Factors Affecting the Success of Repeated Misoprostol Course for the Treatment of Missed Abortion.

OBJECTIVE: To assess the rates of success of the second dose of Misoprostol administration and to evaluate the parameters that affect the success of this approach. STUDY DESIGN: This retrospective cohort study was performed using institutional database of Carmel Medical Center between the dates of 1/11/2012-1/11/2017. Patients with ultrasound proven intrauterine abnormal pregnancy, treated for missed abortion or blighted ovum by two doses of intravaginal Misoprostol were included. The primary outcome was the treatment success rate of repeated Misoprostol treatment, and factors affecting this outcome. RESULTS: Overall, 97 patients were included in the study. The success of repeated dose of Misoprostol was noted in 46 cases (47.4%). A higher success rate was noted in symptomatic women - 64.3% vs. 35.7% in asymptomatic patients (Odds Ratio 2.6, 95% Confidence Interval 1.1-6.5). In addition, marginal significance was noted for pregnancies with an embryonic pulse previously observed (66.7% in the success group vs. 33.3% in failed treatment, p=0.051). DISCUSSION: Efficacy of a repeated Misoprostol course was shown to have a success rate of 47%%. This success rate is slightly increased in women presenting symptoms of bleeding before first administration. This information is highly important in the clinical discussion with each patient prior choosing a possible treatment.

Intravaginal misoprostol versus uterine curettage for missed abortion: A cost-effectiveness analysis.

PURPOSE: To evaluate the cost-effectiveness of a strategy based on direct-acting uterine curettage (UC) versus a pre-direct-acting misoprostol (1600 mg) in patients with missed abortion (MA), from the perspective of a National Health System. METHODS: An open prospective cohort study was carried out at Reina Sofía University Hospital (Córdoba, Spain) from January 1, 2019 to December 31, 2019 in 180 patients diagnosed with MA. The patients chose medical treatment with intravaginal misoprostol (800 µg/4 h) or UC after receiving complete and detailed information. The effectiveness, clinical characteristics of the patients, costs of treating and managing the disease, and satisfaction with the procedures were recorded. RESULTS: One hundred and forty-five patients (80.6%) chose misoprostol versus 35 patients (19.4%) who chose UC. The effectiveness of misoprostol has been 42% evaluated at 48 h; UC success rate has been 100%. The incidence of side effects is significantly higher in patients treated with misoprostol (p < 0.05); as well as the number of care received by the patient (p < 0.05). Satisfaction is higher in patients treated with UC (p < 0.05). However, the cost is almost 5-folds higher in patients treated with UC (p < 0.05). CONCLUSION: UC has a higher success rate, greater satisfaction, and a lower incidence of side effects, although significantly increases the cost compared to misoprostol in MA.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

[Mifepristone in primary care: no impediments against its use in management of missed miscarriage]. / Prescriptie van mifepriston in de eerste lijn?

In the Netherlands, medical treatment to women with a non-vital pregnancy is provided in secondary care. In a Dutch pilot study, it has been shown that treatment of a missed miscarriage with misoprostol in primary care is an acceptable alternative. However, there are clear indications that medical treatment in women with a non-vital pregnancy is greatly improved when mifepristone is prescribed in addition to misoprostol. The authors state that this treatment is also justified in primary care.

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS: MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 µg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS: Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION: Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Effect of misoprostol with and without letrozole on the induction of abortion for women with first-trimester missed abortion.

OBJECTIVE: To determine whether addition of letrozole to a misoprostol-based abortion regimen can increase the rate of complete abortion. METHODS: The randomized, placebo-controlled, double-blind trial enrolled women with missed abortion in the first trimester of pregnancy attending Sadooghi Hospital, Isfahan, Iran, from 2016 to 2018. The women were randomly assigned to the study group, which received 10 mg of letrozole daily for 3 days, followed by two doses of 800 µg of vaginal misoprostol at a 4-hour interval, or the control group, which received a placebo, followed by the same dose of misoprostol. Sonography was performed to check the abortion status. RESULTS: In total, 120 women completed the study: 60 in the misoprostol plus letrozole group, and 60 in the misoprostol only group. Complete abortion was documented for 93 (77.5%) women: 48 (80.0%) in the misoprostol plus letrozole group and 45 (75.0%) in the misoprostol only group (P=0.80). The mean duration of induction in the misoprostol plus letrozole and misoprostol only groups was 7.35 ± 3.54 hours and 8.2 ± 3.8 4hours, respectively (P=0.21). CONCLUSION: Administration of misoprostol alone was found to be as effective as the administration of misoprostol plus letrozole for first-trimester missed abortion.

