Domestication of the Maputo Protocol in the Democratic Republic of Congo: Leveraging regional human rights commitments for abortion decriminalization and access.

The Maputo Protocol, adopted over 20 years ago, is a promising regional treaty for advancing gender equity and sexual and reproductive health and rights. This instrument has driven progress in women's health and rights across Africa, with much remaining to achieve to realize its full potential for women and girls, including access to safe abortion. The present paper shares the strategies and lessons from the Democratic Republic of Congo's (DRC) reform centered on the domestication of the Protocol, specifically applying its commitments on abortion decriminalization and access. With a vision of addressing maternal mortality and rectifying the impacts of widespread sexual violence against women during war, abortion as a human right and health imperative was at the heart of the DRC's reform. Governmental commitment, broad coalition building, evidence generation, and an intersectional advocacy agenda were critical to overcoming opposition, stigma, and other challenges. This paper shares key learnings from the DRC's complex yet collaborative reform strategies and its processes. The strategy prioritized domestication of the Protocol for numerous reforms, including paving the path to legal abortion on the broad grounds of rape or incest, and saving women's health and/or life. With a commitment to maximizing quality, access, task sharing, and equity, progressive national comprehensive abortion guidelines were created alongside an implementation roadmap for accountability. The DRC's experience leveraging the Maputo Protocol's obligations to advance abortion rights and access offers valuable insights for consideration globally.

Adaptations to comprehensive abortion care during the COVID-19 pandemic: case studies of provision in Bolivia, Mali, Nepal, and the occupied Palestinian territory.

The COVID-19 pandemic impacted comprehensive abortion care provision. To maintain access to services while keeping individuals safe from infection, many organisations adapted their programmes. We conducted a programme evaluation to examine service adaptations implemented in Bolivia, Mali, Nepal, and the occupied Palestinian territory. Our programme evaluation used a case study approach to explore four programme adaptations through 14 group and individual interviews among 16 service providers, facility managers and representatives from supporting organisations. Data collection took place between October 2021 and January 2022. We identified adaptations to comprehensive abortion care services in relation to provision, health information systems and counselling, and referrals. Four overarching strategies emerged: (1) the use of digital technologies, (2) home and community outreach, (3) health worker optimisation, and (4) further consideration of groups in vulnerable situations. In Bolivia, the use of a messaging application increased access to confidential gender-based violence support and comprehensive abortion care. In Mali, the adoption of digital approaches created timely and complete data reporting and trained members of the community served as "interlocutors" between the communities and providers. In Nepal, an interim law expanded medical abortion provision to pharmacies, and home visits complemented facility-based services. In the occupied Palestinian territory, the use of a hotline and social media expanded access to quick and reliable information, counselling, referrals, and post-abortion care. Adaptations to comprehensive abortion care service delivery to mitigate disruptions to services during the COVID-19 pandemic may continue to benefit service quality of care, access to care, routine monitoring, as well as inclusivity and communication in the longer term.

Telehealth for Addressing Sexual and Reproductive Health and Rights Needs During the COVID-19 Pandemic and Beyond: A Hybrid Telemedicine-Community Accompaniment Model for Abortion and Contraception Services in Pakistan.

The COVID-19 pandemic led overburdened health care systems to deprioritize essential sexual and reproductive healthcare, including abortion and contraception care, while accelerating shifts in healthcare delivery to digital technologies. However, in many countries, including Pakistan, inequalities in access to digital technologies remain, presenting an opportunity for interventions that both increase access to deprioritized sexual and reproductive health and rights (SRHR) services and overcome the digital divide in delivering digital solutions to those in need of SRHR services. In June 2020, Ipas Pakistan partnered with Sehat Kahani (SK), a local health care NGO and telehealth service, and an existing network of Lady Health Workers (LHWs) to launch a novel hybrid telemedicine-community accompaniment pilot. The model linked women via LHWs with mobile devices to online providers for telemedicine consultations for SRH, including abortion services, contraception, and other gynecological consultations. In June 2020, we trained 98 LHWs and 22 telehealth doctors. Between June 2020 and March 2021, a total of 176 women were referred by LHWs for telehealth consultations. Among women who received abortion services, nearly all (90%) reported complete uterine evacuation. No serious adverse events were reported. Overall satisfaction was high; 81% reported being satisfied, and 86% said it is likely they would recommend the telehealth service to others. Data show that the provision of SRHR services via a telehealth-accompaniment model can be successfully implemented in Pakistan. Outcome data show high satisfaction and good clinical outcomes for women accessing care through this model. However, more data are needed to understand the full potential of this model. Barriers to digital health models, such as poor or inconsistent internet access, remain in places like Pakistan, especially in rural settings. This approach has its limitations but should be considered as an option in settings with similarly established community health networks and inequitable access to digital health.

