Mifepristone pretreatment followed by misoprostol 200 mcg buccal for the medical management of intrauterine fetal death at 14-28 weeks: A randomized, placebo-controlled, double blind trial.

OBJECTIVE: To evaluate whether fetal and placental expulsion is more likely within 48 h if women receive mifepristone pre-treatment vs placebo pre-treatment followed by misoprostol 200 mcg buccally for treatment of fetal death at 14 weeks 0 days to 28 weeks and 6 days gestation. STUDY DESIGN: We randomized 176 women with a confirmed fetal death between 14 weeks and 0 days to 28 weeks and 6 days to mifepristone 200 mg or placebo; 24 h later all participants received misoprostol 200 mcg buccally every 3 h for up to 16 doses or 48 h. The trial took place in Hanoi, Vietnam and Mexico City in 2015-2018. RESULTS: Complete expulsion of the fetus and placenta within 48 h of misoprostol administration occurred in 74 of 90 women (82.2%, 95% confidence interval (CI), 72.7%-89.5%) in the mifepristone-misoprostol group and in 70 of 86 women (81.4%, 95% CI, 71.6%-89.0%) in the placebo-misoprostol group (Relative Risk (RR) 1.01, 95%CI 0.87-1.16, p = 0.887). The median time from the start of the misoprostol induction to fetal expulsion was shorter among women who received mifepristone-misoprostol compared to women assigned to placebo-misoprostol (7 h vs ±5 vs 12 ± 13 h; p < 0.001). Women in the mifepristone-misoprostol group were more likely to expel the fetus within 24 h of the start of misoprostol administration (96% vs 78%; RR 1.22 (1.09-1.39) p = 0.009). CONCLUSION(S): Mifepristone-misoprostol did not result in a higher rate of complete expulsion of the fetus and the placenta within 48 h of the start of misoprostol administration without any additional surgical intervention or medication (e.g. additional misoprostol doses or oxytocin) than placebo-misoprostol. However, treatment with mifepristone-misoprostol did result in a shorter time to expulsion than placebo misoprostol. IMPLICATIONS: Pretreatment with mifepristone followed by misoprostol bucally resulted in a shorter treatment time for medical management of fetal death than treatment with misoprostol alone. Pre-treatment with mifepristone may be more acceptable to women and providers by both reducing the length of hospital stay and the amount of misoprostol required.

A double-blind, randomized controlled trial to explore oral tranexamic acid as adjunct for the treatment for postpartum hemorrhage.

BACKGROUND: Oral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery. METHODS: From October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded. RESULTS: Of the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups. CONCLUSION: Adjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.

A non-inferiority study of outpatient mifepristone-misoprostol medical abortion at 64-70 days and 71-77 days of gestation.

OBJECTIVES: This open-label non-inferiority study assessed efficacy of a common outpatient medical abortion regimen among people with pregnancies 64-70 days and 71-77 days of gestation. STUDY DESIGN: We defined non-inferiority by a 6% margin of method success. People with intrauterine pregnancies 64-77 days' gestational age by abdominal ultrasound seeking medical abortion at one of eight clinics and met eligibility criteria were offered participation. Consenting participants took mifepristone 200 mg followed 24-48 h later by misoprostol 800 mcg buccally, and returned after one week for provider evaluation and abdominal ultrasound to determine abortion status. Participants recorded medication use, pregnancy expulsion, daily bleeding and pain scores until the one-week follow up. Clinic staff interviewed participants prior to study discharge to assess acceptability. RESULTS: Seven hundred and nineteen participants were enrolled, 393 and 326 in the respective groups. Successful expulsion without surgical intervention was achieved in 92.3% of the earlier gestational age group and 86.7% of the later group (difference in proportions 5.6%, 1-sided 95% CI 9.6). Ongoing pregnancy accounted for 3.6% and 8.7% (p = 0.007) of outcomes, respectively. Participants in the 71-77 day group reported nausea and weakness more frequently. Pain, bleeding and acceptability measures between groups were similar. CONCLUSION: Although the success rate at 71-77 days of gestation was within the non-inferiority margin, we cannot rule out that it is statistically worse than in the previous gestational week. Significantly more ongoing pregnancies in the later group raise concerns about using the regimen at 71-77 days.