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 management of first trimester missed miscarriage: the efficacy and complication rate.

Our aim of the study was to evaluate the efficacy and complication rate of our inpatient medical management protocol for missed miscarriages. Three-hundred and ninety women hospitalised at our tertiary centre because of a missed miscarriage/anembryonic pregnancy in 2012-2013 were included in this retrospective study. The women underwent either a low (until 9 + 0 weeks of gestation) or high gestational age (from 9 + 1 until 15 + 6 weeks of gestation) management protocol. The success rate, curettage in the first 48 hours after the procedure, the complication rate and the factors that might influence these outcomes were evaluated. The overall success rate was 83.3%. The curettage in the first 48 hours after the procedure was performed in 7.4% of the patients and was more often in the high gestational age protocol. Complications that required another outpatient visit or hospitalisation occurred in 9% of the patients. Higher beta-hCG values 14 days after the procedure and the absence of evacuation of products of conception during hospitalisation were associated with a higher complication rate. IMPACT STATEMENT What is already known on this subject? As much as 10-20% of clinically recognised pregnancies end in a spontaneous abortion. A missed miscarriage and a blighted ovum represent a form of spontaneous abortion, which has long been treated with surgical evacuation. However, nowadays, medical management represents a well-established alternative with very high success rates and is considered as an equivalent and safe method that is also very well accepted by patients. What do the results of this study add? According to our results, a medical management of a first trimester missed miscarriage and a blighted ovum is very effective with an overall success rate of 83.3% and a very low percentage of curettage in the first 48 hours after the procedure (7.4%). Our study was also able to identify higher beta-hCG values 14 days after procedure and absence of evacuation of products of conception during hospitalisation as risk factors for complication occurrence. What are the implications of these findings for clinical practice and/or further research? Our study helps to identify patients who are at greater risk for developing complications after the medical management of a first trimester missed miscarriage.

Sublingual vs vaginal misoprostol for completion of first trimester missed abortion: a randomised controlled trial.

OBJECTIVE: The study aimed to compare the efficacy and safety of sublingual and vaginal misoprostol for termination of pregnancy in women with first trimester missed abortion. METHODS: A single-blind, parallel group, randomised clinical trial (ClinicalTrials.gov NCT02686840) was conducted in a university hospital between 1 February 2016 and 31 January 2017. All women who presented with first trimester missed abortion were invited to participate in the study and were randomised to one of two groups: one group received sublingual misoprostol in three doses of 800 µg every 4 h, while a second group received vaginal misoprostol in the same dosage regimen. The primary outcome of the study was the rate of complete abortion within 7 days after initiation of treatment. RESULTS: The study included 200 women (100 in each arm). By day 7, successful complete abortion was significantly more frequent in the sublingual misoprostol group (71.4%) than in the vaginal misoprostol group (51.5%) (p = .006). By day 30, the rate of complete abortion was higher in the sublingual misoprostol group (90.6%) than in the vaginal misoprostol group (83.9%), but with no statistically significant difference (p = .164). The mean length of the induction-expulsion interval in the sublingual misoprostol group was significantly shorter compared with the vaginal misoprostol group (12.3 ± 3.1 h vs 16.4 ± 4.2 h, respectively; p = .001) and the sublingual misoprostol group had a smaller drop in haemoglobin level (p = .001). The side effects of misoprostol were significantly more frequent in the sublingual group compared with the vaginal group. CONCLUSION: Sublingual misoprostol is more effective than vaginal misoprostol in completing first trimester missed abortion, with a shorter induction-expulsion time. Sublingual misoprostol is, however, associated with more side effects, such as unpleasant taste, gastrointestinal symptoms and fever, compared with vaginal misoprostol.

Association between uterine position and transvaginal misoprostol treatment for early pregnancy failure.

