Retrospective cohort study comparing success of medical management of early pregnancy loss in pregnancies conceived with and without medical assistance.

OBJECTIVE: To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who conceived without medical assistance and those who conceived through in vitro fertilization (IVF), after fresh or frozen embryo transfer, and evaluate for the predictive factors of success, time to first passage of tissue, and time to complete resolution of pregnancy. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Women who presented with EPL below 13 weeks of gestation between June 2013 and July 2021 who were managed medically with mifepristone 200 mg orally and misoprostol 800 mcg vaginally were included in the study. INTERVENTION(S): Medical management with mifepristone and misoprostol; conception without medical assistance vs. post-IVF, after fresh or frozen embryo transfer. MAIN OUTCOME MEASURE(S): We evaluated overall success and performed subgroup analysis according to the mode of conception and compared fresh vs. frozen-thawed embryo transfers for IVF pregnancies. In all groups, we also calculated success according to gestational age and compared the time to first passage of tissue. The potential predictive factors of treatment success were analyzed. The side effects and complications of treatment were recorded. RESULT(S): A total of 930 women were included in the study, 99 (11%) of whom achieved pregnancy after IVF. The overall success of medical treatment was 89% with no statistically significant difference according to the mode of conception (89% vs. 89%) or type of transfer (fresh 89% vs. frozen 89%). Only lower gestational age by sonography was independently predictive of treatment success, showing a negative regression coefficient of ß = -0.333 and an odds ratio of 0.717. The mean time to first passage of tissue was 5.0 ± 2.1 hours. Altogether, 666 women (72%) showed pregnancy resolution on the day of medication administration, an additional 110 women at 1-week follow-up, and a further 74 women after ≥4 weeks on ultrasound. CONCLUSION(S): Medical management of EPL with mifepristone and misoprostol is a highly successful treatment option that results in completed abortion in a timely fashion in both pregnancies conceived without medical assistance and those conceived after IVF.

Pharmacist dispensing of the abortion pill in Canada: Diffusion of Innovation meets integrated knowledge translation.

BACKGROUND: Since Canadian drug regulatory approval of mifepristone for medical abortion in 2015 and its market availability in January 2017, the role of pharmacists in abortion provision has changed rapidly. We sought to identify the factors that influenced the initiation and provision of medical abortion from the perspectives of Canadian pharmacists, bridging two frameworks - Diffusion of Innovation in Health Service Organizations and integrated knowledge translation. METHODS: We conducted one-on-one semi-structured interviews with pharmacists residing in Canada who intended to stock and dispense mifepristone within the first year of availability. Our data collection, analysis, and interpretation were guided by reflexive thematic analysis and supported by an integrated knowledge translation partnership with pharmacy stakeholders. RESULTS: We completed interviews with 24 participants from across Canada: 33% had stocked and 21% had dispensed mifepristone. We found that pharmacists were willing and able to integrate medical abortion care into their practice and that those who had initiated practice were satisfied with their dispensing experience. Our analysis indicated that several key Diffusion of Innovation constructs impacted the uptake of mifepristone, including: innovation (relative advantage, complexity and compatibility, technical support), system readiness (innovation-system fit, dedicated time, resources), diffusion and dissemination (expert opinion, boundary spanners, champions, social networks, peer opinions), implementation (external collaboration), and linkage. Participants' experiences suggest that integrated knowledge translation facilitated evidence-based changes to mifepristone dispensing restrictions, and communication of those changes to front line pharmacists. CONCLUSIONS: We illustrate how Diffusion of Innovation and integrated knowledge translation may work together as complimentary frameworks for implementation science research. Unlike in the USA, UK, and other highly regulated settings globally, pharmacists in Canada are permitted to dispense mifepristone for medical abortion. We contribute to literature that shows that mifepristone dispensed outside of hospitals, clinics, and medical offices is safe and acceptable to both patients and prescribers. This finding is of particular importance to the current COVID-19 pandemic response and calls for continued and equitable access to abortion care in primary practice.