Results of a pilot study in the U.S. and Vietnam to assess the utility and acceptability of a multi-level pregnancy test (MLPT) for home monitoring of hCG trends after assisted reproduction.

BACKGROUND: To evaluate the utility and acceptability of using multi-level pregnancy tests (MLPTs) at home to monitor hCG trends following assisted reproductive technology (ART). METHODS: One hundred and four women presenting for ART at either Stanford Medicine Fertility and Reproductive Health Clinic (Stanford, CA) or Hung Vuong Hospital (Ho Chi Minh City, Vietnam) participated in this pilot study. Women were asked to perform the MLPT at home, primarily on days when they were also scheduled to receive standard clinic-based serum hCG testing. These tests were administered up to 6 times over the 6-week period following embryo transfer or intrauterine insemination (IUI). Concordance of serial hCG readings for each time point was assessed by comparing trends in urine MLPT results with trends in serum hCG. Stable or increasing hCG level was interpreted as an indication of a progressing pregnancy, while a declining hCG was interpreted as a lack of established or progressing pregnancy. At study end, all participants were asked about the acceptability and convenience of using the MLPT at home for monitoring hCG trends following ART. RESULTS: Data from both urine and serum testing are available for 156 of 179 clinic visits (87.2%). There was high concordance of serial trend results between the two types of tests: among the 156 sets of serum and urine hCG data points, 150 (96.2%) showed a matching trend in hCG pattern and 6 (3.8%) resulted in a discordant trend. Seventy-three percent of women reported being satisfied or very satisfied with using the MLPTs at home. Almost all (96.6%) said that the MLPT was easy or very easy to use. CONCLUSION: The MLPT offers women and health care providers a client-friendly diagnostic tool to detect very early pregnancy and monitor its progress. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov as NCT01846403 (May 1, 2013), and NCT01919502 (August 5, 2013).

Serial multilevel urine pregnancy testing to assess medical abortion outcome: a meta-analysis.

OBJECTIVES: To summarize data on the accuracy of a strategy designed to exclude ongoing pregnancy after medical abortion treatment by observing a decline in urine human chorionic gonadotropin (hCG) concentration as estimated by multilevel urine pregnancy tests (MLPTs) performed before and after treatment. STUDY DESIGN: We collated original data from seven studies performed by our organization that evaluated the accuracy of the MLPT strategy for assessment of outcome of medical abortion. Our first analysis included data from the five studies in which each participant was evaluated both with the MLPT strategy and with ultrasound or other clinical assessment. Our second analysis combined data from two randomized trials that compared the MLPT strategy to assessment by ultrasound. Both analyses included only participants treated at ≤63 days of gestation. RESULTS: In the first analysis, 1482 (93%) of 1599 participants had a decline in hCG concentration after treatment. Twenty-one (1.3%) had an ongoing pregnancy, none of whom had a decline (predictive value 100%, 95% CI 93.3%, 100%). The remaining 96 women (6.0%) had no decline without an ongoing pregnancy. The second analysis, which included 3762 participants with follow-up, found no significant difference in the rates of ongoing pregnancy ascertained in the randomized groups (RR 0.88; 95% CI 0.50, 1.54). Nearly all of the post-treatment MLPTs in the seven studies (3484/3535; 99%) were performed by the participants themselves. CONCLUSIONS: Serial multilevel urine pregnancy testing is a highly reliable and efficient strategy for excluding ongoing pregnancy after medical abortion at≤63 days of gestation. IMPLICATIONS STATEMENT: Serial urine testing using MLPTs can obviate the need for routine ultrasound or examination after medical abortion treatment and can allow most women to avoid an in-person follow-up visit to the abortion facility.

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.

Buccal misoprostol for treatment of fetal death at 14-28 weeks of pregnancy: a double-blind randomized controlled trial.

