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.

Progesterone after mifepristone: A pilot prospective single arm clinical trial for women who have changed their mind after commencing medical abortion.

AIM: This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy. METHODS: The Progesterone-After-Mifepristone-pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single-arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web-based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment. RESULTS: Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40-70 days of gestation, with progesterone being commenced within 5.7-72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events. CONCLUSION: This small study demonstrated a clinically sound protocol for researching the use of progesterone-after-mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field.

Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.

BACKGROUND: In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. METHODS: Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). RESULTS: A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). CONCLUSIONS: After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.).

Deaths and Severe Adverse Events after the use of Mifepristone as an Abortifacient from September 2000 to February 2019.

OBJECTIVES: Primary: Analyze the Adverse Events (AEs) reported to the Food and Drug Administration (FDA) after use of mifepristone as an abortifacient. Secondary: Analyze maternal intent after ongoing pregnancy and investigate hemorrhage after mifepristone alone. METHODS: Adverse Event Reports (AERs) for mifepristone used as an abortifacient, submitted to the FDA from September 2000 to February 2019, were analyzed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAEv3). RESULTS: The FDA provided 6158 pages of AERs. Duplicates, non-US, or AERs previously published (Gary, 2006) were excluded. Of the remaining, there were 3197 unique, US-only AERs of which there were 537 (16.80%) with insufficient information to determine clinical severity, leaving 2660 (83.20%) Codable US AERs. (Figure 1). Of these, 20 were Deaths, 529 were Life-threatening, 1957 were Severe, 151 were Moderate, and 3 were Mild.The deaths included: 9 (45.00%) sepsis, 4 (20.00%) drug toxicity/overdose, 1 (5.00%) ruptured ectopic pregnancy, 1 (5.00%) hemorrhage, 3 (15.00%) possible homicides, 1 (5.00%) suicide, 1 (5.00%) unknown. (Table 1).Retained products of conception and hemorrhage caused most morbidity. There were 75 ectopic pregnancies, including 26 ruptured ectopics (includes one death).There were 2243 surgeries including 2146 (95.68%) D&Cs of which only 853 (39.75%) were performed by abortion providers.Of 452 patients with ongoing pregnancies, 102 (22.57%) chose to keep their baby, 148 (32.74%) had terminations, 1 (0.22%) miscarried, and 201 (44.47%) had unknown outcomes.Hemorrhage occurred more often in those who took mifepristone and misoprostol (51.44%) than in those who took mifepristone alone (22.41%). CONCLUSIONS: Significant morbidity and mortality have occurred following the use of mifepristone as an abortifacient. A pre-abortion ultrasound should be required to rule out ectopic pregnancy and confirm gestational age. The FDA AER system is inadequate and significantly underestimates the adverse events from mifepristone.A mandatory registry of ongoing pregnancies is essential considering the number of ongoing pregnancies especially considering the known teratogenicity of misoprostol.The decision to prevent the FDA from enforcing REMS during the COVID-19 pandemic needs to be reversed and REMS must be strengthened.

"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.

Management of pain associated with up-to-9-weeks medical termination of pregnancy (MToP) using mifepristone-misoprostol regimens: expert consensus based on a systematic literature review.

Evidence-based guidelines on the management of pain associated with first-trimester medical abortion are lacking. Most published clinical trials have failed to report on this important aspect of the procedure. The aim of this comprehensive work was to provide clinical advice based on a comprehensive literature review, supplemented by the clinical experience of a group of European experts in case no evidence is available. Pain level ranged from 5 to 8 in 80% of studies where pain was measured on a 0-10 visual analogue scale; severe pain was reported by 20-80% of women. Pain assessment was rarely reported in studies. Pain treatment should be preventive and avoidance of unnecessary uterine contractions should be considered. Analgesic treatment should follow the WHO three-step ladder, starting with the use of NSAIDs and allowing for easily available back-up treatment with weak opioids.

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.

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.

Acceptability and feasibility of outpatient medical abortion with mifepristone and misoprostol up to 70 days gestation in Singapore.

OBJECTIVES: The aim of the study was to examine the acceptability and feasibility of using a combined regimen of 200 mg mifepristone and 800 µg buccal misoprostol in an outpatient abortion service in Singapore, where mifepristone is not currently registered. STUDY DESIGN: The pilot prospective study enrolled 130 women who sought termination of pregnancies up to 70 days gestation at two public hospitals in Singapore. Women received 200 mg mifepristone to take at the clinic or at home, followed 24 h later by 800 µg buccal misoprostol administered at home. A follow-up visit was scheduled seven to ten days after mifepristone to confirm the outcome of the abortion. The primary outcome was rate of successful abortion and secondary outcomes were women's preference for location of mifepristone administration and satisfaction with the method. RESULTS: The large majority of women (96.8%) had successful abortions without recourse to surgical intervention. Most women (88.2%) chose to take mifepristone at the clinic. Most women reported the side effects as acceptable (68.3%) or neutral (26.0%). Almost all women (94.4%) were very satisfied or satisfied with the method. CONCLUSIONS: Outpatient medical abortion with mifepristone and misoprostol up to 70 days gestation is acceptable and feasible and has the potential to expand available options in Singapore.

