Rasha Dabash

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.

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.

A randomized controlled trial of 400‐μg sublingual misoprostol versus manual vacuum aspiration for the treatment of incomplete abortion in two Egyptian hospitals

To compare the safety, efficacy, and acceptability of 400‐μg sublingual misoprostol with that of manual vacuum aspiration (MVA) in 2 Egyptian hospitals.

Increasing women's choices in medical abortion: A study of misoprostol 400 μg swallowed immediately or held sublingually following 200 mg mifepristone

Objectives To assess the efficacy and acceptability of two misoprostol regimens (400 μg oral or sublingual) following mifepristone for medical abortion. Methods Women seeking abortion with gestations of 56 days or less since onset of their last menstrual period were offered medical abortion as an alternative to a surgical procedure. A total of 207 eligible and consenting women were given mifepristone (200 mg oral) and the option of taking 400 μg misoprostol either orally or sublingually two days later, with the option of home-use. Two weeks later, treatment success, satisfaction, and the frequency and acceptability of side effects were assessed. Results Most women (97.6%) opted for home use of misoprostol and almost three quarters selected the oral route. Overall efficacy, acceptability of side effects and satisfaction were high in both groups. The success rate was lower after sublingual than after oral administration but not significantly so (91.3% vs. 96.3%, p = 0.23, RR: 0.93, 95% CI = 0.85–1.02). The frequency and average duration of side effects in both groups were comparable except for pain/cramps and fever/chills, which were more frequently associated with the sublingual route. Conclusions This study re-emphasises the feasibility of integrating medical abortion into health services in Turkey and the potential to increase choices for women.

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

To assess the potential advantages of combined mifepristone–misoprostol versus misoprostol‐only for early medical abortion.

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

To assess differences in outcomes of misoprostol with or without mifepristone for second‐trimester abortion.

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.

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.

Self-administered multi-level pregnancy tests in simplified follow-up of medical abortion in Tunisia.

BackgroundThis study was conducted to assess the efficacy and acceptability of using a multi-level pregnancy test (MLPT) combined with telephone follow-up for medical abortion in Tunisia, where the majority of providers are midwives.MethodsFour hundred and four women with gestational age ≤ 70 days’ LMP seeking medical abortion at six study sites were enrolled in this open-label trial. Participants administered a baseline MLPT at the clinic prior to mifepristone administration and were asked to take a second MLPT at home and to call in its results before returning the day of their scheduled follow-up visit 10-14 days later.ResultsAlmost all women with follow-up (97.1 %, n = 332/342) had successful abortions without the need for surgical intervention. The MLPT worked extremely well among women ≤63 days’ LMP in ruling out ongoing pregnancy (negative predictive value (NPV) =100 % (n = 298/298)) and also detecting women with ongoing pregnancies (sensitivity = 100 %; 2/2) as needing follow-up due to non-declining hCG. Among women 64-70 days’ LMP, the test also worked well in ruling out ongoing pregnancy (NPV = 96.9 % (n = 31/32) but not as well in terms of sensitivity (50 %), with only one of two ongoing pregnancies detected by MLPT as needing follow-up. Most women (95.1 %) found the MLPT to be very easy or easy to use and would consider using the MLPT again (97.4 %) if needed.ConclusionsSelf-administered pre and post MLPT are very easy for women to use and accurate in assessing medical abortion success up to 63 days’ LMP. MLPT use for medical abortion follow-up has the potential to facilitate task sharing services and eliminate the burden of routine in-person follow-up visits for the large majority of women. Additional research is warranted to explore the accuracy of the MLPT in identifying ongoing pregnancy among women with gestational ages > 63 days.Trial registrationThis study was registered on May 13, 2010, on clinicaltrials.gov as NCT01150279.