Factors Associated With Use of an Online Telemedicine Service to Access Self-managed Medical Abortion in the US.

Importance: People in the US have been seeking self-managed abortions outside the formal health care system using medications obtained through online telemedicine. However, little is known about this practice, including potential motivating factors. Objective: To examine individual reasons for accessing medication abortion through an online telemedicine service as well as associations between state- and county-level factors and the rate of requests. Design, Setting, and Participants: This population-based cross-sectional study examined all requests for self-managed medication abortion through an online consultation form available from Aid Access, a telemedicine service in the US, between March 20, 2018, and March 20, 2020. Main Outcomes and Measures: Individual-level reasons for accessing the telemedicine service were examined as well as the rate of requests per 100 000 women of reproductive age by state. Zip code data provided by individuals making requests were used to examine county-level factors hypothesized to be associated with increased demand for self-managed abortion: distance to a clinic (calculated using location data for US abortion clinics) and the population proportion identifying as a member of a racial/ethnic minority group, living below the federal poverty level, and having broadband internet access (calculated using census data). Results: During the 2-year study period, 57 506 individuals in 2458 counties in 50 states requested self-managed medication abortion; 52.1% were aged 20 to 29 years (mean [SD] age, 25.9 [6.7] years), 50.0% had children, and 99.9% were 10 weeks' pregnant or less. The most common reasons cited by individuals making requests were the inability to afford in-clinic care (73.5%), privacy (49.3%), and clinic distance (40.4%). States with the highest rate of requests were Louisiana (202.7 per 100 000 women) and Mississippi (199.9 per 100 000 women). At the county level, an increase of 1 SD (47 miles) in distance to the nearest clinic was significantly associated with a 41% increase in requests (incidence rate ratio, 1.41; 95% CI, 1.31-1.51; P < .001), and a 10% increase in the population living below the federal poverty level was significantly associated with a 20% increase in requests (incidence rate ratio, 1.20; 95% CI, 1.13-1.28; P < .001). Conclusions and Relevance: In this cross-sectional study, clinic access barriers were the most commonly cited reason for requesting self-managed medication abortion using an online telemedicine service. At the county level, distance to an abortion clinic and living below the federal poverty level were associated with a higher rate of requests. State and federal legislation could address these access barriers.

Abortion exceptionalism and the mifepristone REMS.

Since its initial approval, mifepristone has been regulated with a strictness out of proportion to its risks. This paper explores how the regulation of mifepristone, specifically the Risk Evaluation and Mitigation Strategies (REMS) requirements, are a manifestation of abortion exceptionalism-the phenomenon of abortion being treated differently under the law than other comparable health care. The weight of medical and public health evidence demonstrates that mifepristone is extremely safe and the REMS are unnecessary. In fact, the mifepristone REMS is neither justified by the absolute risk of the medication itself, nor comprehensible as a logical response to the risks actually posed by mifepristone. Nevertheless, the REMS remain in place. From July 2020 through January 2021, enforcement of the REMS elements requiring in-person distribution of mifepristone were enjoined by court order due the COVID-19 pandemic. In other words, COVID-19 created a context so exceptional as to temporarily outweigh abortion exceptionalism. However, the reprieve did not last-in January 2021, the Supreme Court ruled to dissolve the injunction, allowing FDA to resume enforcement of the in-person requirements. In response, advocates called on the incoming Biden administration to direct FDA to suspend enforcement once more. This regulatory whiplash is itself further evidence that the REMS flow from political, rather than scientific, concerns. Abortion exceptionalism is apparent in the specific requirements of the REMS, and it is also apparent in the precarity of the regulatory scheme itself.

Comparison of surgical versus medical termination of pregnancy between 13-20 weeks of gestation in Ethiopia: A quasi-experimental study.

