Ability of the clinician and patient to predict the outcome of mifepristone and misoprostol medical abortion

We performed this analysis to evaluate the ability of both women and their clinicians to predict pregnancy expulsion after using mifepristone and misoprostol for medical abortion up to 63 days gestation. Women who participated in a multicenter, randomized trial comparing misoprostol 6-8 h vs. 23-25 h after mifepristone attended a follow-up visit approximately 7 days after mifepristone treatment. Each subject was asked if she felt she had expelled the gestational sac. Clinicians also assessed if the sac had been expelled based on the woman's history. Vaginal ultrasonography was then performed to assess the uterine cavity. Of the 1080 women enrolled in the multicenter study, 931 (86.2%) who attended the first follow-up visit by study day 12 and did not have a uterine suction aspiration prior to this visit were included in this analysis. Vaginal ultrasonography at the first follow-up visit demonstrated expulsion in 915 [98.3%, 95% confidence interval (CI): 97.2-99.0] women. Overall, sensitivity, specificity, and positive and negative predictive values for subjects were 96.5%, 31.3%, 98.8% and 13.5%, respectively. When both the clinician and patient felt that the gestational sac had passed (n = 880 [94.5%, 95% CI: 92.9-95.9]), expulsion was confirmed by sonography in 99.1% (95% CI: 98.2-99.6) of cases. Women and clinicians are very accurate at determining expulsion of gestational sac during medical abortion with mifepristone and misoprostol without ultrasonography or a physical examination.     

Oral mifepristone and buccal misoprostol administered simultaneously for abortion: a pilot study

BACKGROUND: Simultaneous oral mifepristone and vaginal misoprostol has a 24-h expulsion rate of approximately 90% when used for abortion through 63 days' gestation. This pilot study sought to determine if a simultaneous regimen using buccal misoprostol would be similarly effective and merit further investigation. STUDY DESIGN: One hundred twenty women were enrolled into three equal groups by gestational age: < or =49 days (Group 1), 50-56 days (Group 2) and 57-63 days (Group 3). After swallowing 200 mg of mifepristone, subjects received 800 mcg buccal misoprostol. Participants returned in 24+/-1 h for evaluation of expulsion by ultrasonography. Women with a persistent gestational sac received 800 mcg vaginal misoprostol. Further follow-up occurred at 1, 2 and 5 weeks by telephone or in person, as appropriate. Sample sizes for each group were estimated with the aim of establishing a 24-h expulsion rate of 90% (95% CI=76-95). RESULTS: The 24-h expulsion rates for Groups 1, 2 and 3 were 73% (95% CI=56-85), 69% (95% CI=52-83) and 73% (95% CI=56-85), respectively. Common side effects were nausea (62%), vomiting (33%) and diarrhea (48%), which did not differ by gestational age. Forty-three percent of subjects found the taste of buccal misoprostol objectionable; 30% found buccal retention uncomfortable or inconvenient, and 10% reported oral irritation, sensitivity, numbness or oral ulcers. CONCLUSIONS: Simultaneous oral mifepristone and buccal misoprostol had a lower-than-hypothesized expulsion rate at 24 h. Although overall success rates at 7 or 15 days could have been higher than those observed at 24 h, we believe that this regimen does not warrant further study.     

Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion.

Mifepristone was recently approved in the United States. Regimens with shorter intervals may be more acceptable. The objective of this study was to determine whether the oral route of misoprostol was as effective as the vaginal route of misoprostol 1 day after mifepristone. A prospective, open-labeled, randomized trial of healthy adult women up to 63 days pregnant and wanting a medical abortion were randomized to use either two doses of oral misoprostol 400 microg taken 2 h apart or misoprostol 800 microg vaginally. Women self-administered misoprostol 1 day after taking one-third of the standard dose of mifepristone (200 mg) orally. Women then returned to the clinic up to 5 days later for a repeat sonogram evaluation. A dose of vaginal misoprostol was administered to women with a continuing pregnancy who then returned 1 day later to Day 15. The primary outcome measures were a complete medical abortion by the first or by the second follow-up visits. Surgical intervention was indicated for continuing pregnancy at the second follow-up visit, excessive bleeding, or persistent products of conception 5 weeks later. One thousand one hundred sixty-eight women were enrolled. Of the 1144 (98%) women who complied with their random assignment, two oral doses of misoprostol (800 microg total) were 90% effective at inducing an abortion by the first follow-up visit, compared with one dose of misoprostol by vagina of 97% (chi(2) = 23.95, p = 0.001). By the second follow-up visit, the complete abortion rate was 95% for oral misoprostol and 99% for vaginal misoprostol (chi(2) = 21.76, p = 0.001). There were minimal differences in side effects. Women preferred the oral route. The trial demonstrated that although two doses of oral misoprostol were effective, the vaginal misoprostol was more effective at inducing an early medical abortion at 1 day after low-dose mifepristone, and the regimen could be extended to 63 days gestation.     