AIM: We aimed to determine the importance of uterine position as a predicting factor of success rate in medically treated early pregnancy failure (EPF). METHODS: We carried out a retrospective cohort study at the Obstetrics and Gynecology Department of a tertiary medical center between January 2011 and June 2012. We included women diagnosed with EPF, which we defined as women diagnosed with missed abortion up to 13 gestational weeks. Patients were treated with one or two doses of 800 µg of misoprostol vaginally in accordance with the department's protocol. Demographic, clinical, and treatment success data were collected from patient electronic records. RESULTS: A total of 255 women were included in our study. The success rate after treatment with misoprostol for the anterior uterine group was 78.7% as compared to the non-anterior uterine group, which achieved a success rate of 88.1%. This difference was not statistically significant (P = 0.180). In a multivariate analysis comparing patients for whom treatment with misoprostol was successful as opposed to patients for whom treatment failed, only embryonic sac size showed a statistically significant difference, measuring shorter in the success group. CONCLUSION: Uterine position has no effect on success rate of misoprostol treatment for EPF.

Medical Termination of Delayed Miscarriage: Four-Year Experience with an Outpatient Protocol / Terminação médica de gravidez inviável do 1° trimestre: quatro anos de experiência com um protocolo de tratamento em ambulatório

Abstract Purpose To evaluate the efficacy of an outpatient protocol with vaginal misoprostol to treat delayed miscarriage. Methods Retrospective analysis of prospectively collected data on women medically treated for missed abortion with an outpatient protocol. The inclusion criteria were: ultrasound-based diagnosis of missed abortion with less than 10 weeks; no heavy bleeding, infection, inflammatory bowel disease ormisoprostol allergy; nomore than 2 previous spontaneous abortions; the preference of the patient regarding the medical management. The protocol consisted of: 1) a single dose of 800 μg of misoprostol administered intravaginally at the emergency department, after which the patients were discharged home; 2) clinical and ultrasonographic evaluation 48 hours later - if the intrauterine gestational sac was still present, the application of 800 μg of vaginal misoprostol was repeated, and the patients were discharged home; 3) clinical and ultrasonography evaluation 7 days after the initiation of the protocol - if the intrauterine gestational sac was still present, surgical management was proposed. The protocol was introduced in January 2012. Every woman received oral analgesia and written general recommendations. We also gave them a paper form to be presented and filled out at each evaluation. Results Complete miscarriage with misoprostol occurred in 340 women (90.2%). Surgery was performed in 37 (9.8%) patients, representing the global failure rate of the protocol. Miscarriage was completed after the first misoprostol administration in 208 (55.2%) women, with a success rate after the second administration of 78.1% (132/169). The average age of the women with complete resolution using misoprostol was superior to the average age of those who required surgery (33.99 years versus 31.74 years; p = 0.031). Based on the ultrasonographic findings in the first evaluation, the women diagnosed with fetal loss achieved greater success rates compared with those diagnosed with empty sac (p = 0.049). Conclusions We conclude this is an effective and safe option in the majority of delayed miscarriage cases during the first trimester, reducing surgical procedures and their consequences.

Resumo Objetivo Avaliar a eficácia de um protocolo de tratamento médico da gravidez inviável do primeiro trimestre (GI1°T) com misoprostol vaginal em regime de ambulatório. Métodos Análise retrospectiva de dados colhidos prospectivamente de grávidas tratadas com misoprostol vaginal em ambulatório. Os critérios de inclusão foram: diagnóstico de GI1°T com < 10 semanas de gestação; ausência de hemorragia abundante, infeção, doença inflamatória intestinal ou alergia ao misoprostol; 2 abortamentos anteriores; e preferência da paciente por tratamento médico. O protocolo consiste em: dia 0-aplicação demisoprostol intravaginal (800μg) no Serviço de Urgência e alta para o domicílio; dia 2-se persistência de saco gestacional intrauterino, aplicação de segunda dose de misoprostol (800μg) e alta; Dia 7-se persistência de saco gestacional intrauterino, proposto esvaziamento uterino instrumentado. O protocolo foi implementado em janeiro de 2012. Todas as grávidas receberam analgesia oral e informação por escrito com recomendações gerais. Receberam ainda um formulário a ser preenchido em cada vinda à urgência. Resultados Das 377 mulheres incluídas, observou-se abortamento completo em 340 (90,2%). As restantes 37 (9,8%) necessitaram de tratamento cirúrgico - taxa de falência global do protocolo. Em 208 (55,2%), o sucesso foi observado ao fim da 1ª dose, com uma taxa de eficácia da 2ª dose de 78,1% (132/169). A idade média das mulheres com sucesso do tratamento médico foi superior à das mulheres sem sucesso do mesmo (33,99 versus 31,74 anos; p = 0,031). O sucesso do tratamento foi maior quando o diagnóstico ecográfico inicial era de um embrião sem vitalidade comparado com os casos de ovo anembrionado (p = 0.049). Conclusões Conclui-se que esta é uma opção de tratamento eficaz e segura na maioria das situações de GI1°T, evitando a necessidade de internamento e de intervenção cirúrgica.