Postpartum infection, pain and experiences with care among women treated for postpartum hemorrhage in three African countries: A cohort study of women managed with and without condom-catheter uterine balloon tamponade.

OBJECTIVE: We aimed to determine the risk of postpartum infection and increased pain associated with use of condom-catheter uterine balloon tamponade (UBT) among women diagnosed with postpartum hemorrhage (PPH) in three low- and middle-income countries (LMICs). We also sought women's opinions on their overall experience of PPH care. METHODS: This prospective cohort study compared women diagnosed with PPH who received and did not receive UBT (UBT group and no-UBT group, respectively) at 18 secondary level hospitals in Uganda, Egypt, and Senegal that participated in a stepped wedge, cluster-randomized trial assessing UBT introduction. Key outcomes were reported pain (on a scale 0-10) in the immediate postpartum period and receipt of antibiotics within four weeks postpartum (a proxy for postpartum infection). Outcomes related to satisfaction with care and aspects women liked most and least about PPH care were also reported. RESULTS: Among women diagnosed with PPH, 58 were in the UBT group and 2188 in the no-UBT group. Self-reported, post-discharge antibiotic use within four weeks postpartum was similar in the UBT (3/58, 5.6%) and no-UBT groups (100/2188, 4.6%, risk ratio = 1.22, 95% confidence interval [CI]: 0.45-3.35). A high postpartum pain score of 8-10 was more common among women in the UBT group (17/46, 37.0%) than in the no-UBT group (360/1805, 19.9%, relative risk ratio = 3.64, 95% CI:1.30-10.16). Most women were satisfied with their care (1935/2325, 83.2%). When asked what they liked least about care, the most common responses were that medications (580/1511, 38.4%) and medical supplies (503/1511, 33.3%) were unavailable. CONCLUSION: UBT did not increase the risk of postpartum infection among this population. Women who receive UBT may experience higher degrees of pain compared to women who do not receive UBT. Women's satisfaction with their care and stockouts of medications and other supplies deserve greater attention when introducing new technologies like UBT.

The Safety and Feasibility of a Family First Aid Approach for the Management of Postpartum Hemorrhage in Home Births: A Pre-post Intervention Study in Rural Pakistan.

OBJECTIVE: To evaluate the safety and feasibility of a Family First Aid approach whereby women and their families are provided misoprostol in advance to manage postpartum hemorrhage (PPH) in home births. METHODS: A 12-month prospective, pre-post intervention study was conducted from February 2017 to February 2018. Women in their second and third trimesters were enrolled at home visits. Participants and their families received educational materials and were counseled on how to diagnose excessive bleeding and the importance of seeking care at a facility if PPH occurs. In the intervention phase, participants were also given misoprostol and counselled on how to administer the four 200 mcg tablets for first aid in case of PPH. Participants were followed-up postpartum to collect data on use of misoprostol for Family First Aid at home deliveries (primary outcome) and record maternal and perinatal outcomes. RESULTS: Of the 4008 participants enrolled, 97% were successfully followed-up postpartum. Half of the participants in each phase delivered at home. Among home deliveries, the odds of reporting PPH almost doubled among in the intervention phase (OR 1.98; CI 1.43, 2.76). Among those reporting PPH, women in the intervention phase were significantly more likely to have received PPH treatment (OR 10.49; CI 3.37, 32.71) and 90% administered the dose correctly. No maternal deaths, invasive procedures or surgery were reported in either phase after home deliveries. CONCLUSIONS: The Family First Aid approach is a safe and feasible model of care that provides timely PPH treatment to women delivering at home in rural communities.

A cluster-randomized, non-inferiority trial comparing use of misoprostol for universal prophylaxis vs. secondary prevention of postpartum hemorrhage among community level births in Egypt.