Medical abortion outcomes after a second dose of misoprostol for persistent gestational sac

BACKGROUND: We sought to examine outcomes after a second dose of misoprostol was given at a 1-week follow-up visit after medical abortion for the presence of a persistent gestational sac (GS) on ultrasound examination. STUDY DESIGN: We examined outcomes in women who were enrolled in two randomized trials of medical abortion regimens. Pregnant women up to 63 days' gestation received mifepristone followed by misoprostol 800 mcg vaginally either 24 h later, 6-8 h later or within 15 min. Participants in both studies returned for an evaluation, including transvaginal ultrasonography, approximately 7 days after initiating treatment. We included women with a GS present at the follow-up visit. Subjects who had not expelled the GS received a second dose of misoprostol 800 mcg vaginally. Participants returned approximately 1 week later and were contacted by telephone 5 weeks after treatment. RESULTS: Of 1972 women who had a follow-up ultrasound examination within 11 days of treatment, a persistent GS was identified in 82 women (4.2%) of whom 68 opted to receive a second dose of misoprostol. All 68 women returned for follow-up evaluation and 42 (62%) expelled the GS. In the 26 women with an embryonic pole within the persistent sac, expulsion occurred in 5 (36%) of 14 with and 7 (54%) of 13 without gestational cardiac activity (GCA) (p = .45). Of the 14 pregnancies with GCA, only 5 (36%) had GCA at follow-up. CONCLUSIONS: More than half of women with a persistent GS after medical abortion will expel the pregnancy when treated with a second dose of misoprostol. One-third of women who have a GS with cardiac activity will expel the GS with a second dose of misoprostol, making a second dose a reasonable option.     

A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days

INTRODUCTION: In the interest of decreasing the amount of time it takes to achieve a medical abortion, we performed a pilot study to evaluate the simultaneous administration of mifepristone and vaginal misoprostol for women with gestation from 50 to 63 days. MATERIALS AND METHODS: Forty women were enrolled with undesired pregnancies from 50 to 56 days' gestation (group 1) and 40 from 57 to 63 days' gestation (group 2). All women used misoprostol 800 mug vaginally immediately after having swallowed the 200 mg mifepristone tablet. Follow-up evaluations with transvaginal ultrasonography occurred at 24 h and 2 weeks after treatment. RESULTS: The 24-h expulsion rates were 88% (95% CI, 77-98) and 83% (95% CI, 7-94) in groups 1 and 2, respectively. The complete abortion rates at 2 weeks were 93% (95% CI, 84-100) and 90% (95% CI, 81-99), respectively. DISCUSSION: Simultaneous administration of oral mifepristone and vaginal misoprostol provides 24-h expulsion rates in women with gestation from 50 to 63 days, comparable to those reported in the medical literature for standard treatment regimens. Further study of this regimen in a large randomized trial is warranted.     

Simultaneous very low dose mifepristone and vaginal misoprostol for medical abortion

OBJECTIVE: This pilot study was designed to evaluate the outcome of medical abortion following simultaneous mifepristone (100 mg) and misoprostol (800 microg). METHODS: Enrollees had gestational ages up to 56 days and desired a medical abortion. They received 100 mg of mifepristone orally and 800 microg of misoprostol vaginally. Follow-up examination occurred in 2-7 days. A phone call 3 weeks later assessed symptoms and acceptability. A 95% success rate, as seen in higher dose studies, gives a 95% confidence interval of 88-100% for 40 subjects. RESULTS: Forty women were enrolled; 39 women had follow-up visits. Completed medical abortion was confirmed for 35 (90%) of 39 women. Four women had uterine aspiration. Two patients required repeat misoprostol. Median time from medication to abortion was 7 h. Most women (92%) strongly preferred taking all medications in the clinic. CONCLUSIONS: The simultaneous administration of vaginal misoprostol with 100 mg of oral mifepristone had the outcome of completed abortion within the predicted confidence interval. In addition, simultaneous dosing was highly acceptable.     

