Early pregnancy loss medical management in clinical practice.

OBJECTIVES: This study aimed to review clinical practice outcomes of early pregnancy loss (EPL) medical management using mifepristone and misoprostol outside of a clinical trial setting. STUDY DESIGN: In this retrospective cohort study, we reviewed a deidentified database of patients who received mifepristone-misoprostol for EPL from May 2018 to May 2021 at our academic center-based clinic, which was a study site for a multicenter mifepristone-misoprostol EPL trial completed in March 2018. All patients received mifepristone 200 mg orally and misoprostol 800 mcg vaginally or buccally, with clinic follow-up typically scheduled within 1 week. The primary outcome was successful medical management, defined as management without the need for aspiration, and the secondary outcomes included additional interventions and indications, follow-up ultrasonography findings, and adverse events requiring treatment. RESULTS: We treated 90 patients with a median ultrasound-measured gestational size of 49 (range 30-80) days and median time from mifepristone to misoprostol of 24 (range 8-66) hours. Follow-up was completed in clinic by 80 (88.9%), completed remotely by five (5.6%), and not completed by five (5.6%) patients. Overall, 76 (95% CI 82.9%-96.0%) of 85 patients (89.4%) with follow-up were successfully managed without uterine aspiration. Eighty patients had initial follow-up ultrasonography interpreted as gestational sac expulsion; seven (8.8%) of these ultimately underwent aspiration, including one patient who had a previously undiagnosed cesarean scar ectopic pregnancy. Two patients had significant safety outcomes: one pelvic infection and one blood transfusion during aspiration in the patient with a cesarean scar ectopic pregnancy. CONCLUSIONS: Outside of a clinical trial setting, medical management of EPL with mifepristone and misoprostol remains effective and safe. IMPLICATIONS: Medical management of EPL with mifepristone and misoprostol is effective and safe outside of a clinical trial setting. A standardized protocol based on the best available clinical trial evidence can be used in clinical practice for the medical management of EPL.

Development of a Spanish-language drug facts label prototype for a combination mifepristone and misoprostol medication abortion product.

OBJECTIVE: To develop a Spanish-language drug facts label prototype for medication abortion. STUDY DESIGN: We translated a drug facts label prototype for medication abortion and conducted cognitive video interviews with reproductive age native Spanish speakers to assess and improve its readability. RESULTS: Thirty-eight people ages 15 to 48 completed cognitive interviews, found the drug facts label easy to understand and suggested minor improvements. CONCLUSION: Conducting cognitive interviews with native Spanish speakers is a helpful tool to improve readability of a translated label. IMPLICATIONS: This drug facts label can help to ensure that Spanish speakers have access to easy-to-understand instructions of how to take medication abortion without clinical supervision.

Clinical analysis of second-trimester pregnancy termination after previous caesarean delivery in 51 patients with placenta previa and placenta accreta spectrum: a retrospective study.

BACKGROUNDS: Pregnancy termination during the second trimester in patients with placenta previa and placenta accreta spectrum (PAS) is a complex and challenging clinical problem. Based on our literature review, there has been a relative increase in the number of such cases being treated by hysterotomy and/or local uterine lesion resection and repair. In the present study, a retrospective analysis was conducted to compare the clinical outcomes when different management strategies were used to terminate pregnancy in the patients with placenta previa and PAS. METHODS: A total of 51 patients who underwent pregnancy termination in the second trimester in Beijing Obstetrics and Gynecology Hospital between June 2013 and December 2018 were retrospectively analyzed in this study. All patients having previous caesarean delivery (CD) were diagnosed with placenta previa status and PAS. RESULTS: ① Among the 51 patients, 16 cases received mifepristone and misoprostol medical termination, 15 cases received mifepristone and Rivanol medical termination, but 1 of them was transferred to hysterotomy due to failed labor induction, another 20 cases were performed planned hysterotomy. There was no placenta percreta cases and uterine artery embolization (UAE) was all performed before surgery.② There were 31 cases who underwent medical termination and 30 cases were vaginal delivery. Dilation and evacuation (D&E) were used in 20 cases of medical abortion failure and in all 30 cases of difficult manual removal of placental tissue. ③ A statistically significant difference was found among the three different strategies in terms of gestational weeks, the type of placenta previa status, main operative success rate and ß-HCG regression time (P < 0.05). ④ There were 4(7.8%) cases who were taken up for hysterectomy because of life-threatening bleeding or severe bacteremia during or after delivery and hysterotomy. The uterus was preserved with the implanted placenta partly or completely left in situ in 47(92.2%) cases. Combined medical and/or surgical management were used for the residual placenta and the time of menstrual recovery was 52(range: 33 to 86) days after pregnancy termination. CONCLUSIONS: Terminating a pregnancy by vaginal delivery through medical induction of labor may be feasible if clinicians have an overall understanding of gestational age, the type of placenta previa status, the type of placenta accreta, and patients concerns about preserving fertility. A collaborative team effort in tertiary medical centers with a very experience MDT and combined application of multiple methods is required to optimize patient outcomes.