BACKGROUND: Previous community-based research shows that secondary prevention of postpartum hemorrhage (PPH) with misoprostol only given to women with above-average measured blood loss produces similar clinical outcomes compared to routine administration of misoprostol for prevention of PPH. Given the difficulty of routinely measuring blood loss for all deliveries, more operational models of secondary prevention are needed. METHODS: This cluster-randomized, non-inferiority trial included women giving birth with nurse-midwives at home or in Primary Health Units (PHUs) in rural Egypt. Two PPH management approaches were compared: 1) 600mcg oral misoprostol given to all women after delivery (i.e. primary prevention, current standard of care); 2) 800mcg sublingual misoprostol given only to women with 350-500 ml postpartum blood loss estimated using an underpad (i.e. secondary prevention). The primary outcome was mean change in pre- and post-delivery hemoglobin. Secondary outcomes included hemoglobin ≥2 g/dL and other PPH interventions. RESULTS: Misoprostol was administered after delivery to 100% (1555/1555) and 10.7% (117/1099) of women in primary and secondary prevention clusters, respectively. The mean drop in pre- to post-delivery hemoglobin was 0.37 (SD: 0.91) and 0.45 (SD: 0.76) among women in primary and secondary prevention clusters, respectively (difference adjusted for clustering = 0.01, one-sided 95% CI: < 0.27, p = 0.535). There were no statistically significant differences in secondary outcomes, including hemoglobin drop ≥2 g/dL, PPH diagnosis, transfer to higher level, or other interventions. CONCLUSIONS: Misoprostol for secondary prevention of PPH is comparable to universal prophylaxis and can be implemented using local materials, such as underpads. TRIAL REGISTRATION: Clinicaltrials.gov NCT02226588, date of registration 27 August 2014.

How well do postpartum blood loss and common definitions of postpartum hemorrhage correlate with postpartum anemia and fall in hemoglobin?

OBJECTIVE: We aimed to better understand how well postpartum blood loss and common postpartum hemorrhage (PPH) definitions (i.e. blood loss ≥500ml = PPH, ≥1000ml = "severe" PPH) correlate with postpartum anemia and fall in hemoglobin. METHODS: Secondary analysis of data from three randomized trials that objectively measured postpartum blood loss and pre- and post-delivery hemoglobin among vaginal deliveries: one trial included 1056 home-births in Pakistan and two multi-country hospital-based trials included 1279 women diagnosed with PPH. We calculated Spearman's correlation coefficients (rs) for blood loss with hemoglobin drop and postpartum hemoglobin, and we compared PPH blood loss markers (≥500ml, ≥1000ml) with large hemoglobin drops (≥2 g/dL) and the threshold for moderate postpartum anemia (<10g/dL). RESULTS: In the Pakistan study and the multi-country trials, blood loss was weakly correlated with hemoglobin drop (Pakistan: rs = -0.220, multi-country trials: rs = -0.271) and postpartum hemoglobin (Pakistan: rs = -0.220, multi-country trials: rs = -0.316). In both the Pakistan and multi-country trials, hemoglobin drop ≥2 g/dL occurred in less than half of women with 500-999 ml blood loss (55/175 [31%] and 302/725 [42%], respectively) and was more common among women who bled ≥1000ml (19/28 [68%] and 347/554 [63%], respectively). Similarly, in the Pakistan and multi-country trials, postpartum anemia <10 g/dL was less frequent among women who bled 500-999 ml (55/175 [31%] and 390/725 [54%], respectively) and more frequent among women with ≥1000ml blood loss (20/28 [71%] and 416/554 [75%], respectively). CONCLUSIONS: Postpartum morbidity as measured by hemoglobin markers was common for women with blood loss ≥1000ml and relatively infrequent among women with blood loss 500-999ml. These findings reinforce the importance of severe PPH as the preferred outcome to be used in research. The weak correlation between blood loss and hemoglobin markers also suggests that this relationship is not straightforward and should be carefully interpreted.

Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.

BACKGROUND: Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis. METHODS: In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial. RESULTS: Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm. CONCLUSIONS: Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis. TRIAL REGISTRATION: clinicaltrials.gov # NCT01914419 , posted August 2, 2013.

Use of an at-home multilevel pregnancy test and an automated call-in system to follow-up the outcome of medical abortion.