BACKGROUND: Dilation and evacuation is a method of second trimester pregnancy termination introduced recently in Ethiopia. However, little is known about the safety and effectiveness of this method in an Ethiopian setting. Therefore, the study is intended to determine the safety and effectiveness of dilation and evacuation for surgical abortion as compared to medical abortion between 13-20 weeks' gestational age. METHODS: This is a quasi-experimental study of women receiving second trimester termination of pregnancy between 13-20 weeks. Patients were allocated to either medical or surgical abortion based on their preference. A structured questionnaire was used to collect demographic information and clinical data upon admission. Procedure related information was collected after the procedure was completed and before the patient was discharged. Additionally, women were contacted 2 weeks after the procedure to evaluate for post-procedural complications. The primary outcome of the study was a composite complication rate. Data were collected using Open Data Kit and then analyzed using Stata version 14.2. Univariate analyses were performed using means (standard deviation), or medians (interquartile range) when the distribution was not normal. Multiple logistic regression was also performed to control for confounders. RESULTS: Two hundred nineteen women chose medical abortion and 60 chose surgical abortion. The composite complication rate is not significantly different among medical and surgical abortion patients (15% versus 10%; p = 0.52). Nine patients (4.1%) in the medical arm required additional intervention to complete the abortion, while none of the surgical abortion patients required additional intervention. Median (IQR) hospital stay was significantly longer in the medical group at 24 (12-24) hours versus 6(4-6) hours in the surgical group p<0.001. CONCLUSION: From the current study findings, we concluded that there is no difference in safety between surgical and medical methods of abortion. This study demonstrates that surgical abortion can be used as a safe and effective alternative to medical abortion and should be offered equivalently with medical abortion, per the patient's preference.

Second trimester medical abortion in a primigravida with lupus nephritis and rapidly progressive renal failure: challenges and outcome.

In the second trimester, medical abortion is preferred as it is less invasive, and the surgical method carries more risk. There is a paucity of published literature on medical abortion in women with renal failure requiring haemodialysis. We came across a woman who presented with rapidly progressive renal failure at 18 weeks of gestation and required therapeutic abortion. We are reporting the challenges, outcomes, and precautions to be taken while performing a medical abortion in such a case.

Medication Abortion Up to 70 Days of Gestation.

Medication abortion, also referred to as medical abortion, is a safe and effective method of providing abortion. Medication abortion involves the use of medicines rather than uterine aspiration to induce an abortion. The U.S. Food and Drug Administration (FDA)-approved medication abortion regimen includes mifepristone and misoprostol. The purpose of this document is to provide updated evidence-based guidance on the provision of medication abortion up to 70 days (or 10 weeks) of gestation. Information about medication abortion after 70 days of gestation is provided in other ACOG publications [1].

Simultaneous compared to interval administration of mifepristone and misoprostol for medical abortion up to 10+0 weeks' gestation: a systematic review with meta-analyses.

BACKGROUND: Medical abortion with mifepristone and misoprostol usually involves an interval of 36-48 hours between administering these drugs; however, it is possible that the clinical efficacy at early gestations may be maintained when the drugs are taken simultaneously. The objective of this systematic review was to determine the safety and effectiveness of simultaneous compared with interval administration of mifepristone and misoprostol for abortion up to 10+0 weeks' gestation. METHODS: We searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily, and Epub Ahead-of-Print, In-Process & Other Non-Indexed Citations; and Cochrane Library on 11 December 2019. We included randomised controlled trials (RCTs), published in English from 1985, comparing simultaneous to interval administration of mifepristone and misoprostol for early abortion. Risk of bias was assessed using the Cochrane Collaboration checklist for RCTs. Meta-analysis of risk ratios (RRs) using the Mantel-Haenszel method were performed. The quality of the evidence was assessed using GRADE. RESULTS: Meta-analyses of three RCTs (n=1280) showed no differences in 'ongoing pregnancy' (RR 1.78, 95% CI 0.38 to 8.36), 'haemorrhage requiring transfusion or ≥500 mL blood loss' (RR 0.11, 95% CI 0.01 to 2.03) and 'incomplete abortion with the need for surgical intervention' (RR 1.30, 95% CI 0.76 to 2.25) between the interventions. Individual study results showed no difference in patient satisfaction, or 'need for repeat misoprostol', although 'time to onset of bleeding or cramping' was longer after simultaneous than interval administration. The quality of evidence was very low to moderate. CONCLUSION: The published data support the use of simultaneous mifepristone and misoprostol for medical abortion up to 9+0 weeks in women who prefer this method of administration.