Pain Associated With Cervical Priming for First-Trimester Surgical Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of cervical priming with mifepristone with that of misoprostol on pain perception during surgical induced abortion under paracervical block. METHODS: We conducted a randomized, single-blind, two-center study of women undergoing surgical induced abortion at less than 14 weeks of gestation under paracervical block. Participants were randomized to receive cervical priming with 200 mg of oral mifepristone 36 hours or 400 micrograms buccal misoprostol 3 hours before surgery. The primary outcome was pain during mechanical cervical dilation evaluated by a 100-mm visual analog scale (VAS). Secondary outcomes were pain during aspiration, preoperative and postoperative pain, participant satisfaction, duration of the procedure, occurrence of complications, and ease of performing the procedure (assessed by a 100-mm VAS). We estimated that 110 women would have to be included to have 90% power to detect a 13mm-difference of VAS for pain. RESULTS: Between June 2017 and May 2019, 314 women were eligible and 110 were randomized (55 in each group). Patient characteristics were similar in the two groups. The mean VAS score during mechanical cervical dilation was lower in the mifepristone group (35.6±21 vs 43.5±21, P=.04) as was the mean VAS during aspiration (34±24 vs 47.8±23, P=.003). The preoperative and postoperative mean VAS, satisfaction and duration of procedures were similar between groups. The procedure was significantly easier to perform in the mifepristone group (88±16 vs 80±23, P=.004). CONCLUSION: Cervical priming with mifepristone for surgical induced abortion under paracervical block up to 14 weeks of gestation is more effective than misoprostol in reducing pain perception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03043014.

The future of abortion is now: Mifepristone by mail and in-clinic abortion access in the United States.

The COVID-19 pandemic disrupted health care delivery in all aspects of medicine, including abortion care. For 6 months, the mifepristone Risk Evaluation and Mitigation Strategy (REMS) was temporarily blocked, allowing for the remote provision of medication abortion. Remote medication abortion may become a dominant model of care in the future, either through the formal health system or through self-sourced, self-managed abortion. Clinics already face pressure from falling abortion rates and excessive regulation and with a transition to remote abortion, may not be able to sustain services. Although remote medication abortion improves access for many, those who need or want in-clinic care such as people later in pregnancy, people for whom abortion at home is not safe or feasible, or people who are not eligible for medication abortion, will need comprehensive support to access safe and appropriate care. To understand how we may adapt to remote abortion without leaving people behind, we can look outside of the U.S. to become familiar with emerging and alternative models of abortion care.

Expansion of a direct-to-patient telemedicine abortion service in the United States and experience during the COVID-19 pandemic.