Medical Termination of Delayed Miscarriage: Four-Year Experience with an Outpatient Protocol.

Purpose To evaluate the efficacy of an outpatient protocol with vaginal misoprostol to treat delayed miscarriage. Methods Retrospective analysis of prospectively collected data on women medically treated for missed abortion with an outpatient protocol. The inclusion criteria were: ultrasound-based diagnosis of missed abortion with less than 10 weeks; no heavy bleeding, infection, inflammatory bowel disease or misoprostol allergy; no more than 2 previous spontaneous abortions; the preference of the patient regarding the medical management. The protocol consisted of: 1) a single dose of 800 µg of misoprostol administered intravaginally at the emergency department, after which the patients were discharged home; 2) clinical and ultrasonographic evaluation 48 hours later - if the intrauterine gestational sac was still present, the application of 800 µg of vaginal misoprostol was repeated, and the patients were discharged home; 3) clinical and ultrasonography evaluation 7 days after the initiation of the protocol - if the intrauterine gestational sac was still present, surgical management was proposed. The protocol was introduced in January 2012. Every woman received oral analgesia and written general recommendations. We also gave them a paper form to be presented and filled out at each evaluation. Results Complete miscarriage with misoprostol occurred in 340 women (90.2%). Surgery was performed in 37 (9.8%) patients, representing the global failure rate of the protocol. Miscarriage was completed after the first misoprostol administration in 208 (55.2%) women, with a success rate after the second administration of 78.1% (132/169). The average age of the women with complete resolution using misoprostol was superior to the average age of those who required surgery (33.99 years versus 31.74 years; p = 0.031). Based on the ultrasonographic findings in the first evaluation, the women diagnosed with fetal loss achieved greater success rates compared with those diagnosed with empty sac (p = 0.049). Conclusions We conclude this is an effective and safe option in the majority of delayed miscarriage cases during the first trimester, reducing surgical procedures and their consequences.

Objetivo Avaliar a eficácia de um protocolo de tratamento médico da gravidez inviável do primeiro trimestre (GI1°T) com misoprostol vaginal em regime de ambulatório. Métodos Análise retrospectiva de dados colhidos prospectivamente de grávidas tratadas com misoprostol vaginal em ambulatório. Os critérios de inclusão foram: diagnóstico de GI1°T com < 10 semanas de gestação; ausência de hemorragia abundante, infeção, doença inflamatória intestinal ou alergia ao misoprostol; ≤ 2 abortamentos anteriores; e preferência da paciente por tratamento médico. O protocolo consiste em: dia 0­aplicação de misoprostol intravaginal (800µg) no Serviço de Urgência e alta para o domicílio; dia 2­se persistência de saco gestacional intrauterino, aplicação de segunda dose de misoprostol (800µg) e alta; Dia 7­se persistência de saco gestacional intrauterino, proposto esvaziamento uterino instrumentado. O protocolo foi implementado em janeiro de 2012. Todas as grávidas receberam analgesia oral e informação por escrito com recomendações gerais. Receberam ainda um formulário a ser preenchido em cada vinda à urgência. Resultados Das 377 mulheres incluídas, observou-se abortamento completo em 340 (90,2%). As restantes 37 (9,8%) necessitaram de tratamento cirúrgico ­ taxa de falência global do protocolo. Em 208 (55,2%), o sucesso foi observado ao fim da 1ª dose, com uma taxa de eficácia da 2ª dose de 78,1% (132/169). A idade média das mulheres com sucesso do tratamento médico foi superior à das mulheres sem sucesso do mesmo (33,99 versus 31,74 anos; p = 0,031). O sucesso do tratamento foi maior quando o diagnóstico ecográfico inicial era de um embrião sem vitalidade comparado com os casos de ovo anembrionado (p = 0.049). Conclusões Conclui-se que esta é uma opção de tratamento eficaz e segura na maioria das situações de GI1°T, evitando a necessidade de internamento e de intervenção cirúrgica.