OBJECTIVE: To assess whether buccal misoprostol is effective for the treatment of intrauterine fetal death. STUDY DESIGN: This double-blind randomized trial was conducted at five tertiary-level hospitals in the United States and Vietnam. One hundred fifty-three women with an intrauterine fetal death at 14-28 weeks of pregnancy received either 100 mcg buccal misoprostol or 200 mcg buccal misoprostol every 6 h for a maximum of 8 doses. The main outcome measure was the fetal-placental delivery rate within 48 hours of prostaglandin commencement without any additional intervention. RESULTS: Most of the women (140/153) were recruited at the study site in Vietnam. Expulsion of both fetus and placenta within 48 hours of prostaglandin commencement without any additional interventions occurred in 61.8% (47/76) of women receiving misoprostol 100 mcg and 77.9% (60/77) of women receiving misoprostol 200 mcg. The 200 mcg dose was significantly more effective than the 100 mcg dose at expelling the fetus and placenta within 48 h [RR 0.68 (95% CI: 0.50-0.92; p=.03)]. The mean time to expulsion was significantly shorter using the 200 mcg dose (18.5±11.9 h) than the 100 mcg dose (23.9±12.5 h) (p=.02). Most women in both groups found the procedure satisfactory or very satisfactory (100 mcg: 76.7% (56/73); 200 mcg: 89.5% (68/76) [RR 0.86 (95% CI: 0.74-1.00)]. CONCLUSION: Buccal misoprostol is an effective method for medical induction of labor after intrauterine fetal demise. A 200 mcg dose is significantly more effective than 100 mcg for evacuating the uterus within 48h. The treatment is highly acceptable to women. IMPLICATIONS: Administration of 200 mcg buccal misoprostol every six hours is an effective and acceptable method to effect the delivery of a demised fetus at 14-28 weeks that can be feasibly implemented in a wide variety of settings.

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.

Results from a study using misoprostol for management of incomplete abortion in Vietnamese hospitals: implications for task shifting.

BACKGROUND: Complications following spontaneous or induced abortion are a major cause of maternal morbidity. To manage these complications, post-abortion care (PAC) services should be readily available and easy to access. Standard PAC treatment includes surgical interventions that are highly effective but require surgical providers and medical centers that have the necessary space and equipment. Misoprostol has been shown to be an effective alternative to surgical evacuation and can be offered by lower level clinicians. This study sought to assess whether 400 mcg sublingual misoprostol could effectively evacuate the uterus after incomplete abortion and to confirm its applicability for use at lower level settings. METHODS: All women presenting with incomplete abortion at one of three hospitals in Vietnam were enrolled. Providers were not asked to record if the abortion was spontaneous or induced. It is likely that all were spontaneous given the legal status and easy access to abortion services in Vietnam. Participants were given 400 mcg sublingual misoprostol and instructed to hold the pills under their tongue for 30 minutes and then swallow any remaining fragments. They were then asked to return one week later to confirm their clinical status. Study clinicians were instructed to confirm a complete expulsion clinically. All women were asked to complete a questionnaire regarding satisfaction with the treatment. RESULTS: Three hundred and two women were enrolled between September 2009 and May 2010. Almost all participants (96.3%) had successful completions using a single dose of 400 mcg misoprostol. The majority of women (87.2%) found the side effects to be tolerable or easily tolerable. Most women (84.3%) were satisfied or very satisfied with the treatment they received; only one was dissatisfied (0.3%). Nine out of ten women would select this method again and recommend it to a friend (91.0% and 90.0%, respectively). CONCLUSIONS: This study confirms that 400 mcg sublingual misoprostol effectively evacuates the uterus for most women experiencing incomplete abortion. The high levels of satisfaction and side effect tolerability also attest to the ease of use of this method. From these data and given the international consensus around the effectiveness of misoprostol for incomplete abortion care, it seems timely that use of the drug for this indication be widely expanded both throughout Vietnam and wherever access to abortion care is limited. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00670761.

Simplified medical abortion using a semi-quantitative pregnancy test for home-based follow-up.