OBJECTIVE: To present updated evidence on the safety, efficacy and acceptability of a direct-to-patient telemedicine abortion service and describe how the service functioned during the COVID-19 pandemic. STUDY DESIGN: We offered the study at 10 sites that provided the service in 13 states and Washington DC. Interested individuals obtained any needed preabortion tests locally and had a videoconference with a study clinician. Sites sent study packages containing mifepristone and misoprostol by mail and had remote follow-up consultations within one month by telephone (or by online survey, if the participant could not be reached) to evaluate abortion completeness. The analysis was descriptive. RESULTS: We mailed 1390 packages between May 2016 and September 2020. Of the 83% (1157/1390) of abortions for which we obtained outcome information, 95% (1103/1157) were completed without a procedure. Participants made 70 unplanned visits to emergency rooms or urgent care centers for reasons related to the abortion (6%), and 10 serious adverse events occurred, including 5 transfusions (0.4%). Enrollment increased substantially with the onset of COVID-19. Although a screening ultrasound was required, sites determined in 52% (346/669) of abortions that occurred during COVID that those participants should not get the test to protect their health. Use of urine pregnancy test to confirm abortion completion increased from 67% (144/214) in the 6 months prior to COVID to 90% (602/669) in the 6 months during COVID. Nearly all satisfaction questionnaires (99%, 1013/1022) recorded that participants were satisfied with the service. CONCLUSIONS: This direct-to-patient telemedicine service was safe, effective, and acceptable, and supports the claim that there is no medical reason for mifepristone to be dispensed in clinics as required by the Food and Drug Administration. In some cases, participants did not need to visit any facilities to obtain the service, which was critical to protecting patient safety during the COVID-19 pandemic. IMPLICATIONS: Medical abortion using telemedicine and mail is effective and can be safely provided without a pretreatment ultrasound. This method of service delivery has the potential to greatly improve access to abortion care in the United States.

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.

Medical termination for pregnancy in early first trimester (≤ 63 days) using combination of mifepristone and misoprostol or misoprostol alone: a systematic review.

BACKGROUND: A wide range of drugs have been studied for first trimester medical abortion. Studies evaluating different regimens, including combination mifepristone and misoprostol and misoprostol alone regimens, show varying results related to safety, efficacy and other outcomes. Thus, the objectives of this systematic review were to compare the safety, effectiveness and acceptability of medical abortion and to compare medical with surgical methods of abortion ≤63 days of gestation. METHODS: Pubmed and EMBASE were systematically searched from database inception through January 2019 using a combination of MeSH, keywords and text words. Randomized controlled trials on induced abortion at ≤63 days that compared different regimens of medical abortion using mifepristone and/or misoprostol and trials that compared medical with surgical methods of abortion were included. We extracted data into a pre-designed form, calculated effect estimates, and performed meta-analyses where possible. The primary outcomes were ongoing pregnancy and successful abortion. RESULTS: Thirty-three studies composed of 22,275 participants were included in this review. Combined regimens using mifepristone and misoprostol had lower rates of ongoing pregnancy, higher rates of successful abortion and satisfaction compared to misoprostol only regimens. In combined regimens, misoprostol 800 µg was more effective than 400 µg. There was no significant difference in dosing intervals between mifepristone and misoprostol and routes of misoprostol administration in combination or misoprostol alone regimens. The rate of serious adverse events was generally low. CONCLUSION: In this systematic review, we find that medical methods of abortion utilizing combination mifepristone and misoprostol or misoprostol alone are effective, safe and acceptable. More robust studies evaluating both the different combination and misoprostol alone regimens are needed to strengthen existing evidence as well as assess patient perspectives towards a particular regimen.

Slow implementation of mifepristone medical termination of pregnancy in Quebec, Canada: a qualitative investigation.

Objectives: Mifepristone for first-trimester medical termination of pregnancy (MTOP) became available in Quebec in 2018, one year after the rest of Canada. Using the theory of the Diffusion of Innovation (DOI) and the transtheoretical model of change (TTM), we investigated factors influencing the implementation of mifepristone MTOP in Quebec.Material and Methods: Semi-structured interviews were conducted with 37 Quebec physicians in early 2018. Deductive thematic analysis guided by the theory of DOI explored facilitators and barriers to physicians' adoption of mifepristone MTOP. We then classified participants into five stages of mifepristone adoption based on the TTM. Follow-up data collection one year later assessed further adoption.Results: At baseline, three physicians provided mifepristone MTOP (Maintenance) and two were about to start (Action). Thirteen physicians at Preparation and Advanced Contemplation stages intended to start while, within the Slow Contemplation, two intended to start and ten were unsure. Seven had no intention to provide mifepristone MTOP (Pre-Contemplation). Major reported barriers were: complexity of local health care organisations, medical policy restrictions, lack of support, and general uncertainty. One year later, ten physicians provided mifepristone MTOP (including three at baseline) and nine still intended to, while seventeen did not intend to start provision. Seven of sixteen participants (44%) who worked in TOP clinics at baseline were still not providing MTOP with mifepristone one year later.Conclusion: Despite ideological support, mifepristone MTOP uptake in Quebec is slow and laborious, mainly due to restrictive medical policies, vested interests in surgical provision and administrative inertia.