Misoprostol for medical treatment of missed abortion: a systematic review and network meta-analysis.

The efficacy and safety of misoprostol alone for missed abortion varied with different regimens. To evaluate existing evidence for the medical management of missed abortion using misoprostol, we undertook a comprehensive review and meta-analysis. The electronic literature search was conducted using PubMed, the Cochrane Library, Embase, EBSCOhost Online Research Databases, Springer Link, ScienceDirect, Web of Science, Ovid Medline and Google Scholar. 18 studies of 1802 participants were included in our analysis. Compared with vaginal misoprostol of 800 ug or sublingual misoprostol of 600 ug, lower-dose regimens (200 ug or 400 ug) by any route of administration tend to be significantly less effective in producing abortion within about 24 hours. In terms of efficacy, the most effective treatment was sublingual misoprostol of 600 ug and the least effective was oral misoprostol of 400 ug. In terms of tolerability, vaginal misoprostol of 400 ug was reported with fewer side effects and sublingual misoprostol of 600 ug was reported with more side effects. Misoprostol is a non-invasive, effective medical method for completion of abortion in missed abortion. Sublingual misoprostol of 600 ug or vaginal misoprostol of 800 ug may be a good choice for the first dose. The ideal dose and medication interval of misoprostol however needs to be further researched.

Utility of ßhCG monitoring in the follow-up of medical management of miscarriage.

OBJECTIVE: To evaluate the percentage change in total ßeta-unit human chorionic gonadotropin (ßhCG) levels (%ΔßhCG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13 weeks. METHODS: A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total ßhCG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound (TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %ΔßhCG ((baseline ßhCG - follow-up ßhCG)/baseline ßhCG × 100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. RESULTS: %ΔßhCG was calculated for cases with ßhCG levels within two days of misoprostol and TVUS; calculation interval determined case number. The median %ΔßhCG for 24 cases with a persistent sac (6-9 day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% (IQR: 95.44-98.43); P < 0.0001). The median %ΔßhCG for eight cases needing surgery on clinical criteria (5-9 day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% (IQR: 64.63-91.15; maximum 94.06) vs 97.68% (IQR: 95.61-98.50); P < 0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %ΔßhCG > 87% predicted no sac at TVUS. %ΔßhCG > 94.5% predicted no surgery on clinical criteria. CONCLUSION: %ΔßhCG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage.

Sublingual misoprostol for management of empty sac or missed miscarriage: The first two years' experience at a metropolitan Australian hospital.

BACKGROUND: Misoprostol management of miscarriage is only now becoming widely used in Australia. AIMS: To review the efficacy, safety and the popularity of outpatient sublingual misoprostol in empty sac/missed miscarriage management over its first two years of availability in a metropolitan Australian hospital. MATERIALS AND METHODS: A retrospective cohort review was undertaken of women choosing sublingual misoprostol 600 µg (three tablets) × three doses for miscarriage management. Principal outcomes assessed were miscarriage resolution without the need for curettage and complications. Additionally, the relative popularity of misoprostol versus surgery by place of birth and over time, and the return of pregnancy tissue for histology were analysed. RESULTS: Between 1 December 2012 and 30 November 2014, 279 women chose sublingual misoprostol for nonurgent miscarriage management, while 420 chose surgery (40 and 60%, respectively). Of the misoprostol cohort, 269 had complete data; 239 of 269 (88.8%) had resolution without curettage, nine (3.3%) had acute curettage, 21 (7.8%) had nonacute curettage, 30 (11.15%) had unplanned emergency department presentation, 11 (4.1%) had unplanned admission, three (1.1%) had blood transfusion and one (0.4%) had an infection requiring admission. Misoprostol was as popular with Australian-born as overseas-born women; 53.5% of patients returned histopathology specimens; one (0.7%) demonstrated partial hydatidiform mole. CONCLUSIONS: Outpatient management of missed/empty gestational sac miscarriage using sublingual misoprostol is associated with a high rate of avoiding curettage and the low rate of complication. It is equally popular with Australian-born and overseas-born women. Just over 50% returned pregnancy tissue for analysis.

