A double-blind randomized controlled trial of mifepristone or placebo before buccal misoprostol for abortion at 14-21 weeks of pregnancy.

OBJECTIVE: To assess differences in outcomes of misoprostol with or without mifepristone for second-trimester abortion. METHODS: A randomized, double-blind, placebo-controlled trial of buccal misoprostol following placebo or 200mg mifepristone was done in Tunisia among women presenting for abortions at 14-21 weeks of pregnancy between August 2009 and December 2011. Women with a live fetus, a closed cervical os, no cervical bleeding, and no contraindications to study drugs were eligible and underwent randomization (block size 10). Participants returned 24 hours later to receive 400 µg buccal misoprostol every 3 hours until complete fetal and placental expulsion (maximum 10 doses, five per 24-hour period). The primary outcomes were rates of complete uterine evacuation at 48 hours and time to expulsion. RESULTS: A total of 120 women were evenly randomized to treatment. Complete uterine evacuation at 48 hours was recorded in 55 (91.7%) women in the combined group versus 43 (71.7%) in the misoprostol alone group (relative risk 1.28; 95% confidence interval 1.07-1.53). Mean time to complete abortion was 10.4±6.6 hours in the group who received mifepristone versus 20.6±9.7 hours in the misoprostol alone group (P<0.001). Side effects were similar in both groups. CONCLUSION: Adding mifepristone before misoprostol can improve the quality of second-trimester abortion care by making the process faster.

Acceptability and feasibility of mifepristone-misoprostol for menstrual regulation in Bangladesh.

CONTEXT: Annually, more than 700,000 women turn to menstrual regulation, or uterine evacuation with vacuum aspiration; many more resort to unsafe abortion. Using pills for the evacuation of the uterus could increase women's access to safe menstrual regulation services and reduce the high levels of abortion- and menstrual regulation- related morbidity in Bangladesh. METHODS: At 10 facilities in Bangladesh, 651 consenting women who were seeking menstrual regulation services and who were 63 days or less past their last menstrual period received 200 mg of mifepristone followed 24 hours later by 800 mcg of buccal misoprostol, administered either at home or in the clinic. Prospective data were collected to determine women's experience and satisfaction with the procedure, menstrual regulation outcome, and the human and physical resources required for providing the method. Focus group discussions were conducted with a purposively sampled group of service providers at each site to understand their attitudes about the introduction of menstrual regulation with medication. RESULTS: The majority of women (93%) with known menstrual regulation outcomes evacuated the uterus without surgical intervention. Overall, most women (92%) were satisfied with use of pills for their menstrual regulation. Providers faced initial challenges and concerns, particularly related to the additional counseling requirements and lack of control over the final outcome, but became more confident after successful use of the medication regimen. CONCLUSIONS: Mifepristone-misoprostol can be safely offered within existing menstrual regulation services in urban and periurban areas in Bangladesh and is highly acceptable to women. Providers' initial concerns diminish with increased experience with the method.

Efficacy and acceptability of early mifepristone-misoprostol medical abortion in Ukraine: results of two clinical trials.

BACKGROUND: Abortion services are legally available in Ukraine although there are issues in quality and access. Two studies were conducted in Ukraine to expand options for women, and to determine the efficacy and acceptability of medical abortion. STUDY DESIGN: Two open-label clinical trials were conducted at six clinics in Ukraine. Women were given 200 mg mifepristone followed after 48 hours by 400 µg oral misoprostol (Study One) and mifepristone followed after 24 hours by 400 µg sublingual misoprostol (Study Two). Follow-up visits were scheduled for two weeks after mifepristone administration to assess whether complete uterine evacuation had occurred. RESULTS: Success rates were 97% in the first study and 98% in the second one. The vast majority of participants were satisfied or very satisfied with their abortion method (Study One: 94%; Study Two: 98%). CONCLUSIONS: The two studies demonstrate high rates of success and acceptability of early medical abortion in Ukraine.

Acceptability and feasibility of the use of 400 µg of sublingual misoprostol after mifepristone for medical abortion up to 63 days since the last menstrual period: evidence from Uzbekistan.

OBJECTIVE: To examine the efficacy, acceptability and feasibility of early medical abortion, with the option of home administration of misoprostol, in Uzbekistan. METHODS: A total of 450 women were enrolled at national, municipal and private facilities in Tashkent, Uzbekistan. Women who presented for termination of pregnancy with gestations up to 63 days were recruited to participate in the study. All eligible pregnant women who consented to participate swallowed a 200 mg mifepristone pill in the clinic and were given the option of taking 400 µg misoprostol sublingually either at the clinic or at home 24-48 hours after mifepristone administration. Abortion status was determined two weeks later. RESULTS: Almost all women (99.5%) chose home administration of misoprostol. The sublingual route of misoprostol administration was acceptable or very acceptable to 89% of participants. Ninety-five percent of women had complete abortions after mifepristone and misoprostol. Almost all participants preferred a medical abortion to surgery for a future procedure (95%). CONCLUSIONS: Mifepristone medical abortion with home administration of misoprostol is an acceptable and feasible option for women in Uzbekistan. The method worked well at all three facility types.

