Simultaneous Administration Compared With a 24-Hour Mifepristone-Misoprostol Interval in Second-Trimester Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare outcomes with simultaneous administration of mifepristone and misoprostol with a regimen in which the drugs are administered at a 24-hour interval for second-trimester abortion. METHODS: In this placebo-controlled, double-blind trial, participants were randomized to receive mifepristone either 24 hours before or at the same time as misoprostol. Participants were hospitalized to receive 400 micrograms buccal misoprostol at 3-hour intervals up to 48 hours or until uterine expulsion. The primary outcome was the proportion of women who experienced uterine expulsion within 24 hours after the first misoprostol dose and this required 504 women to examine our hypothesis that this rate would be 85% in the 24-hour interval arm compared with 70% in the simultaneous arm. Secondary outcomes included total abortion time from mifepristone and misoprostol. RESULTS: From February 2013 to April 2014, 509 women were enrolled. Women in the 24-hour interval arm were more likely to abort within 24 hours (94.4% compared with 85.0%, relative risk 1.11, 95% confidence interval [CI] 1.05-1.18). At 48 hours, the rate was similar in the two arms (96.8% [24-hour interval] and 95.7% [simultaneous], relative risk 1.01, 95% CI 0.97-1.04). Median misoprostol dosing time was shorter in the 24-hour interval arm (7.7 compared with 13 hours; P<.001) and consistent with the median misoprostol doses required (three compared with five; P<.001). Median time from mifepristone to uterine expulsion was longer in the 24-hour interval arm (32.3 compared with 13 hours; P<.001). Both regimens had high acceptability rates and reported similar side effects and pain scores. CONCLUSION: Administering mifepristone and misoprostol simultaneously results in lower expulsion rates within 24 hours of taking misoprostol, longer median misoprostol treatment times, and requires more misoprostol doses. At 48 hours, both regimens work equally well. Simultaneous dosing results in less total time from the first clinical contact to complete abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01768299.

Randomized trial assessing home use of two pregnancy tests for determining early medical abortion outcomes at 3, 7 and 14days after mifepristone.

OBJECTIVE: To evaluate the accuracy, feasibility and acceptability of two urine pregnancy tests in assessing abortion outcomes at three time points after mifepristone administration. STUDY DESIGN: This randomized trial enrolled women seeking early medical abortion at two hospitals in Vietnam. Investigators randomly allocated participants to at-home administration of a multilevel urine pregnancy test (MLPT) or a high sensitivity urine pregnancy test (HSPT) to assess their abortion outcomes. A baseline test was administered on the same day as mifepristone. Participants performed and interpreted results of pregnancy tests taken 3, 7 and 14days after mifepristone. Ultrasound exam determined continuing pregnancy. RESULTS: Six hundred women enrolled, and 300 received each test. A percentage of 97.4 (584) had follow-up, of whom 13 women had continuing pregnancies. The specificity of MLPT at detecting absence of continuing pregnancy was 63.9%, 90.4% and 97.1% at study day 3, 7 and 14. The specificity of HSPT was 6.0%, 19.8% and 62.2%, respectively. The positive predictive value (PPV) of MLPT at detecting continuing pregnancy was 6.4% at day 3 and rose to 46.7% at day 14. In contrast, the PPV for HSPT was 2.2% at day 3 and rose to 6.5% at day 14. At all three time points, the sensitivity and negative predictive values for both tests were 100.0%. Most women found their assigned tests easy to use and would prefer future home follow-up with a pregnancy test. CONCLUSIONS: The MLPT enables women to assess their abortion outcomes more reliably than with HSPT. With MLPT, women can know their outcomes as early as 3 days after mifepristone. IMPLICATIONS: Medical abortion service delivery with an MLPT to obtain a baseline (preabortion) human chorionic gonadotropin (hCG) estimate and a second follow-up MLPT 1 to 2 weeks later can establish whether there has been a drop in hCG, signifying absence of a continuing pregnancy. Used this way, MLPTs can enable women to assess their abortion status outside of a clinic setting and without serum hCG testing and/or ultrasound.

Acceptability and feasibility of phone follow-up after early medical abortion in Vietnam: a randomized controlled trial.