Serum biomarkers may help predict successful misoprostol management of early pregnancy failure.

In order to simplify management of early pregnancy loss, our goal was to elucidate predictors of successful medical management of miscarriage with a single dose of misoprostol. In this secondary analysis of data from a multicenter randomized controlled trial, candidate biomarkers were compared between 49 women with missed abortion who succeeded in passing their pregnancy with a single dose of misoprostol and 46 women who did not pass their pregnancy with a misoprostol single dose. We computed the precision of trophoblastic protein and hormone concentrations to discriminate between women who succeed or fail single dose misoprostol management. We also included demographic factors in our analyses. We found overlap in the concentrations of the individual markers between women who succeeded and failed single-dose misoprostol. However, hCG levels ≥ 4000 mIU/mL and ADAM-12 levels ≥ 2500 pg/mL were independently associated with complete uterine expulsion after one dose of misoprostol in our population. A multivariable logistic model for success included non-Hispanic ethnicity and parity <2 in addition to hCG ≥ 4000 mIU/mL and ADAM-12 ≥ 2500 pg/mL and had an area under the receiver operating characteristic (ROC) of 0.81 (95% confidence interval: 72-90%). Categorizing women with a predicted probability of ≥ 0.65 resulted in a sensitivity of 75.0%, specificity 77.1% and positive predictive value of 81.8%. While preliminary, our data suggest that serum biomarkers, especially when combined with demographic characteristics, may be helpful in guiding patient decision-making regarding the management of early pregnancy failure (EPF). Further study is warranted.

Efectividad del tratamiento médico con misoprostol según dosis administrada en aborto retenido menor de 12 semanas / Effectiveness of medical treatment with misoprostol as abortion retained dose administered in less than 12 weeks

Antecedentes: El manejo terapéutico del aborto retenido consiste en evacuar la cavidad uterina espontáneamente o utilizando misoprostol previo al legrado quirúrgico. Objetivo: Evaluar la necesidad de dilatación mecánica post maduración cervical con misoprostol y la tasa de perforación uterina post legrado, utilizando diferentes dosis de misoprostol en pacientes con diagnóstico de aborto retenido menor a 12 semanas. Métodos: Se registraron datos demográficos y ginecológicos de una cohorte retrospectiva de pacientes con diagnóstico de aborto retenido menor a 12 semanas, entre enero de 2008 y diciembre de 2010. Se establecieron 3 grupos de trabajo según la dosis de misoprostol administrada vía vaginal, siendo de 100 (n=131), 200 (n=231) y 400 micrones (n=230), y se observaron las complicaciones asociadas al procedimiento. Resultados: La necesidad de dilatación mecánica fue significativamente mayor en el grupo que recibió 100 micrones de misoprostol al compararlo con el de 200 micrones y 400 micrones (p<0,01). No hubo diferencias estadísticamente significativas entre las que recibieron 200 versus 400 micrones de misoprostol. No hubo diferencias significativas respecto a perforación uterina. Conclusión: En el aborto retenido menor a 12 semanas, la necesidad de dilatación mecánica post maduración cervical, es menor si se utiliza 200 o 400 micrones de misoprostol, sin diferencias en la tasa de perforación uterina.

Background: The therapeutic management of missed abortion consists on evacuating the uterine cavity, spontaneously or by administration of misoprostol previous to curettage. Objectives: Evaluate the need of mechanical dilatation after cervical maturation with misoprostol and the rate of uterine perforation before curettage, using different doses of misoprostol in patients with diagnosis of missed abortion before 12 weeks. Methods: Demographic and gynecologic data were registered of a retrospective cohort of patients with the diagnosis of missed abortion before 12 weeks, between January 2008 and December 2010. Three groups were established according to the dose of misoprostol: 100 (n=131), 200 (n=231) and 400 microns (n=230). Complications associated to the procedure were observed. Results: The need of mechanical dilatation was significant higher for the group with 100 microns of misoprostol in comparison with 200 and 400 microns (p<0.001). There was no statistical significance among who received 200 versus 400 microns of misoprostol. No statistical significance was found for uterine perforation. Conclusion: In the missed abortion before 12 week, the need of mechanical dilatation is lower with 200 or 400 microns of misoprostol, without difference in uterine perforation rate.