Mifepristone Pretreatment for the Medical Management of Early Pregnancy Loss.

BACKGROUND: Medical management of early pregnancy loss is an alternative to uterine aspiration, but standard medical treatment with misoprostol commonly results in treatment failure. We compared the efficacy and safety of pretreatment with mifepristone followed by treatment with misoprostol with the efficacy and safety of misoprostol use alone for the management of early pregnancy loss. METHODS: We randomly assigned 300 women who had an anembryonic gestation or in whom embryonic or fetal death was confirmed to receive pretreatment with 200 mg of mifepristone, administered orally, followed by 800 µg of misoprostol, administered vaginally (mifepristone-pretreatment group), or 800 µg of misoprostol alone, administered vaginally (misoprostol-alone group). Participants returned 1 to 4 days after misoprostol use for evaluation, including ultrasound examination, by an investigator who was unaware of the treatment-group assignments. Women in whom the gestational sac was not expelled were offered expectant management, a second dose of misoprostol, or uterine aspiration. We followed all participants for 30 days after randomization. Our primary outcome was gestational sac expulsion with one dose of misoprostol by the first follow-up visit and no additional intervention within 30 days after treatment. RESULTS: Complete expulsion after one dose of misoprostol occurred in 124 of 148 women (83.8%; 95% confidence interval [CI], 76.8 to 89.3) in the mifepristone-pretreatment group and in 100 of 149 women (67.1%; 95% CI, 59.0 to 74.6) in the misoprostol-alone group (relative risk, 1.25; 95% CI, 1.09 to 1.43). Uterine aspiration was performed less frequently in the mifepristone-pretreatment group than in the misoprostol-alone group (8.8% vs. 23.5%; relative risk, 0.37; 95% CI, 0.21 to 0.68). Bleeding that resulted in blood transfusion occurred in 2.0% of the women in the mifepristone-pretreatment group and in 0.7% of the women in the misoprostol-alone group (P=0.31); pelvic infection was diagnosed in 1.3% of the women in each group. CONCLUSIONS: Pretreatment with mifepristone followed by treatment with misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss than treatment with misoprostol alone. (Funded by the National Institute of Child Health and Human Development; PreFaiR ClinicalTrials.gov number, NCT02012491 .).

Medical abortions performed by specialists in private practice. / Medikamentell abort hos avtalespesialist.

BAKGRUNN: I Norge utføres abort kun i offentlige sykehus. I 2010 besluttet Helse- og omsorgsdepartementet å iverksette et toårig prøveprosjekt som ga avtalespesialister i fødselshjelp og kvinnesykdommer adgang til å tilby medikamentell abort før utgangen av 9. svangerskapsuke. Prøveprosjektet ble igangsatt 1.3.2015 og varte til 31.3.2017. I denne artikkelen presenterer vi de første erfaringene, herunder hvordan behandlingstilbudet ble mottatt av kvinnene. MATERIALE OG METODE: Gravide med en svangerskapsvarighet < 63 dager ultrasonografisk vurdert, som oppsøkte avtalespesialist for medikamentell abort, ble fortløpende inkludert i prosjektet (n = 476). Kvinnene inntok 200 mg mifepriston peroralt på legekontoret, 36-48 timer senere satte de selv 800 µg misoprostol vaginalt hjemme. Informasjon ble innhentet ved spørreskjema på den første konsultasjonen, under aborten og ved etterkontrollen 2-4 uker etter aborten. RESULTATER: Under aborten rapporterte 66 % (296/450) moderat eller sterk smerte og 79 % (358/451) moderat eller sterk blødning. De fleste opplevde det som trygt å være hjemme. 96 % (390/406) ville valgt medikamentell abort hos avtalespesialist ved en eventuell senere abort, og 97 % (392/405) ville anbefalt behandlingstilbudet til andre i samme situasjon. FORTOLKNING: Kvinnene i studien opplevde abortbehandling hos avtalespesialist som trygt. Tilbudet gir større valgfrihet til gravide som ønsker abort, og pasientene er tilfredse.

Self reported outcomes and adverse events after medical abortion through online telemedicine: population based study in the Republic of Ireland and Northern Ireland.