OBJECTIVE: To assess the feasibility of using an at-home multilevel pregnancy test (MLPT) and interactive voice response (IVR) call-in system for remote follow-up of medical abortion. METHODS: A prospective pilot study was conducted among women who had a medical abortion at up to 70 days at a clinic in Mexico City, Mexico, between June 1, 2015, and January 30, 2016. Participants took an MLPT at the initial clinic visit and another MLPT at home 2 weeks later. They were requested to report their MLPT results via the IVR system and attend the clinic for follow-up evaluation. RESULTS: Of 200 women considered for inclusion, 163 (81.5%) were included in the analysis. Only 10 (6.6%) of the 152 women who had a medical abortion on or before 63 days from last menstrual period reported MLPT results to the IVR system that required clinical evaluation to assess medical abortion outcome. The remaining 142 (93.4%) women in this group reported MLPT results that ruled out ongoing pregnancy (confirmed at clinical evaluation). Reported MLPT results ruled out ongoing pregnancy among the 11 women who had a medical abortion after 63 days; however, 1 (9%) had an ongoing pregnancy at clinical evaluation. CONCLUSION: Use of MLPTs and the IVR system provided a streamlined approach to follow-up after medical 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.

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

BACKGROUND: This 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. METHODS: Four 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. RESULTS: Almost 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. CONCLUSIONS: Self-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 REGISTRATION: This study was registered on May 13, 2010, on clinicaltrials.gov as NCT01150279 .

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.

A two-pill sublingual misoprostol outpatient regimen following mifepristone for medical abortion through 70 days' LMP: a prospective comparative open-label trial.

OBJECTIVE: To test the effectiveness and acceptability of an outpatient medical abortion protocol with 200 mg mifepristone and 400 mcg sublingual misoprostol at 64-70 days' last menstrual period (LMP) and compare it to the already known efficacy of the 57-63 days' LMP gestational age range. STUDY DESIGN: We conducted a prospective, comparative open-label trial in six hospitals and clinics in Ukraine, Georgia, India and Tunisia. We enrolled 714 reproductive age women with pregnancies 57 to 70 days who presented requesting abortion. Medical abortions were managed with the current service delivery protocol (200 mg oral mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol). Data on safety, efficacy and acceptability were collected. The main outcome measure was complete abortion without surgical intervention at any point. RESULTS: A total of 703 cases were analyzable for efficacy. Success rates did not differ significantly in the two groups [57-63-day group: 94·8%; 64-70-day group: 91.9%; Relative Risk (RR): 0.79 (0.61-1.04)]. Ongoing pregnancy rates also did not differ significantly (57-63 days: 1.8%; 64-70 days: 2.2%; RR: 1.10 (0.65-1.87)]. CONCLUSION: A medical abortion regimen of 200 mg mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol is effective through 70 days' gestation and may be offered within existing outpatient abortion services. IMPLICATIONS: A regimen of 200 mg mifepristone followed in 24-48 h by 400 mcg sublingual misoprostol is effective up to 70 days' LMP. The findings have important implications for expanding access to outpatient medical abortion services in settings where the cost of misoprostol is of concern or a two-pill misoprostol regimen is the standard of care.

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.

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.

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.

OBJECTIVE: To compare the safety, efficacy, and acceptability of 400-µg sublingual misoprostol with that of manual vacuum aspiration (MVA) in 2 Egyptian hospitals. METHODS: Participating women were randomized to either MVA or misoprostol treatment for incomplete abortion. The primary outcome, complete uterine evacuation, was determined 1 week later, as were adverse effects, change in hemoglobin, acceptability, and satisfaction. RESULTS: Complete uterine evacuation was achieved in 98.3% of women who received misoprostol and 99.7% who underwent MVA (relative risk [RR] 0.99; 95% confidence interval [CI], 0.97-1.00). A decrease in hemoglobin of 2g/dL or more was comparably rare in the 2 groups (0.3% misoprostol vs 0.9% MVA; RR 0.34 [95% CI, 0.04-3.21]). Mean change in hemoglobin was also clinically similar (-0.5 g/dL misoprostol vs -0.4 g/dL MVA; P<0.01). Heavy bleeding was rare (2.4% misoprostol vs 1.6% MVA; RR 1.55 [95% CI, 0.51-4.68]) following treatment. Nearly all women (96.8% misoprostol vs 98.3% MVA) were satisfied with their treatment but those who received misoprostol were significantly more likely to prefer that method in the future (81.9% vs 62.8%; RR 1.30 [95% CI, 1.19-1.43]). CONCLUSION: The high efficacy, safety, and acceptability of 400-µg sublingual misoprostol indicate that it is analogous to surgery as a first-line treatment for incomplete abortion. Misoprostol might improve post-abortion care when resources are limited and surgical treatment is unavailable.

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.