"We've got rights and yet we don't have access": Exploring patient experiences accessing medication abortion in Australia.

OBJECTIVES: Across Australia, multiple strategies have emerged to decentralize abortion care and increase access to mifepristone, including incorporating medication abortion into primary care and offering the mifepristone and misoprostol regimen via telemedicine. We aimed to explore the experiences of patients accessing medication abortion care across these different health service delivery formats and different geographic areas. STUDY DESIGN: We conducted in-depth interviews with 22 people from across Australia who had used mifepristone for abortion. We audio-recorded and transcribed all interviews and managed our data with ATLAS.ti. We used deductive and inductive techniques to analyze these data for content and themes. RESULTS: Although participants were generally satisfied with the abortion care they received, many described medication abortion care in Australia as inaccessible and confusing to find. Our participants incurred variable and often significant financial costs when obtaining their abortion and many reported that their interactions with general practitioners when trying to locate an abortion provider were uninformative and stigmatizing. Participants were enthusiastic about obtaining medication abortion through a variety of service delivery modalities, including telemedicine, and believed these strategies could increase equitable and affordable access. CONCLUSIONS: Barriers to finding and accessing abortion care persist across Australia. Efforts to challenge the over-regulation of mifepristone, increase the affordability of medication abortion, and enhance training opportunities to educate a variety of clinicians about medication abortion and support provision from a range of providers appear warranted. IMPLICATIONS: The continued over regulation of mifepristone creates barriers for incorporating medication abortion into primary care settings and has significant implications for patient access and abortion stigma. Regulatory reform and provider education and training have the potential to improve abortion patients' experiences with medication abortion.

Intubation and intensive care after laminaria anaphylaxis in second-trimester abortion.

Laminaria are cervical dilators inserted for several days preceding second-trimester abortions and other uterine procedures. Our patient was intubated after a life-threatening anaphylactic reaction to laminaria prior to her surgical abortion. Abortions with laminaria dilators are frequently performed outpatient across the United States. Due to stigma, increasing restrictions, and forced closure of family planning clinics, these procedures are often obtained covertly and remotely. Patients may present obtunded, in shock, without records or proxy, and with no external evidence of the allergen's location or continued presence. Emergency and critical care physicians may consider this etiology in obtunded women with anaphylaxis who are responding poorly to standard care.

Reconceptualizing safe abortion and abortion services in the age of abortion pills: A discussion paper.

At the conference "Developing an Advocacy Agenda for Abortion in the 21st Century and Making Change Happen" held on 5-7 September 2018, Lisbon, Portugal, organized by the International Campaign for Women's Right to Safe Abortion, it was argued that abortion services not only need to be treated as a bona fide form of health care but also completely reconceptualized, particularly because of the influence of medical abortion pills. It emerged, however, that there is no consensus on how this reconceptualization should be configured. Indeed, substantial differences arose, or so it appeared, complicated not only by different exigencies in national settings but also reflecting differing perspectives, specifically, those held primarily by health professionals compared to those held by advocates who felt they spoke for women needing abortions. In the course of these discussions, questions emerged on how much women should be able to do on their own, whether and why services were necessary in every case, where services should be located, what they should offer, who should provide them, and who should be in charge of the process. The biggest discussion was over the extent to which women can safely self-manage use of medical abortion pills for abortion in both the first and second trimester, and to what extent health professional control should be relinquished. Regardless of these arguments, however, since 1988 with the discovery in Brazil that misoprostol is an abortifacient, over-the-counter access to medical abortion (MA) pills began to put self-management of abortion on the map. Today, self-management is happening in almost every country, and we have no idea how many abortions are taking place anymore. Moreover, because of the work of safe abortion information hotlines, there is a growing body of evidence that self-management of abortion by women is safe - or at least far less unsafe than what prevailed in the past. Looking beyond the abortion rights movement, the crux of the issue is whether the state should continue to control abortion, with power over individual decisions delegated to the medical profession - or whether, as has been happening at a snail's pace for the last half century, and as with contraception and emergency contraception too - control can and should be more and more in women's hands. This paper examines these perspectives and attempts to describe what a consensus might look like. It concludes that convincing governments and conservative health professionals to accept a large dose of self-management will not be easy.

Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.

OBJECTIVE: To estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone. METHODS: We planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44-63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14-16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment. RESULTS: We enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported. CONCLUSION: We could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03774745.

Effect of the addition of osmotic dilators to medical induction of labor abortion: A before-and-after study.

OBJECTIVES: The main objective of this study was to assess the induction-to-delivery interval with or without the use of osmotic dilators for induced abortion. As secondary objectives, women outcomes were assessed. STUDY DESIGN: This retrospective single-center observational before and after study reviewed records from a university hospital maternity unit from 2002 through 2016 and included all women undergoing abortion for medical reasons at and after 14 weeks of gestation. Two groups were compared: group "no dilators", which used first misoprostol without dilators, and group "dilators", which used osmotic dilators before misoprostol administration. The main outcome was the induction-to-delivery interval. RESULTS: The study included 491 women: 383 in group "no dilators" and 108 in group "dilators". The induction-delivery interval was significantly lower in the group "dilators" compared to "no dilators" (427.7 min vs 639.7 min, P < 0.001), as was the cumulative misoprostol dose (990 µg vs 1449 µg, P < 0.001). The delivery rate within 6 h was significantly higher in the "dilators" group compared to "no dilators" group (50.0% vs 29.8%, P = 0.002). CONCLUSION: The use of osmotic dilators for cervical ripening before administration of misoprostol for induced abortion appears to be effective in reducing the induction-delivery interval.

Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: study protocol for a randomized double blinded placebo-controlled comparison (Triple M Trial).

BACKGROUND: Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to remove the products of conception from the uterus. Curettage, although highly effective, is associated with a risk of complications; medical treatment with misoprostol is a safe and less expensive alternative. Unfortunately, after 1 week of expectant management in case of EPF, medical treatment with misoprostol has a complete evacuation rate of approximately 50%. Misoprostol treatment results may be improved by pre-treatment with mifepristone; its effectiveness has already been proven for other indications of pregnancy termination. This study will test the hypothesis that, in EPF, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes). METHODS: The trial will be performed multi-centred, prospectively, two-armed, randomised, double-blinded and placebo-controlled. Women with confirmed EPF by ultrasonography (6-14 weeks), managed expectantly for at least 1 week, can be included and randomised to pre-treatment with oral mifepristone (600 mg) or oral placebo (identical in appearance). Randomisation will take place after receiving written consent to participate. In both arms pre-treatment will be followed by oral misoprostol, which will start 36-48 h later consisting of two doses 400 µg (4 hrs apart), repeated after 24 h if no tissue is lost. Four hundred sixty-four women will be randomised in a 1:1 ratio, stratified by centre. Ultrasonography 2 weeks after treatment will determine short term treatment effect. When the gestational sac is expulsed, expectant management is advised until 6 weeks after treatment when the definitive primary endpoint, complete or incomplete evacuation, will be determined. A sonographic endometrial thickness < 15 mm using only the allocated therapy by randomisation is considered as successful treatment. Secondary outcome measures (patient satisfaction, complications, side effects and costs) will be registered using a case report form, patient diary and validated questionnaires (Short Form 36, EuroQol-VAS, Client Satisfaction Questionnaire, iMTA Productivity Cost Questionnaire). DISCUSSION: This trial will answer the question if, in case of EPF, after at least 1 week of expectant management, sequential treatment with mifepristone and misoprostol is more effective than misoprostol alone to achieve complete evacuation of the products of conception. TRIAL REGISTRATION: Clinicaltrials.gov (d.d. 02-07-2017): NCT03212352. Trialregister.nl (d.d. 03-07-2017): NTR6550. EudraCT number (d.d. 07-08-2017): 2017-002694-19. File number Commisie Mensgebonden Onderzoek (d.d. 07-08-2017): NL 62449.091.17.

