg per square meter intramuscularly followed by a misoprostol 800-microgram suppository 72 hours later. A repeat dose of a misoprostol 800-microgram vaginal suppository was administered on day 4 if there was no bleeding, and an additional dose was given if the repeat beta-hCG titer had not decreased by at least 50%. Subjects were followed-up with serum or urine hCG assays. Complete abortion was defined by vaginal bleeding and a negative urine pregnancy test. Subjects completed a daily symptom log and a satisfaction questionnaire when the abortion was complete. RESULTS: The four women referred after failed suction curettage had the following anatomic problems: a uterus bicornis bicollis, a bicornuate uterus, uterine leiomyomas, and cervical stenosis resulting from previous laser surgery. All subjects had a complete abortion from methotrexate and misoprostol. Mild gastrointestinal side effects were reported by all four subjects: nausea (two subjects), vomiting (two), and diarrhea (two). The satisfaction questionnaire revealed that all subjects agreed with the statements that "Overall, the procedure went well" and "I would recommend this procedure over a surgical abortion." CONCLUSION: Methotrexate and misoprostol can induce an abortion when uterine or cervical anomalies make suction curettage difficult or impossible.

Combined methotrexate and misoprostol for early induced abortion.

OBJECTIVE: To determine the effectiveness and side effects of and subject satisfaction with an induced abortion by administration of methotrexate and intravaginal misoprostol. SUBJECTS AND DESIGN: Prospective trial of 100 consecutive pregnant women aged 18 years or older at 8 weeks' gestation or less and wanting an abortion. INTERVENTIONS: Intramuscular administration of 50 mg of methotrexate per square meter of body surface area on day 1 and a misoprostol 800-micrograms vaginal suppository on day 3. Administration of misoprostol was repeated the following day if no bleeding occurred after the first dose. PROTOCOL: After pregnancy dating by clinical criteria, subjects were followed up with serum beta-human chorionic gonadotropin (beta-hCG) determinations on days 1, 7, and 14 and a high-sensitivity urine hCG test every 2 weeks until the value was less than 10 IU/L. Subjects completed a daily symptom log and satisfaction questionnaire on day 14. MAIN OUTCOME MEASURES: Complete abortion as defined by vaginal bleeding and a beta-hCG value of less than 10 IU/L without surgical intervention, complications and side effects, and patient satisfaction. RESULTS: Ninety-seven subjects had a complete abortion and one subject had vaginal bleeding and a 94% decrease of her beta-hCG value on day 7 but was subsequently unavailable for follow-up. Two subjects required surgical procedures: one with a continued pregnancy and one for excessive bleeding. No failures or complications occurred in early gestations prior to 45 days from the last menstrual period. Seventy-three percent responded to misoprostol treatment with bleeding within 12 hours and had a mean decrease of 90% in their beta-hCG value on day 7. Twenty-seven percent had no immediate bleeding response to misoprostol administration, began bleeding on day 10 (SD, 8 days), and had a mean decrease of 10% in their beta-hCG value on day 7. Seventy percent reported nausea; 46%, diarrhea; and 23%, vomiting. Ninety-three percent agreed that the procedure was acceptable and 95% would recommend the procedure. CONCLUSIONS: Methotrexate and misoprostol were effective in inducing an abortion up to 8 weeks. Home administration of a compounded misoprostol vaginal suppository was successful. Although gastrointestinal tract side effects were common, women found the procedure and its side effects acceptable.

Culdocentesis.

Culdocentesis is a procedure to obtain free fluid from the cul de sac of women. Physicians who provide comprehensive or gynecologic care to women should be capable of this procedure. The main indications are suspected ectopic pregnancy and suspected acute salpingitis or pelvic inflammatory disease. Although the procedure is not difficult or dangerous, many fine points of technique improve the outcome. Results are usually clear-cut and provide immediate and critical information for the management of the patient.

Second-trimester spontaneous abortion, the IUD, and infection.

Nineteen cases of spontaneous second-trimester abortion associated with the intrauterine device (IUD) are reviewed and compared to 30 cases of spontaneous second-trimester abortion not associated with the IUD. Fifteen of the IUD's were Dalkon shields and four were Lippes loops. 16 of the 19 IUD-associated abortions began either with prolonged rupture of membranes or signs and symptoms of infection. Infection occurred in 18 or 19 of the cases (95%) but only 30% of the comparison group. Eleven major complications occurred in eight patients in the IUD group but only 8 complications occurred among 7 patients in the comparison group. It is suggested that when the IUD remains in utero during pregnancy, it may be a causal factor in second-trimester spontaneous abortion, and that intrauterine infection is the distinguishing characteristic of such cases. Mechanisms are suggested by which the IUD might cause infected abortion.