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.     

Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy

This prospective, open-label, randomized trial of healthy adult women up to 9 weeks pregnant compared mifepristone 200 mg followed 2 days later with misoprostol 400 microg orally versus misoprostol 800 microg vaginally. The study was interrupted after the oral misoprostol group experienced a higher than expected failure rate. This treatment was discontinued and another substituted consisting of oral misoprostol 800 microg divided into two doses two hours apart. Women returned for a follow-up visit from Day 4 to 8. All women with a continuing pregnancy received a repeat dose of misoprostol vaginally and returned before Day 15. The primary outcome measure was a complete medical abortion without surgical intervention at the first visit. Of the 1045 women enrolled, 1011 had complete data: Group 1 (220) used oral misoprostol 400 microg, Group 2 (269) used oral misoprostol 800 microg, and Group 3 (522) used vaginal misoprostol 800 microg. At first follow-up visit, the primary outcome, that is, a complete abortion, was 84% for Group 1, 92% for Group 2, and 96% for Group 3, p < 0.001. After a second dose of vaginal misoprostol in women with on-going pregnancies at their first follow-up visit, the complete abortion rates were 91%, 95%, and 98%, respectively, p < 0.001. There were minimal differences in side effects, onset of bleeding and overall acceptability in the three groups. Mifepristone 200 mg followed by vaginal misoprostol 2 days later was more effective at inducing an abortion up to 9 weeks of pregnancy than the same dose of mifepristone followed by oral misoprostol.     

Clinicians' perception of sonogram indication for mifepristone abortion up to 63 days

One barrier in the US to wider acceptance of mifepristone for abortion is the additional cost of the routine use of two sonograms, that is, for pregnancy dating and confirmation of a complete abortion. The purpose of this study is to document how the accuracy of medical abortion clinicians experienced with pelvic exams and dating pregnancies in assessing gestational age at the first visit compared with sonograms, and to identify the factors influencing whether they perceive that sonograms are desired or indicated at the first and follow-up visits. This was a prospective study of 1016 women wanting to participate in a medical abortion trial. After informed consent, clinicians (1) dated the pregnancy before routine sonography and (2) determined whether a sonogram was indicated. Women with sonographic pregnancies of less than 63 days were eligible for mifepristone followed by misoprostol 48 h later. Women returned on Day 4 to Day 8, and clinicians performed a clinical assessment of whether the abortion was complete and determined whether a sonogram was indicated. Fifteen sites participated. Advanced-level providers performed 56% of the assessments. When clinicians assessed a pregnancy under 43 days gestation, they perceived that a sonogram was "not indicated" in 60% of these women. This percentage increased to 66% at 43-49 days gestation, and declined to 46% of women assessed at more than 49 days. Clinicians correctly assessed gestational age as no more than 63 days in 87% of women. In only 1% (14/1013) of their assessments did clinicians underestimate gestational age. In 7/24 (29%) women with a persistent gestational sac, clinicians did not indicate the need for sonography when it was likely indicated. We conclude that the clinicians in our study felt confident in not using sonography in most cases. If clinicians monitor hCG levels to identify any ectopic or continuing pregnancies, medical abortion can be safely performed without sonography.     

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 microg 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 microg vaginally, effects abortion at rates comparable to regimens using the standard time interval of 48 h between medications.     

A comparison of transabdominal and transvaginal ultrasonography for determination of gestational age and clinical outcomes in women undergoing early medical abortion

Background

We sought to establish the accuracy of abdominal ultrasonography in determining gestational age and identifying the presence of a gestational sac and embryonic pole before and after medical abortion.

Methods

We included all 120 women enrolled in a study of simultaneous oral mifepristone and buccal misoprostol for abortion through 63 days' gestation. Vaginal and abdominal ultrasound examinations were performed before and 24 h after medication administration. Visualization of a gestational sac and embryonic pole and presence or absence of cardiac activity were recorded. Sensitivity and specificity were calculated with the results from vaginal ultrasonography as the gold standard. The effect of body mass index (BMI) on ultrasound findings was also assessed.