Cost-effectiveness of Mifepristone Pretreatment for the Medical Management of Nonviable Early Pregnancy: Secondary Analysis of a Randomized Clinical Trial.

Importance: Early pregnancy loss (EPL) is the most common complication of pregnancy. A multicenter randomized clinical trial compared 2 strategies for medical management and found that mifepristone pretreatment is 25% more effective than the standard of care, misoprostol alone. The cost of mifepristone may be a barrier to implementation of the regimen. Objective: To assess the cost-effectiveness of medical management of EPL with mifepristone pretreatment plus misoprostol vs misoprostol alone in the United States. Design, Setting, and Participants: This preplanned. prospective economic evaluation was performed concurrently with a randomized clinical trial in 3 US sites from May 1, 2014, through April 30, 2017. Participants included 300 women with anembryonic gestation or embryonic or fetal demise. Cost-effectiveness was computed from the health care sector and societal perspectives, with a 30-day time horizon. Data were analyzed from July 1, 2018, to July 3, 2019. Interventions: Mifepristone pretreatment plus misoprostol administration vs misoprostol alone. Main Outcomes and Measures: Costs in 2018 US dollars, effectiveness in quality-adjusted life-years (QALYs), and treatment efficacy. Incremental cost-effectiveness ratios (ICERs) of mifepristone and misoprostol vs misoprostol alone were calculated, and cost-effectiveness acceptability curves were generated. Results: Among the 300 women included in the randomized clinical trial (mean [SD] age, 30.4 [6.2] years), mean costs were similar for groups receiving mifepristone pretreatment and misoprostol alone from the health care sector perspective ($696.75 [95% CI, $591.88-$801.62] vs $690.88 [95% CI, $562.38-$819.38]; P = .94) and the societal perspective ($3846.30 [95% CI, $2783.01-$4909.58] vs $4845.62 [95% CI, $3186.84-$6504.41]; P = .32). The mifepristone pretreatment group had higher QALYs (0.0820 [95% CI, 0.0815-0.0825] vs 0.0806 [95% CI, 0.0800-0.0812]; P = .001) and a higher completion rate after first treatment (83.8% vs 67.1%; P < .001) than the group receiving misoprostol alone. From the health care sector perspective, mifepristone pretreatment was cost-effective relative to misoprostol alone with an ICER of $4225.43 (95% CI, -$195 053.30 to $367 625.10) per QALY gained. From the societal perspective, mifepristone pretreatment dominated misoprostol alone (95% CI, -$5 111 629 to $1 801 384). The probabilities that mifepristone pretreatment was cost-effective compared with misoprostol alone at a willingness-to-pay of $150 000 per QALY gained from the health care sector and societal perspectives were approximately 90% and 80%, respectively. Conclusions and Relevance: This study found that medical management of EPL with mifepristone pretreatment was cost-effective when compared with misoprostol alone. Trial Registration: ClinicalTrials.gov Identifier: NCT02012491.

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.

Efficacy of mifepristone and misoprostol for medical treatment of missed miscarriage in clinical practice-A cohort study.