Objectives To assess self reported outcomes and adverse events after self sourced medical abortion through online telemedicine.Design Population based study.Setting Republic of Ireland and Northern Ireland, where abortion is unavailable through the formal healthcare system except in a few restricted circumstances.Population 1000 women who underwent self sourced medical abortion through Women on Web (WoW), an online telemedicine service, between 1 January 2010 and 31 December 2012.Main outcome measures Successful medical abortion: the proportion of women who reported ending their pregnancy without surgical intervention. Rates of adverse events: the proportion who reported treatment for adverse events, including receipt of antibiotics and blood transfusion, and deaths reported by family members, friends, or the authorities. Care seeking for symptoms of potential complications: the frequency with which women reported experiencing symptoms of a potentially serious complication and the proportion who reported seeking medical attention as advised.Results In 2010-12, abortion medications (mifepristone and misoprostol) were sent to 1636 women and follow-up information was obtained for 1158 (71%). Among these, 1023 women confirmed use of the medications, and follow-up information was available for 1000. At the time women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%) were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%) reported successfully ending their pregnancy without surgical intervention. Seven women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%, 1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or oral) could not be determined). No deaths resulting from the intervention were reported by family, friends, the authorities, or the media. Ninety three women (9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought attention. None of the five women who did not seek medical attention reported experiencing an adverse outcome.Conclusions Self sourced medical abortion using online telemedicine can be highly effective, and outcomes compare favourably with in clinic protocols. Reported rates of adverse events are low. Women are able to self identify the symptoms of potentially serious complications, and most report seeking medical attention when advised. Results have important implications for women worldwide living in areas where access to abortion is restricted.

Medical termination of pregnancy in general practice in Australia: a descriptive-interpretive qualitative study.

BACKGROUND: Australian Government approval in 2012 for the use of mifepristone and misoprostol for medical termination of pregnancy (MTOP) allows general practitioners (GPs) to provide early gestation abortion in primary care settings. However, uptake of the MTOP provision by GPs appears to be low and the reasons for this have been unclear. This study investigated the provision of and referral for MTOP by GPs. METHODS: We undertook descriptive-interpretive qualitative research and selected participants for diversity using a matrix. Twenty-eight semi-structured interviews and one focus group (N = 4), were conducted with 32 GPs (8 MTOP providers, 24 non MTOP providers) in New South Wales, Australia. Interviews were recorded and transcribed verbatim. A framework to examine access to abortion services was used to develop the interview questions and emergent themes identified thematically. RESULTS: Three main themes emerged: scope of practice; MTOP demand, care and referral; and workforce needs. Many GPs saw abortion as beyond the scope of their practice (i.e. a service others provide in specialist private clinics). Some GPs had religious or moral objections; others regarded MTOP provision as complicated and difficult. While some GPs expressed interest in MTOP provision they were concerned about stigma and the impact it may have on perceptions of their practice and the views of colleagues. Despite a reported variance in demand most MTOP providers were busy but felt isolated. Difficulties in referral to a local public hospital in the case of complications or the provision of surgical abortion were noted. CONCLUSIONS: Exploring the factors which affect access to MTOP in general practice settings provides insights to assist the future planning and delivery of reproductive health services. This research identifies the need for support to increase the number of MTOP GP providers and for GPs who are currently providing MTOP. Alongside these actions provision in the public sector is required. In addition, formalised referral pathways to the public sector are required to ensure timely care in the case of complications or the provision of surgical options. Leadership and coordination across the health sector is needed to facilitate integrated abortion care particularly for rural and low income women.

Efficacy and safety of mifepristone-buccal misoprostol for early medical abortion in an Australian clinical setting.

BACKGROUND: In 2014, a composite pack containing mifepristone-buccal misoprostol, indicated for use to 63 days gestation replaced the existing regimen for early medical abortion (EMA) in Australia. AIMS: To provide updated efficacy and safety information for the use of mifepristone-buccal misoprostol for EMA in Australia, and assess the effect of patient age and gestational age on efficacy. MATERIALS AND METHODS: Observational cohort study of 15 008 women attending one of 16 Marie Stopes International clinics in Australia for an EMA (gestational age ≤ 63 days) between 1 March 2013 and 30 September 2015. Administration of 200 mg oral mifepristone in-clinic was followed 24-48 h later by 800 µg buccal misoprostol self-administered at home. Method success was defined as complete abortion not requiring surgical intervention. RESULTS: Follow-up information was available for 87.14% (13 078/15 008) of women. Likelihood of follow-up was significantly lower for women from rural or remote locations (adjusted odds ratio, 0.47; P < 0.001). Medical abortion was successful in 95.16% (12 445/13 078) of women with follow-up. Higher patient and gestational ages were associated (P < 0.001) with a slight increase in method failure. There were 674 serious adverse events (5.15%), mainly due to method failure. Infection (15; 0.11%) and haemorrhage (17; 0.13%) were rare. One death was recorded (<0.01%); however, an association between EMA and cause of death, necrotising pneumonia, was not established. CONCLUSION: Mifepristone-buccal misoprostol is an effective and safe alternative to surgical termination of pregnancy up to 63 days gestation.