Feasibility of a hospital outpatient day procedure for medication abortion at 13-18 weeks gestation: Findings from Nepal.

OBJECTIVES: To evaluate the safety, acceptability and feasibility of a one-day outpatient medication abortion service at gestations 13-18 weeks. STUDY DESIGN: Open-label prospective study in which participants received mifepristone 200 mg orally to swallow at home or at the clinic followed 24 h later by misoprostol 400 mcg buccally. They presented to the outpatient clinic 24-48 h after mifepristone for misoprostol 400 mcg buccally every three hours (no maximum dose). The primary outcome was successful abortion without transfer to overnight inpatient care. Secondary outcomes included time to abortion from initial misoprostol dose, safety, additional interventions and side effects. RESULTS: We enrolled 230 women from December 2017 to November 2018. Approximately nine of ten (n = 206, 89.6%) achieved a successful abortion without transfer to overnight care. Twenty-four were transferred to overnight inpatient care; of these 18 were to manage a complication, five for incomplete abortion and two by choice. Among these 24, three women experienced an SAE. The median time to successful abortion from time of the first misoprostol dose was 7.2 h (range: 0.75-92.3), with an average of three misoprostol doses. Most participants expelled the fetus and the placenta at or around the same time; median time between fetal and placental expulsion was 15 minutes (range: 0-4.5 h). Fifteen participants (6.6%) received more than five misoprostol doses and were transferred to inpatient care. Administration of more than five doses of misoprostol was associated with nulliparity. Provision of antibiotics (27.9%, n = 64), manual removal of placenta (15.3%, n = 35), uterotonics (4.4%, n = 10) and surgical interventions (4.4%, n = 10) were also reported. About one in four participants experienced nausea, vomiting and chills; fever was infrequent (2.5%, n = 5). CONCLUSIONS: For gestations 13-18 weeks, an outpatient day process for medication abortion is safe, effective and feasible. IMPLICATIONS: Medication abortion in 13 - 18 weeks need not be limited to inpatient care; nine of ten cases can be managed as an outpatient day service.

A systematic review of the effectiveness, safety, and acceptability of medical management of intrauterine fetal death at 14-28 weeks of gestation.

BACKGROUND: Optimal dose, interval, and administration route of misoprostol with added benefit of mifepristone for management of second trimester intrauterine fetal death (IUFD) are not established. OBJECTIVES: To assess effectiveness, safety, and acceptability of medical management of second trimester IUFD. SEARCH STRATEGY: Research databases from January 2006 to October 2018. SELECTION CRITERIA: Randomized controlled trials with IUFD cases at 14-28 weeks of gestation. DATA COLLECTION AND ANALYSIS: We screened and extracted data, assessed risk of bias, conducted analyses, and assessed overall certainty of the evidence. MAIN RESULTS: Sixteen trials from 1695 citations. When misoprostol is used alone, 400 µg is more effective than 200 µg (RR 0.78; 95% CI, 0.66-0.92, moderate certainty evidence); the sublingual route is more effective than the oral route (RR 0.88; 95% CI, 0.70-1.11, low certainty evidence). There may be little to no difference between the sublingual and vaginal route (RR 0.93; 95% CI, 0.85-1.03, low certainty evidence). Certainty of evidence related to mifepristone-misoprostol regimens and safety and acceptability is very low. CONCLUSIONS: Misoprostol 400 µg every 4 hours, sublingually or vaginally, may be effective. We cannot draw conclusions about safety and acceptability, or about the added benefits of mifepristone.