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.).

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.

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 .).

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.

Effect of mifepristone and lithospermum combination regimen on medical abortion in early pregnancy rats.

OBJECTIVE: To investigate the optimal dose of mifepristone and lithospermum combination regimen on medical abortion in early pregnancy rats without increasing side effects. STUDY DESIGN: Sixty sexually mature female Sprague Dawley (SD) rats with early pregnancy were randomly allocated into 10 groups, including a control group (treated with 0.5% CMC-Na) and nine experiments (treated with 1 mg/kg mifepristone, and 90, 180, 270, and 540 mg/kg lithospermum, and 90/180/270/540 mg/kg lithospermum +1 mg/kg mifepristone, respectively). The hormone levels, factors associated with endometrial bleeding, oxidative stress, and apoptotic proteins in the endometrium, were then investigated. RESULTS: The results demonstrated that 540 mg/kg lithospermum plus 1 mg/kg mifepristone treatment significantly improved the abortion rate when compared with the control group. Compared with the 1 mg/kg mifepristone, 540 mg/kg lithospermum plus 1 mg/kg mifepristone treatment did not induce significant increase in factors associated with abnormal endometrial bleeding, such as matrix metalloproteinase-9 (MMP9). However, mifepristone and lithospermum combination regimen promoted the expression level of malondialdehyde (MDA), activated caspase 3, caspase 9 and Bax, meanwhile, reduced the expression of superoxide dismutase (SOD) and Bcl-2. CONCLUSION: These findings provided strong evidence that mifepristone and lithospermum combination regimen can obtain satisfactory abortion effect without increasing the expression level of bleeding-related factors.

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.

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.

Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BACKGROUND: Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 µg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure. OBJECTIVE: This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss. STUDY DESIGN: We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment. RESULTS: Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49). CONCLUSION: No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.

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.

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.

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.

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.

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.

Risk factors for surgical intervention of early medical abortion.

BACKGROUND: By being noninvasive, medical termination of pregnancy has increased worldwide access to abortion and improved safety of unsafe abortion. However, secondary surgical intervention is the most frequent complication to medical abortion. OBJECTIVE: We aimed to identify and quantify risk factors for surgical intervention in women undergoing medically induced termination of pregnancy before 9 completed weeks of gestation. STUDY DESIGN: We conducted a nationwide cohort study, including all pregnancies terminated before 63 gestational days in women aged 15-49 years during the period 2005-2015. Induction regimen was 200 mg mifepristone followed 24-48 hours later by 0.8 mg vaginal misoprostol. All included pregnancies were followed up for 8 weeks from mifepristone administration. Data were retrieved from national health registers. Multiple logistic regression provided adjusted odds ratios of surgical intervention with 95% confidence intervals. The discriminative ability of the risk factors in identifying surgical intervention was assessed by cross-validated area under the receiver operating characteristic curve. RESULTS: Of 86,437 early medical abortions, 5320 (6.2%) underwent a surgical intervention within 8 weeks after induction. The proportion of surgical interventions increased from 3.5% in the 5th to 6th gestational week to 10.3% in week 9, odds ratio, 3.2 (95% confidence interval, 2.9-3.6). Compared with women aged 15-19 years, the risk of surgical intervention increased with increasing maternal age until the age of 30-34 years, odds ratio, 1.7 (95% confidence interval, 1.5-1.9), where after the risk decreased to an odds ratio for age group 40-49 of 1.2 (95% confidence interval, 1.0-1.4). Compared with nulliparous women, a history of only vaginal deliveries with spontaneous delivery of placenta implied an odds ratio of 1.1 (95% confidence interval, 1.0-1.2), women with a history of at least 1 cesarean delivery, an odds ratio of 1.5 (95% confidence interval, 1.3-1.6), and women having experienced a manual removal of placenta after a vaginal birth, an odds ratio of 2.0 (95% confidence interval, 1.7-2.4). Previous medically induced abortion decreased the risk of surgical intervention, odds ratio 0.84 (95% confidence interval, 0.78-0.91), whereas previous early (before 56 days of gestation) surgically induced abortion implied a 53% (95% confidence interval, 1.4-1.7) increased risk of surgical intervention. Previous surgical abortion after 55 days of gestation increased the risk by 17% (95% confidence interval, 1.1-1.3). The area under the receiver operating characteristic curve of the model including all quantified risk factors was 63% (95% confidence interval, 62-64%). CONCLUSION: Gestational age, maternal age, previous deliveries, and history of medically and surgically induced abortions all had a significant influence on the risk of surgical intervention of early medical abortion. However, inclusion of all quantified risk factors still left most interventions unpredictable.

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.

Patients' Motivation for Surgical Versus Medical Abortion.

OBJECTIVE: Induced abortion is the second most common reproductive health procedure in Canada. Among all Canadian women, 31% will have at least one induced abortion in their life. Unfortunately, abortion services are disparate throughout the country. With the recent introduction of mifepristone in Canada, it is hoped that access to abortion will be improved. However, it is recognized that some women who are eligible for medical abortion with mifepristone will still choose surgical abortion. The purpose of this study was to understand the patient's motivation to choose surgical abortion instead of medical abortion. METHODS: A survey was given to a sample of women coming to the Women's Clinic at Kingston General Hospital in Kingston, Ontario, for surgical abortion who qualified for medical abortion at the time their appointment was made. The study was approved by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board before data collection (#6022783) (Canadian Task Force Classification II-2). RESULTS: This study was conducted between February 13, 2018 and June 1, 2018. In agreement with previous studies, the most common perceived advantages of surgical abortion were that it is faster and requires fewer visits. Therefore, one of the greatest perceived obstacles to medical abortion is the need for follow-up. CONCLUSION: Being able to offer two highly effective options for induced abortion will hopefully improve equitable access to abortion. To increase women's acceptance of medical abortion as a feasible option, we need to consider making some changes to the follow-up plan in our clinic.

Dosing interval between mifepristone and misoprostol in second and third trimester termination.

OBJECTIVE: To compare several strategies for second trimester labor induction for termination of pregnancy (TOP) using misoprostol and mifepristone and to determine which one is more effective in accelerating the time to delivery. METHOD: This was a retrospective study in which pregnancies that underwent second and third trimester TOP due to fetal anomalies between 2007 and 2017 were classified into a group that received misoprostol alone, a group that received mifepristone followed by misoprostol on the same day, one where misoprostol was given 1 day after mifepristone and one where the medications were administered 2 days apart. The primary outcome measure was the induction to delivery interval. RESULTS: 481 pregnancies fulfilled the inclusion criteria. In 140 cases, mifepristone was not administered. 341 women received mifepristone prior to induction, which was administered on the day of induction in 85 cases, and 1 or 2 days prior to induction in 140 and 19 cases. Median time interval between first induction and delivery was 15.0 (IQR 10.0-24.1) h in case no mifepristone was given and 13.2 (9.7-18.2) h if mifepristone was given on the same day and 9.3 (6.6-14.9) and 10.5 (7.2-22.3) h, if mifepristone was given 1 or 2 days prior to induction. After 24 h, the proportion of terminated pregnancies in each of the four groups was 75.0, 83.5, 93.2 and 78.9%. CONCLUSION: A 1 day interval between mifepristone and misoprostol is more effective in second and third trimester TOP compared to other strategies in terms of reducing the induction to abortion interval.

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.