Simultaneous Administration Compared With a 24-Hour Mifepristone-Misoprostol Interval in Second-Trimester Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare outcomes with simultaneous administration of mifepristone and misoprostol with a regimen in which the drugs are administered at a 24-hour interval for second-trimester abortion. METHODS: In this placebo-controlled, double-blind trial, participants were randomized to receive mifepristone either 24 hours before or at the same time as misoprostol. Participants were hospitalized to receive 400 micrograms buccal misoprostol at 3-hour intervals up to 48 hours or until uterine expulsion. The primary outcome was the proportion of women who experienced uterine expulsion within 24 hours after the first misoprostol dose and this required 504 women to examine our hypothesis that this rate would be 85% in the 24-hour interval arm compared with 70% in the simultaneous arm. Secondary outcomes included total abortion time from mifepristone and misoprostol. RESULTS: From February 2013 to April 2014, 509 women were enrolled. Women in the 24-hour interval arm were more likely to abort within 24 hours (94.4% compared with 85.0%, relative risk 1.11, 95% confidence interval [CI] 1.05-1.18). At 48 hours, the rate was similar in the two arms (96.8% [24-hour interval] and 95.7% [simultaneous], relative risk 1.01, 95% CI 0.97-1.04). Median misoprostol dosing time was shorter in the 24-hour interval arm (7.7 compared with 13 hours; P<.001) and consistent with the median misoprostol doses required (three compared with five; P<.001). Median time from mifepristone to uterine expulsion was longer in the 24-hour interval arm (32.3 compared with 13 hours; P<.001). Both regimens had high acceptability rates and reported similar side effects and pain scores. CONCLUSION: Administering mifepristone and misoprostol simultaneously results in lower expulsion rates within 24 hours of taking misoprostol, longer median misoprostol treatment times, and requires more misoprostol doses. At 48 hours, both regimens work equally well. Simultaneous dosing results in less total time from the first clinical contact to complete abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01768299.

Two prophylactic medication approaches in addition to a pain control regimen for early medical abortion < 63 days' gestation with mifepristone and misoprostol: study protocol for a randomized, controlled trial.

BACKGROUND: Pain is often cited as one of the worst features of medical abortion. Further, inadequate pain management may motivate some women to seek unnecessary clinical care. There is a need to identify effective methods for pain control in this setting. METHODS/DESIGN: We propose a randomized, placebo-controlled trial. 576 participants (288 nulliparous; 288 parous) from study sites in Nepal, South Africa and Vietnam will be randomly allocated to one of three treatments: (1) ibuprofen 400 mg PO and metoclopramide 10 mg PO; (2) tramadol 50 mg PO and a placebo; or (3) two placebo pills, to be taken immediately before misoprostol and repeated once four hours later. All women will be provided with supplementary analgesia for use as needed during the medical abortion. We hypothesize that women receiving prophylactic analgesia will report lower maximal pain scores in the first 8 h following misoprostol administration compared to women receiving placebos for medical abortion through 63 days' gestation. Our primary objective is to determine whether prophylactic administration of ibuprofen and metoclopramide or tramadol provides superior pain relief compared to analgesia administration after pain begins, measured during the first eight hours after misoprostol administration. Secondary objectives include identifying covariates associated with higher reported pain scores; determining any impact of the study medicines on medical abortion success; and, qualitatively exploring women's physical experiences of medical abortion, especially related to pain, and how can they be improved. Data sources include medical records, participant symptom diaries and interview data obtained on the day of enrollment, during the medical abortion, and at follow-up. Participants will be contacted via telephone on day 3 and return for follow-up will occur approximately 14 days after mifepristone, concluding study participation. A subset of 42 women will also be invited to undergo in-depth qualitative interviews following study completion. DISCUSSION: Although pain is one of the most common side effects encountered with medical abortion, little is known about optimal pain management for this process. This multi-arm trial design offers an efficient approach to evaluating two prophylactic pain management regimens compared to use of pain medication as needed. TRIAL REGISTRATION: ACTRN12613000017729 (Prospectively registered 8/1/2013).

Refocusing the Undue Burden Test: Inconsistent Interpretations Pose a Substantial Obstacle to Constitutional Legislation.

Decades after Roe, debate over abortion remains as contentious as ever. States continue to pass regulations burdening the abortion right, but lack clear guidance on how to evaluate such regulations using the undue burden test. This Article chronicles Supreme Court jurisprudence on abortion and examines how the current circuit split surrounding FDA-protocol legislation fits within the larger framework. Finally, this Article applies the proper version of the undue burden test to FDA-protocol legislation, which resolves the circuit split and provides lower courts with a clear means of analyzing abortion issues moving forward.