Results

Before treatment, the sensitivities of abdominal ultrasonography were 100% (95% CI 97-100) and 68% (95% CI 58-77) for presence of a gestational sac and an embryonic pole, respectively. Overall, abdominal imaging underestimated mean gestational age by 1.6 days (95% CI 1.0-2.2). After treatment, abdominal ultrasonography missed three of 34 retained gestational sacs (sensitivity 91%, 95% CI 76-98%). Fourteen women had gestational cardiac activity by vaginal ultrasound at follow-up. Abdominal imaging identified the gestational sac in all cases, but cardiac motion was only visible in 10 (71%, 95% CI 42-92%). For every 10-point increase in BMI, the odds ratio for missing an embryonic pole at baseline was 2.8 (95% CI 1.5-5.0).

Conclusions

Abdominal ultrasonography is sensitive for diagnosing the presence or absence of a gestational sac, but less sensitive at detecting an embryonic pole. This may lead to a small underestimation of gestational age and missing a continuing pregnancy at follow-up when one exists.     

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 microg 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 microg 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.     

The efficacy of medical abortion: a meta-analysis

Multiple clinical studies demonstrate the efficacy of medical abortion with mifepristone or methotrexate followed by a prostaglandin analogue. However, assessing predictors of success, including regimen, is difficult because of regimen variability and a lack of direct comparisons. This meta-analysis estimates rates of primary clinical outcomes of medical abortion (successful abortion, incomplete abortion, and viable pregnancy) and compares them by regimen and gestational age. We identified 54 studies published from 1991 to 1998 using mifepristone with misoprostol (18), mifepristone with other prostaglandin analogues (23), and methotrexate with misoprostol (13). Data abstracted from studies included regimen details and clinical outcomes by gestational age. We found that efficacy decreases with increasing gestational age (p<0.001), and differences by regimen are not statistically significant except at gestational age > or =57 days. For gestations < or =49 days, mean rates of complete abortion were 94-96%, incomplete abortion 2-4%, and ongoing (viable) pregnancy 1-3%. For gestations of 50-56 days, the mean rate of complete abortion was 91% (same for all regimens), incomplete abortion 5-8%, and ongoing pregnancy 3-5%. For > or =57 days, success was lower for mifepristone/misoprostol (85%, 95% confidence interval 78-91%) than for mifepristone/other prostaglandin analogues 95% (CI 91-98%, p = 0.006). For mifepristone/misoprostol, using > or =2 prostaglandin analogue doses seems to be better than a single dose for certain outcomes and gestational ages. We conclude that both mifepristone and methotrexate, when administered with misoprostol, have high levels of success at < or =49 days gestation but may have lower efficacy at longer gestation.     

A pilot study on the use of letrozole with either misoprostol or mifepristone for termination of pregnancy up to 63 days

Background

Letrozole is a third-generation selective aromatase inhibitor. Animal data suggested that it might be useful in medical abortion. We performed two pilot studies to assess the feasibility of using letrozole in combination with either mifepristone or misoprostol for termination of pregnancy up to 63 days.

Study Design

We recruited 40 subjects who requested legal termination of pregnancies up to 63 days. Medical abortion was performed with letrozole 7.5 mg daily for 2 days followed by 800 mcg vaginal misoprostol in 20 subjects and letrozole 7.5 mg combined with 200 mg mifepristone in another 20 subjects.

Results

The mean induction-to-abortion interval of the regimen of letrozole and misoprostol was 9.1 h (median 7.9 h, range 2.7–23.6 h). The complete abortion rate was 80% (95% CI: 56.3–94.3%). For those with gestation of ≤49 days, the complete abortion rate was 87.5% (14/16; 95% CI: 61.7–98.5%). The mean induction-to-abortion interval of letrozole combined with mifepristone was 90.1 h (median 93.4 h, range 66.0–121.2 h). The complete abortion rate was 71.4% (95% CI: 47.8–88.7%).

Conclusion

These preliminary results suggest that a regimen of letrozole and misoprostol may be useful in medical abortion, but the combination with mifepristone is less effective and takes longer. Randomized studies comparing letrozole and misoprostol to misoprostol alone are warranted.     