OBJECTIVE: To simplify follow-up after medical abortion by examining whether women could use a semi-quantitative pregnancy test at home to screen for ongoing pregnancy. METHODS: Three hundred women seeking medical abortion at a tertiary hospital in Vietnam participated in the study. Participants used a semi-quantitative pregnancy test at the hospital to estimate baseline human chorionic gonadotropin (hCG) levels and administered another test at home 2 weeks later for comparison. Women interpreted the test result at home and then returned to hospital for follow-up care. At this visit, self-assessment was verified. To assess further the feasibility of the test as a follow-up tool in service delivery, 200 additional women completed a user comprehension survey. RESULTS: The tests identified all 11 ongoing pregnancies among study participants (100% sensitivity; 89.7% specificity). Women reported that the test was easy to use (255/292 [87.3%]) and that provider instructions helped them to use the test (291/292 [99.7%]). CONCLUSION: Semi-quantitative pregnancy tests offer high sensitivity and negative predictive value. If user instructions can be further simplified, the tests could be used in lieu of transvaginal ultrasound and/or serum hCG at clinic-based follow-up or by women themselves for home-based follow-up. Clinical trials.gov:NCT01150279.

Clinic-level introduction of medical abortion in Vietnam.

OBJECTIVE: To assess the efficacy of medical abortion and patient satisfaction in the clinic setting, in addition to determining healthcare providers' views. METHODS: From 2006 to 2008, 2400 women were enrolled at 10 Vietnam Family Planning Association (VINAFPA) clinics in an operations research project. Participants took 200mg of oral mifepristone in the clinic and 400 µg of oral misoprostol 2 days later at home or in the clinic. Abortion status was assessed at follow-up. Furthermore, in 2006, 900 clinicians at 45 health facilities answered a knowledge, attitudes, and practices survey to capture providers' views. RESULTS: In total, 93.8% of participants had successful medical abortions. The majority (84.5%) administered misoprostol at home. Adverse effects included bleeding, pain/cramps, and nausea. Most women (92.6%) were satisfied/very satisfied with the method. Most providers who took the survey (85.6%) recommended that medical abortion be introduced at VINAFPA clinics. CONCLUSION: The operations research data demonstrate the safety, efficacy, and acceptability of medical abortion at VINAFPA clinics. The majority of surveyed providers endorsed adding medical abortion at their own facilities. Developing national guidelines for providing medical abortion at the clinic level is an important step in expanding access to services in Vietnam.

Comparison of misoprostol-only and combined mifepristone-misoprostol regimens for home-based early medical abortion in Tunisia and Vietnam.

OBJECTIVE: To assess the potential advantages of combined mifepristone-misoprostol versus misoprostol-only for early medical abortion. METHODS: A double-blind randomized placebo controlled study was conducted that enrolled 441 pregnant women (<63 days since last menstrual period) at 2 hospitals in Tunisia and Vietnam. The mifepristone-misoprostol group (n=220) received 200mg of mifepristone on day 1 and 800 µg buccal misoprostol followed by placebo 3 hours later on day 2. The misoprostol-only group (n=221) received placebo on day 1 and 1600 µg of misoprostol (2 doses of 800 µg, given 3 hours apart) on day 2. All medications were self-administered at home with follow-up 1 week later. The primary outcome was complete uterine evacuation without surgical intervention. RESULTS: Successful uterine evacuation occurred for 78.0% (n=170) of women with misoprostol only versus 92.9% (n=195) of women with mifepristone-misoprostol (relative risk 0.84, 95% CI, 0.78-0.91; P<0.001). Ongoing pregnancy occurred for 13.8% (n=30) of women given misoprostol-only and 1.4% (n=3) of women given mifepristone-misoprostol (relative risk 9.63, 95% CI 2.98-31.09; P<0.001). CONCLUSION: Mifepristone plus misoprostol is significantly more effective than misoprostol-only for early medical abortion.

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.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial.

BACKGROUND: Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin. METHODS: In this double-blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 mug misoprostol (n=407) or 40 IU intravenous oxytocin (n=402). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS: All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95-1.04; crude difference 0.4%, 95% CI -3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09-1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died. INTERPRETATION: Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour.

Mifepristone followed in 24 hours to 48 hours by misoprostol for late first-trimester abortion.