OBJECTIVE: To investigate phone follow-up with a semiquantitative urine pregnancy test and symptom checklist as a replacement for universal clinic follow-up after medical abortion. METHODS: One thousand four hundred thirty-three women seeking early medical abortion at four hospitals in Vietnam were randomized to clinic or phone follow-up. Women allocated to clinic follow-up returned to the hospital for confirmation of abortion outcome 2 weeks after mifepristone administration. Women assigned to phone follow-up completed a semiquantitative pregnancy test at initial visit to determine baseline human chorionic gonadotropin range and again at home 2 weeks later. Clinic staff called women to review the pregnancy test results and symptom checklist. Women who screened positive were referred to the clinic. Effectiveness, feasibility, and acceptability of the follow-up methods were assessed. RESULTS: The rate of ongoing pregnancy was not significantly different between the two groups (clinic: 2.7% phone, 2.5%, relative risk 0.9, 95% confidence interval 0.99-1.02). Eighty-five percent of women in the phone group did not need an additional clinic visit. Phone follow-up was highly effective in screening for ongoing pregnancy with a sensitivity and specificity of 92.8% and 90.6%, respectively. Specificity of the pregnancy test alone (eg, without the symptom checklist) was higher (95.7%). CONCLUSION: Phone follow-up offers a feasible and effective approach to identify women with ongoing pregnancy after early medical abortion. When used with the semiquantitative pregnancy test, the symptom checklist offered no additional benefit and decreased the specificity of the screening. Given its effectiveness and ease of use, the semiquantitative pregnancy test alone could replace routine clinic follow-up after early medical abortion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01150422. LEVEL OF EVIDENCE: I.

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial.

OBJECTIVE: To estimate the clinical benefit of pretreatment with mifepristone followed by misoprostol compared with misoprostol alone for second-trimester abortion. METHODS: Two hundred sixty women with live fetuses of gestational ages 14-21 weeks were enrolled in a randomized, placebo-controlled, double-blind trial in Vietnam. Eligible consenting women received either mifepristone or placebo to take on their own at home and were scheduled to return to the hospital the next day. At the hospital, women were given 400 micrograms buccal misoprostol every 3 hours, up to five doses, until both the fetus and placenta were expelled. Efficacy was evaluated 15 hours after misoprostol dosing began and the procedure was considered complete if uterine evacuation was achieved without recourse to surgical evacuation. RESULTS: Pretreatment with mifepristone resulted in more than twice the chance of complete uterine evacuation in 15 hours (79.8% compared with 36.9%, relative risk 2.16, 95% confidence interval 1.70-2.75). The mean induction-to-abortion interval for complete uterine evacuations was statistically significantly shorter among participants pretreated with mifepristone compared with those given misoprostol alone (8.1, standard deviation 2.8, range 2.5-14.8; and 10.6, standard deviation 2.5, range 6.5-15.5 hours, respectively; P<.001). The side-effect profiles for the two regimens did not differ significantly and acceptability of the treatments was high. CONCLUSION: Mifepristone-misoprostol is more efficacious and faster than misoprostol alone. Services offering home administration of mifepristone as pretreatment could optimize efficacy and acceptability of medical abortions for women with gestations 14-21 weeks since the last menstrual period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00784186. LEVEL OF EVIDENCE: I.

Comparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone.

BACKGROUND: Nonsurgical abortion methods have the potential to improve access to high-quality abortion care. Until recently, availability and utilization of mifepristone medical abortion in low-resource countries were restricted due to the limited availability and perceived high cost of mifepristone, leading some providers and policymakers to support use of misoprostol-only regimens. Yet, this may not be desirable if misoprostol-only regimens are considerably less effective and ultimately more costly for health care systems. This study sought to document the differences in efficacy between two nonsurgical abortion regimens. STUDY DESIGN: This double-blind randomized placebo-controlled trial enrolled women with gestational ages up to 63 days seeking early medical abortion from August 2007 to March 2008 at a large tertiary hospital in Ho Chi Minh City, Vietnam. Eligible consenting women received either (1) two doses of 800 mcg buccal misoprostol 24 h apart or (2) 200 mg mifepristone and 800 mcg buccal misoprostol 24 h later. Participants self-administered all study drugs and returned to the hospital for follow-up 1 week later. The trial is registered at ClinicalTrials.gov as NCT00680394. RESULTS: Four hundred women were randomized to either misoprostol-only (198) or mifepristone+misoprostol (202). Complete abortion occurred for 76.2% (n=147) of women allocated to misoprostol-only vs. 96.5% (n=194) of those given mifepristone+misoprostol (RR 0.79, 95% CI 0.73-0.86). Ongoing pregnancy was documented for 16.6% (32) of misoprostol-only users and 1.5% (3) of mifepristone+misoprostol users (1.62, 0.68-3.90). Side effects were generally similar for both groups, although significantly more women allocated to misoprostol-only reported diarrhea. CONCLUSIONS: Mifepristone+misoprostol is significantly more effective than use of misoprostol-alone for early medical abortion. The number of ongoing pregnancies documented with misoprostol-only warranted an early end of the trial after unblinding of the study at interim analysis. Policymakers should advocate for greater access to mifepristone. Future research should prioritize misoprostol-only regimens with shorter dosing intervals.