舌下含服米索前列醇对药物流产结局影响的临床研究

目的:探讨舌下含服米索前列醇对药物流产结局的影响。方法:将208例妊娠天数<49天的早孕妇女随机分组,对照组常规口服米非司酮配伍米索前列醇,观察组口服米非司酮配伍舌下含服米索前列醇,药物剂量相同。结果:观察组和对照组完全流产率分别为96.0%和89.1%,不全流产率为3.0%和5.9%,流产失败率为1.0%和5.0%(P<0.05);两组阴道持续出血时间分别为12.8±4.4天和13.1±4.5天,两组出血量无显著性差异;观察组中出现寒颤的例数比对照组明显增加(P<0.001),其它副反应比较无显著性差异(P>0.05)。结论:应用米非司酮片配伍舌下含服米索前列醇可提高完全流产率,值得临床推广。     

药物终止16～24周妊娠的临床研究

目的;比较米非司酮合并米索前列醇与利凡诺羊膜腔内注射终止16～24周妊娠的临床效果及各自的优缺点。方法:将来自上海市13所医院的829例孕16～24周要求终止妊娠的妇女,随机分成2种不同的治疗组。组Ⅰ(双米组):415例,米非司酮 100mg/qd连服两天(总量 200mg),第 3天晨阴道内放置米索前列醇 0.4mg,每 12小时重复 一次,最多3次;组Ⅱ(利凡诺组):414例,羊膜腔内注射利凡诺100mg,不加任何辅助方法,胎儿胎盘娩出后常规清宫。结果:两组流产成功率分别为91.6％和92.3％,两组间的差异有显著性意义(P>0.05);两组流产成功者用药至胎儿排出时间分别为57.69±7.85小时和46.92±10.06小时,两组间的差异有显著性意义(P<0.01);两组流产成功者产程分别为8.09±6.97小时和11.4±8.28小时,双米组产程时间明显短于利凡诺组,P>0.001;流产后阴道流血量和阴道流血时间两组间差异无显著性意义(P>0.05);双米组胃肠道反应和头痛、眩晕等副反应发生率高于利凡诺组(P<0.05),但无需处理。结论:口服米非司酮200mg合并阴道放置米索前列醇是较好的药物终止16～24周妊娠的方法,可以作为一种常规方法在有条件的医院中应用。     

Comparison of gemeprost and vaginal misoprostol in first trimester mifepristone-induced abortion

BACKGROUND: The aim of this study was to compare efficacy and side effects of gemeprost and vaginal misoprostol in mifepristone-induced abortions in women up to 63 days of gestation. METHODS: A retrospective study of 833 consecutive patients admitted for medical termination of first trimester pregnancy was conducted. Four-hundred ten patients received mifepristone 600 mg, followed 48 h later by gemeprost 1 mg (regimen I), and 423 patients received mifepristone 200 mg followed by vaginal misoprostol 800 microg (regimen II). Success rates were evaluated after 2 weeks and after 3 months. The severity of bleeding and side effects (pain, nausea, vomiting and diarrhea) was scored by the patients, and requests for supplementary analgesic treatment were recorded by the attending nurse. RESULTS: Success rates were 99% in both groups after 2 weeks of follow-up. At 3 months of follow-up, success rates had declined to 94% for regimen I and 96% for regimen II. The frequency of severe pain was higher in regimen I compared to regimen II (72% vs. 60%, p < .001), but the severity of bleeding and gastrointestinal side effects was similar in the two regimens. CONCLUSION: When combined with mifepristone, gemeprost and vaginal misoprostol are equally effective for termination of first trimester abortion, but may be associated with varying intensity of side effects.     

Timing and efficacy of mifepristone pretreatment for medical management of early pregnancy loss

ObjectivesTo determine the time interval between mifepristone and misoprostol administration associated with the most efficacious early pregnancy loss (EPL) management.Study DesignWe performed a secondary analysis of a randomized trial. Participants with EPL were instructed to take 200 mg oral mifepristone followed by 800 mcg vaginal misoprostol 24 hours later. The primary outcome was gestational sac expulsion at the first follow-up visit (1–4 days after misoprostol use) after a single dose of misoprostol and no additional intervention within 30 days after treatment. Despite specification of drug timing, participants used the medication over a range of time. We graphed sliding average estimates of success and assessed the proportion of treatment successes over time to define timing interval cohorts for analysis. We used multivariable generalized linear regression to assess the association between time interval and success.ResultsOf 139 eligible participants, 70 (50.4%) self-administered misoprostol before 24 hours, and 69 (49.6%) at or after 24 hours. We defined the following time intervals: 0 to 6 hours (n = 22); 7 to 20 hours (n = 29); and 21 to 48 hours (n = 88). Success occurred in 96.6% of the 7- to 20-hour cohort compared to 54.6% and 87.5% of the cohorts self-administering misoprostol earlier or later, respectively. When adjusting for race, gestational age, diagnosis, bleeding at presentation, insurance status, and enrollment site, participants administering misoprostol between 0 and 6 hours (adjusted risk ratio 0.58, 95% CI 0.40–0.85) and 21 to 48 hours (adjusted risk ratio 0.91, 95% CI 0.72–0.99) had a lower risk of success when compared to participants administering 7 to 20 hours after mifepristone.ConclusionsThese data suggest that medical management of EPL has the highest likelihood of success when misoprostol is self-administered 7 to 20 hours after mifepristone.ImplicationsThese preliminary data suggest that patients have the highest likelihood of success when misoprostol is taken between 7 and 20 hours after mifepristone. In contrast with medical abortion, simultaneous medication administration may not be as effective as delayed. Future research is needed to confirm the optimal medication time interval.     