OBJECTIVE: To investigate the efficacy of mifepristone and misoprostol for the termination of pregnancies in the late first trimester. METHODS: This was a prospective study of 321 women seeking termination of pregnancy with gestations from 64 days to 84 days (+/-3 days) by vaginal ultrasonography. Women were enrolled at three sites: University of Rochester Reproductive Health Program in Rochester, New York; Hung Vuong Hospital in Ho Chi Minh City, Vietnam; and K.E.M. Hospital in Pune, India. Eligible women received 800 mcg of misoprostol vaginally between 24 hours and 48 hours after administration of 200 mg mifepristone. Two additional doses of 400 mcg of misoprostol were administered either orally or vaginally as needed every 3 hours for a maximum of two additional doses (total 1,600 mcg). The primary study outcome measure was complete abortion without surgical intervention. RESULTS: Eighty-nine percent of women who completed the study successfully terminated their pregnancies. Most women were either satisfied (64.8%) or very satisfied (28.6%) with their experience. Ninety-four percent of women reported that they would recommend the procedure to a friend. Most women (90.4%) also agreed they would request a medical abortion if they required another abortion at this gestational age. CONCLUSION: Medical abortion is acceptable and effective in the late first trimester and offers women an acceptable alternative to surgical abortion. LEVEL OF EVIDENCE: II.

Accounting for time: insights from a life-table analysis of the efficacy of medical abortion.

OBJECTIVE: Previously published analyses have ignored the temporal nature of medical abortion and calculated effectiveness as the proportion of abortions that succeed. By using life tables, we incorporate the important element of time to produce unbiased efficacy rates as well as afford insight into the medical abortion process. STUDY DESIGN: Using data on 6568 women from 6 previously published mifepristone-misoprostol medical abortion studies, we generated multidecrement life table efficacy curves and evaluated the cumulative probability of successful medical abortion. RESULTS: Efficacy rates calculated using proportions are biased because of loss to follow-up. Compliance with the medical abortion regimen was high. More than 80% of abortions were complete within a week of receiving mifepristone. Success continued to improve thereafter. Most surgical interventions were unnecessary. CONCLUSION: Follow-up visits can be scheduled within a week of receiving mifepristone; however, aspirations should not be performed routinely if the abortion is not complete.

Is home-based administration of prostaglandin safe and feasible for medical abortion? Results from a multisite study in Vietnam.

OBJECTIVES: To study the efficacy and acceptability of a simplified medical abortion regimen in Vietnam. DESIGN: Open-label study. SETTING: One peri-urban and three urban hospitals and four urban maternal-child health family planning clinics located in Northern, Central and Southern Vietnam. SAMPLE: A total of 1601 women seeking abortion services from January 2001 to December 2001. METHODS: Consenting women presenting for abortion services with gestations less than 56 days LMP who met the inclusion criteria were given 200 mg mifepristone and offered the choice of either home or clinic administration of 400 microg oral misoprostol two days later. MAIN OUTCOME MEASURE: Complete abortion rate of 89.2% (n= 1395), with 1.5% (n= 24) of the women lost to follow up. The majority of women (>90%) reported that their medical abortion experience was either 'very satisfactory' or 'satisfactory'. RESULTS: There was a strong preference for home administration of misoprostol, with more than four-fifths of the study population selecting to administer the prostaglandin at home. Location of misoprostol administration did not affect efficacy rate. Regardless of location selected, women expressed a high degree of satisfaction with the medical abortion experience. CONCLUSIONS: Medical abortion with the option of home administration of misoprostol is safe and feasible for introduction into the Vietnamese healthcare system.

Differences in efficacy, differences in providers: results from a hazard analysis of medical abortion.

Sample sizes of even the largest medical abortion trials are generally not adequate to provide an understanding of how well the regimen works for subgroups of women, particularly when controlling for factors known to influence efficacy, such as gestational age. By pooling data from four previously published studies of medical abortion and using hazard analyses, we can undertake such an investigation. We find that women with lower gestational ages, women younger than 23 years of age, women with more than 12 years of education and women with no previous induced abortion experience were more likely to experience a successful medical abortion. After taking into account demographic factors, we find that significant differences in efficacy persist across study sites, indicating that differences in providers' tendency to intervene by performing vacuum aspiration vary across medical abortion providers.