Steven H. Eisinger

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.

Low-dose mifepristone for uterine leiomyomata.

OBJECTIVE To compare the effect of 5 and 10 mg of mifepristone on uterine leiomyoma size and symptoms, and to measure side effects. METHODS Forty premenopausal women with large, symptomatic leiomyomata were randomized to receive either 5 or 10 mg of mifepristone daily for 6 months in an open-label study. Uterine volume was measured at bimonthly intervals by sonography. Serum concentrations of hemoglobin levels, follicle-stimulating hormone, and liver enzymes were obtained, and endometrial samples, symptoms, and menstrual bleeding were also assessed. RESULTS Nineteen of 20 subjects taking 5 mg and all 20 subjects taking 10 mg completed all 6 months of the study. Mean uterine volume shrank by 48% (P < .001) in the 5-mg group and 49% (P < .001) in the 10-mg group, a nonsignificant difference. Leiomyoma-related symptoms were comparably reduced in both groups. Amenorrhea occurred in 60–65% of both groups. Hemoglobin levels increased by 2.5 g/dL in anemic subjects. The incidence of hot flashes increased significantly over baseline in the 10-mg group but not in the 5-mg group. Simple endometrial hyperplasia occurred in 28% of all subjects, with no difference between groups. No atypical hyperplasia was noted. CONCLUSION Mifepristone in doses of 5 mg or 10 mg results in comparable leiomyoma regression, improvement in symptoms, and few side effects. Further study is needed to assess the long-term safety and efficacy of low-dose mifepristone.

Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial.

OBJECTIVE: To assess the effect of low-dose mifepristone on quality of life, pain, bleeding, and uterine size among women with symptomatic leiomyomata. METHODS: Forty-two women with symptomatic uterine leiomyomata and uterine volume of 160 mL or more were randomized to mifepristone, 5 mg daily, or placebo for 26 weeks. Quality of life (Uterine Fibroid Symptoms Quality of Life Questionnaire and Medical Outcomes Study 36-Item Short Form survey) and uterine and leiomyoma size (ultrasonography) were assessed at baseline, and at 1 month, 3 months, and 6 months of treatment. Bleeding (daily logs and pictorial charts) and pain (McGill Pain Questionnaire) were assessed monthly. Endometrial pathology was assessed at baseline and 6 months. RESULTS: Forty-two women were randomized; 37 women completed all 6 months. Women randomized to mifepristone showed an improvement in leiomyoma-specific quality of life. Forty-one percent became amenorrheic, rates of anemia improved, and adjusted uterine size was reduced by 47%. Compared with the placebo group, improvements in these outcomes in the treatment group were significantly greater (P<.05 to .001). There were no significant differences in adverse effects between the groups. No endometrial hyperplasia was noted in any participant. CONCLUSION: Low-dose mifepristone improves leiomyoma-specific quality of life and reduces leiomyoma size among women with symptomatic leio-myomata. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov www.clinicaltrials.gov NCT00133705 LEVEL OF EVIDENCE: I

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.

Distinguishing features of endometrial pathology after exposure to the progesterone receptor modulator mifepristone

There is growing interest in the use of progesterone receptor modulators such as mifepristone for treatment of gynecologic and other conditions, but interest in progesterone receptor modulators is dampened by the effects of the agents on the endometrium. In this study, we examined the endometria of women exposed to mifepristone for treatment of leiomyomas in doses of 2.5 and 5 mg and compared them to unexposed endometria. We assessed the reliability of these features by comparing agreement in ratings between pathologists who were blinded to each others readings. We assessed distinguishing features between exposed and unexposed groups by comparing frequency of features between groups. We found that key features could be reliably assessed by pathologists experienced in endometrial pathology. We observed several features (nonsynchronous endometrium, large fluid filled glands, and abnormal blood vessels) that distinguished endometrial samples that were and were not exposed to the drug. These findings suggest several features that can be tracked during studies involving mifepristone and, potentially, other progesterone receptor modulators.

Mifepristone and misoprostol for early abortion when no gestational sac is present

The study was conducted to determine whether the administration of mifepristone followed by vaginal misoprostol can induce an abortion in early pregnancy when no gestational sac is present on sonogram. This report presents a prospective, pilot study of 30 healthy adult women, pregnant and seeking an abortion, and with no gestational sac on sonogram. All women had a baseline serum chorionic gonadotropin (hCG) level measured prior to using mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 48 h later, and then returned up to 4 days later for a repeat sonogram and serum hCG level. Women with initial hCG levels > 2000 IU/L were evaluated for ectopic pregnancy. At the first follow-up visit, if the hCG decreased by >50%, the women were followed with home pregnancy (25 IU/L) tests weekly until negative. If the levels did not decrease by 50%, a second dose of misoprostol was given. Surgical intervention was indicated for persistent hCG levels or excessive bleeding. Of the 30 women enrolled, the mean number of days of amenorrhea was 40 (SD 9) days. Two women had surgical intervention for continuing pregnancy, 2 had ectopic pregnancies, and 1 was lost to follow-up. Complete medical abortions occurred in 25/30 (88%) women, but when recalculated, in 25/27 (93%) women who completed the protocol and who did not have an ectopic pregnancy. There was 1 adverse event in a woman with an ongoing pregnancy who then received methotrexate. She was hospitalized a day later with a complicated pelvic infection and likely methotrexate-induced pneumonitis. Twenty-three women had a decrease in hCG at first follow-up visit of >50%. All 27 women who completed the protocol found the overall regimen acceptable. Mifepristone followed at 48 h by vaginal misoprostol were effective and acceptable in inducing an abortion in very early pregnancy. There may be a higher incidence of failure in very early pregnancies. Documentation of a complete abortion by hCG level is necessary to ensure the pregnancy is neither ongoing nor ectopic.

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-μg vaginal suppository 72 hours later. A repeat dose of a misoprostol 800-μg suppository was administered on day 4 if there was no bleeding, and an additional dose was given if the repeat β-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.

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 IUDs 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.