Misoprostol for the management of postpartum bleeding: a new approach.

Excessive postpartum hemorrhage (PPH) is a leading cause of maternal death globally. Current approaches to address PPH at the community level focus on reducing the incidence of PPH, but often fail to address the issue of PPH treatment. Given that institutional delivery is not yet a reality for all women, comprehensive care for excessive bleeding after delivery needs to be available at the community level. A new hybrid model of "secondary prevention"-presumptive treatment for women with more than average blood loss-presents one alternative community-based approach. If shown to be effective and feasible, this approach could support policy changes and avoid the need to provide uterotonics to all women after delivery. This Special Communication discusses some of the benefits and limitations of current community approaches using misoprostol for PPH prevention and explains why it is now opportune to translate clinical knowledge into pragmatic PPH service delivery strategies.

Misoprostol for prevention and treatment of postpartum hemorrhage: what do we know? What is next?

Misoprostol is an effective and safe uterotonic for the prevention and treatment of postpartum hemorrhage (PPH). A 600-µg oral dose of misoprostol has been shown to prevent PPH in community-based randomized controlled trials. An 800-µg sublingual dose of misoprostol appears to be a good first-line treatment for controlling PPH. Adverse effects after use of misoprostol for PPH prevention or treatment may include shivering and fever. These effects are transient, resolve on their own, and are not life threatening. Misoprostol can play an important role in settings with limited access to oxytocin, and where there is no other option for PPH care.

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.

Comparison of 400 mcg buccal and 400 mcg sublingual misoprostol after mifepristone medical abortion through 63 days' LMP: a randomized controlled trial.

BACKGROUND: Buccal misoprostol 800 mcg and sublingual misoprostol 400 mcg demonstrate high efficacy and few adverse effects when used with 200 mg mifepristone for medical abortion through 63 days since the last menstrual period (LMP). Little is known about a 400-mcg buccal dose. This study compares two in-the-mouth routes of misoprostol using the same dose. STUDY DESIGN: Eligible and consenting women (n=550) were randomized to 400 mcg of misoprostol buccally or sublingually 24 h after ingestion of 200 mg of mifepristone. Abortion status was assessed 2 weeks later. RESULTS: Complete abortion occurred in 97.1% of the buccal group and 97.4% of the sublingual group (p=.97, RR: 1.00, 95% CI=0.97-1.03). Adverse effects were similar in both groups. Over 90% of women in both arms expressed high satisfaction with the method. CONCLUSIONS: Both 400 mcg buccal misoprostol and 400 mcg sublingual misoprostol after mifepristone appear to be good options for medical abortion through 63 days' LMP.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial.

BACKGROUND: Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-partum haemorrhage in women not exposed to oxytocin during labour. METHODS: In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 microg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). 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 with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95% CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25-3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died. INTERPRETATION: In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.

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.

Two routes of administration for misoprostol in the treatment of incomplete abortion: a randomized clinical trial.

BACKGROUND: This study was conducted to compare the safety, effectiveness and acceptability of 400 mcg sublingual misoprostol and 600 mcg oral misoprostol for treatment of incomplete abortion. STUDY DESIGN: We used an open-label randomized controlled trial conducted from July 2005 to August 2006 in a large tertiary level maternity hospital in Antananarivo, Madagascar, and a large tertiary level hospital in Chisinau, Moldova. Three hundred consenting women seeking treatment for clinically diagnosed incomplete abortion with uterine size

Two-pill regimens of misoprostol after mifepristone medical abortion through 63 days' gestational age: a randomized controlled trial of sublingual and oral misoprostol.

BACKGROUND: A 400 mcg dose of sublingual misoprostol has high efficacy and few side effects when used with 200 mg mifepristone for medical abortion through 63 days' gestation. STUDY DESIGN: Eligible and consenting women (n=480) were randomized to 400 mcg of misoprostol sublingually or orally, 24 h after 200 mg of mifepristone. Abortion status was assessed two weeks later. RESULTS: Complete abortion occurred in 98.7% of the sublingual group and 94.0% of the oral group (p value=.006, RR: 1.05, 95% CI=1.01--1.09). Over 90% of women in both arms expressed high satisfaction with the method. Side effects were similar in both groups, with only fever or chills reported by significantly more women in the sublingual arm. CONCLUSIONS: The sublingual route appears superior to the regimen of 400 mcg misoprostol used orally and may be a good option for mifepristone medical abortion.