INTRODUCTION: It has been estimated that one out of every four women experience first-trimester miscarriage. Missed miscarriage is a common form of early miscarriage where the products of conception are not expelled from the uterus. It is diagnosed by ultrasound. The primary objective of this study was to evaluate the success rate of a combination treatment with mifepristone and misoprostol for missed miscarriage in clinical practice. The secondary objective was to identify significant factors influencing the rate of success. MATERIAL AND METHODS: A cohort of 941 consecutive women with an ICD-10 diagnosis of missed miscarriage who received treatment with 800 µg vaginal misoprostol and 2 repeat doses of 400 µg oral misoprostol after mifepristone pretreatment between 1 January 2012 and 31 December 2014 was analyzed. Women with a uterine size smaller than 12 weeks who were planned for medical treatment were included in the study. The exclusion criteria were primary surgical management or planned follow up outside the Stockholm County Council area. RESULTS: The success rate of medical treatment, defined as no need for surgical treatment, was 85.5% (805/941) in women with a uterine size of less than 12 weeks. However, for women with uterine size below 9 weeks the success rate was 88.9% (586/659). Indeed, uterine size of 9 gestational weeks or larger at time of treatment was identified as the only significant risk factor for surgical intervention. CONCLUSIONS: The medical regimen for missed miscarriage offered in this study appears to be safe and with high rates of success. Conclusions about which women to exclude from medical treatment could not be made. Medical treatment may therefore benefit all women with missed miscarriage who wish to avoid primary surgery.

PURL: Early pregnancy loss: Pretreat with mifepristone?

Yes. While medical management of early pregnancy loss with misoprostol frequently results in treatment failure, pretreating with mifepristone can increase efficacy.

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.

Self-assessment of success of early medical abortion using a self-performed urine pregnancy test.

Purpose: The European Society of Contraception Expert Group on Abortion identified as one of its priorities the need to disseminate up-to-date evidence-based information on the use of urine pregnancy tests by women for the self assessment of the success of early medical abortion (EMA). Methods and materials: A concise communication was produced which summarises the latest research in an easy-to-read format suitable for busy clinicians. Information about individual urinary pregnancy tests is presented in boxes for ease of reference. Results: Urinary pregnancy tests (low sensitivity, high sensitivity and multilevel) can be used in combination with signs and symptoms of pregnancy to exclude an ongoing pregnancy after EMA. Conclusion: Women are able to determine the success of early medical abortion (EMA) themselves using a combination of signs, symptoms and a urine pregnancy test. This simplifies EMA, expands the range of professionals able to provide EMA and most importantly gives women greater control over their bodies and treatment.

Could implementation of mifepristone address Canada's urban-rural abortion access disparity: a mixed-methods implementation study protocol.

INTRODUCTION: In January 2017, mifepristone-induced medical abortion was made available in Canada. In this study, we will seek to (1) understand facilitators and barriers to the implementation of mifepristone across Canada, (2) assess the impact of a 'community of practice' clinical and health service support platform and (3) engage in and assess the impact of integrated knowledge translation (iKT) activities aimed to improve health policy, systems and service delivery issues to enhance patient access to mifepristone. METHODS AND ANALYSIS: This prospective mixed-methods implementation study will involve a national sample of physicians and pharmacists recruited via an online training programme, professional networks and a purpose-built community of practice website. Surveys that explore constructs related to diffusion of innovation and Godin's behaviour change frameworks will be conducted at baseline and at 6 months, and qualitative data will be collected from electronic interactions on the website. Survey participants and a purposeful sample of decision-makers will be invited to participate in in-depth interviews. Descriptive analyses will be conducted for quantitative data. Thematic analysis guided by the theoretical frameworks will guide interpretation of qualitative data. We will conduct and assess iKT activities involving Canada's leading health system and health professional leaders, including evidence briefs, Geographical Information System (GIS)maps, face-to-face meetings and regular electronic exchanges. Findings will contribute to understanding the mechanisms of iKT relationships and activities that have a meaningful effect on uptake of evidence into policy and practice. ETHICS AND DISSEMINATION: Ethical approval was received from the University of British Columbia Children's and Women's Hospital Ethics Review Board (H16-01006). Full publication of the work will be sought in an international peer-reviewed journal. Findings will be disseminated to research participants through newsletters and media interviews, and to policy-makers through invited evidence briefs and face-to-face presentations.