The medical management of missed miscarriage: outcomes from a prospective, single-centre, Australian cohort.

OBJECTIVE: To report the prospective outcomes of medical management of missed miscarriage before 13 weeks' gestation from an Australian cohort. DESIGN: Descriptive study of a cohort selected out of a randomised controlled trial. SETTING: Outpatient management at a maternity hospital between 1 May 2007 and 28 July 2010. PARTICIPANTS: 264 women requesting medical management of missed miscarriage. MAIN OUTCOME MEASURES: Number of doses of misoprostol required, unscheduled visits for care, findings at ultrasound follow-up, requirement for surgical management, number of cases of gestational trophoblastic disease (GTD), and self-reported patient experience. RESULTS: 107 women (40.5%) received a repeat dose of misoprostol, and 79 women (29.9%) made unscheduled visits for care. Among the 241 women with Day 7 ultrasound follow-up, a gestational sac was found in 32 women (13.3%), indicating failure of medical management. Complete miscarriage was induced without the need for surgery in 206 women (78.0%). Surgery was performed as an emergency in 13 women (4.9%). Twelve women (4.5%) had surgery for ongoing bleeding after medical management, and four of these did not have chorionic villi on histopathological examination. Five women (1.9%) had GTD, which was managed incidentally under the protocol. Among those who returned patient questionnaires, 73.0% participants (116/159) indicated that they would recommend medical management of miscarriage to other women, while 18.2% (29/159) indicated that they would undergo surgery next time. CONCLUSION: The medical management of missed miscarriage on an outpatient basis is safe and effective. TRIAL REGISTRATION: ACTRN12612000150842.

The association between serum progesterone and outcome of medical management of early fetal demise: a pilot study.

The study objective was to determine the relationship between serum progesterone level and the outcome of mifepristone-misoprostol regimen for medical management of missed miscarriage up to 12 weeks. A blood sample was collected just before mifepristone administration for serum progesterone assay. After 48 h, misoprostol 800 µg was administered vaginally; further 400 µg was administered 4 h later if necessary. Treatment was classed as a success if retained tissues were expelled within 72 h (Group 1), and a failure if this did not occur (Group 2). Of 52 analysed cases, complete medical evacuation occurred within 72 h in 40 (76.9%) women (serum progesterone ranged 13-90 nmol/l). Serum progesterone between the two groups were statistically significant (p < 0.001), by Mann-Whitney test. Of the 12 patients who did not respond, nine (75%) women had serum progesterone < 10 nmol/l. We found mifepristone-misoprostol regimen is less effective in missed miscarriage when serum progesterone is < 10 nmol/l.

Efficacy of misoprostol in relation to uterine position in the treatment of early pregnancy failure.

OBJECTIVE: To evaluate the efficacy of misoprostol in the treatment of missed or incomplete abortion in relation to uterine position. METHODS: In a retrospective cohort study, misoprostol was evaluated as first-line treatment for missed and incomplete abortion before 13 gestational weeks. Between 2009 and 2011, women received 600 µg of sublingual misoprostol for missed abortion or 400 µg for incomplete abortion. Follow-up examinations were performed 7-10 days later, with the option of a second administration of misoprostol. Success was defined by the absence of vaginal bleeding or sonographic signs of incomplete abortion, and falling levels of ß-human chorionic gonadotropin. RESULTS: In total, 111 women were included in the study. A single-dose regimen was effective for 73 (65.8%) women. The overall success rate, including repeat doses, was 73.0% (81/111). There were no significant differences in treatment success between women with missed abortion and those with incomplete abortion (56/89 [62.9%] vs 18/22 [81.8%]; P=0.152). Anteverted uterine position was associated with significantly higher success rates compared with diverging position (62/86 [72.1%] vs 4/18 [22.2%]; P=0.001). CONCLUSION: Misoprostol is an effective treatment for early pregnancy failure. Uterine position might impact the success of medical treatment for missed abortion.