Feasibility of telephone follow-up after medical abortion

Background

This study was conducted to assess the feasibility of using telephone calls combined with high-sensitivity urine pregnancy testing as a primary method of follow-up after medical abortion.

Methods

We enrolled 139 women up to 63 days of gestation to receive mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, per their choice. Participants were contacted by phone one week after mifepristone administration and interviewed using standardized questions. If the subject or clinician thought the pregnancy was not expelled, the subject returned for an ultrasound examination. Otherwise, subjects performed high-sensitivity home urine pregnancy testing 30 days after the mifepristone and were called within 3 days of the test. Those with positive pregnancy tests returned for an ultrasound examination. Those with negative tests required no further follow-up.

Results

Six of the 139 (4.3%, 95% CI 1.6-9.1%) subjects presented prior to Phone Call 1 for an in-person visit. All 133 (100%, 95% CI 97.8-100%) subjects eligible for their first telephone follow-up were contacted. Eight of the 133 (6.1%, 95% CI 2.6-11.5%) women were asked to return for evaluation and all did so (100%, 95% CI 63.1-100%). Eight of the 133 women eligible for the 30 day phone call presented for an interim visit prior to the call. After 30 days, 116 of the 117 (99.1%, 95% CI 97.5-100%) eligible subjects were contacted. One subject was not reached for the day 30 phone call. Twenty-seven of the 116 (23.3%, 95% CI 15.6-31.0%) subjects had a positive pregnancy test and required follow-up. Two of these subjects (7.4%, 95% CI 1.0-24.2%) did not return for in-person follow-up. Two of the 116 (1.7%, 95% CI 0.2-6.1%) subjects had inconclusive pregnancy tests and were asked to return for follow-up. One of these subjects (50%, 95% CI 1.2-98.7%) did not return. Complete follow-up was achieved in 135 of the 139 subjects (97.1%, 95% CI 94.3-99.9%). None of the 26 women evaluated for a positive or inconclusive pregnancy test had a gestational sac or continuing pregnancy.

Conclusion

Telephone follow-up combined with urine pregnancy testing after medical abortion is a feasible alternative to routine ultrasonography or serial serum hCG measurements.     

Methotrexate and misoprostol for early abortion: A multicenter trial. I. Safety and efficacy

A prospective trial was conducted including 300 pregant women seeking elective abortion to evaluate the safety and efficacy of methotrexate and misoprostol for abortion at ≤56 days gestation. Subjects received methotrexate 50 mg/m² intramuscularly followed 7 days later by misoprostol 800 μg vaginally. The misoprostol dose was repeated the next day if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), duration of vaginal bleeding, and side effects. Complete abortion occurred in 263/300 (87.7%, 95% CI 83.4, 91.2%) patients. The complete abortion rate was higher for early gestations: 183/202 (90.6%, 95% CI 85.7, 94.2%) at ≤49 days gestation, and 80/98 (81.6%, 95% CI 72.5, 88.7%) from 50–56 days gestation (p=0.038). Abortion occurred in the 24 hours following the initial or repeat misoprostol dose (immediate success) in 65.0%; the remaining 22.7% of women who aborted did so after a delay of 23.6 ± 9.1 (mean ± standard deviation) days. Vaginal bleeding lasted 14 ± 7 days and 11 ± 9 days in immediate success and delayed success patients, respectively. Overall, 69.7%, 87.7%, and 91.7% of patients had passed the pregnancy by 14, 28, and 35 days, respectively, after receiving methotrexate. Methotrexate and misoprostol side effects were minimal. This treatment regimen offers an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.