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.

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.

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.

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.

Perda gestacional retida: tratamento baseado em evidência / Missed miscarriage: treatment based on evidence

A perda gestacional é a complicação mais comum da gestação, a qual acarreta sérias repercussões sociais, psicológicas e clínicas para as pacientes. Perda gestacional retida é definida como a visualização do saco gestacional vazio até a décima segunda semana de gestação, gestação intrauterina no primeiro trimestre com perda da atividade cardíaca ou a estabilização da medida comprimento crânio-nádega (CCN) em avaliações ecográficas sucessivas. Historicamente, a conduta cirúrgica tem sido o tratamento de escolha para esse quadro clínico. No entanto, há novas tendências baseadas em estudos recentes que sugerem alternativas terapêuticas válidas como a conduta expectante ou a conduta farmacológica. Esta revisão apresentou a evidência científica atual das diferentes possibilidades de tratamento da perda gestacional, sua eficácia e a relação com possíveis complicações.

Miscarriage is the most common complication of pregnancy which causes serious social, psychological and clinical consequences for patients. Missed miscarriage is defined as the visualization of a gestational sac empty until 12th week of pregnancy, 1st trimester intrauterine pregnancy with loss of heart activity or stabilization of the cranial-rump length measurement (CRL) in successive sonographic evaluations. Historically the surgical approach has been the treatment of choice for this clinical event. However, the new trends based on recent studies suggest that alternative therapies are valid as expectant treatment or pharmacological treatment. This review presented the current scientific evidence of the different possibilities for the treatment of pregnancy loss, its efectiveness and relation to possible complications.

Early pregnancy failure: factors affecting successful medical treatment.

BACKGROUND: The results of medical treatment for early pregnancy failure are conflicting. OBJECTIVES: To determine whether gestational sac volume measurement as well as other variables can predict the success rate of medical treatment for early pregnancy failure. METHODS: The study group comprised 81 women diagnosed with missed abortion or anembryonic pregnancy who consented to medical treatment. Demographic data were collected and beta-human chorionic gonadotropin level was documented. Crown-rump length and the sac volume were measured using transvaginal ultrasound. TVU was performed 12-24 hours after intravaginal administration of 800 micro g misoprostol. If the thickness of the uterine cavity was less than 30 mm, the women were discharged. If the sac was still intact or the thickness of the uterine cavity exceeded 30 mm, they were offered an additional dosage of intravaginal misoprostol or surgical uterine evacuation. RESULTS: Medical treatment successfully terminated 32 pregnancies (39.5%), 30 after one dose of misoprostol and 2 after two doses (group A); 49 underwent surgical evacuation (group B), 47 following one dose of misoprostol and 2 following two doses. There were no significant differences between the groups in age and gestational week. Gestational sac volume did not differ between groups A and B (10.03 and 11.98 ml respectively, P = 0.283). Parity (0.87 and 1.43, P = 0.015), previous pregnancies (2.38 and 2.88, P = 0.037), and betahCG concentration (6961 and 28,748 mlU, P = 0.013) differed significantly between the groups. CONCLUSIONS: Gestational sac volume is not a predictor of successful medical treatment for early pregnancy failure. Previous pregnancies and deliveries and higher betahCG concentration negatively affect the success rate of medical treatment.

Ultrasonographic endometrial thickness after medical and surgical management of early pregnancy failure.

OBJECTIVE: We sought to compare endometrial thickness after misoprostol or dilation and curettage (D&C) for early pregnancy failure and to assess the predictive value of endometrial thickness for subsequent D&C after misoprostol treatment. METHODS: In a randomized trial of early pregnancy failure management, 491 women were treated with misoprostol vaginally, and 161 were treated with D&C. Transvaginal ultrasonography was planned for 2 and 14 days after misoprostol treatment, and 14 days after D&C. RESULTS: The mean endometrial thickness 14 days after treatment was 9.0 mm for the misoprostol group and 6.9 mm for the D&C group, (difference 2.1 mm, 95% confidence interval [CI] 1.0-3.2). After the ultrasonograms 2 and 14 days after misoprostol, 13 (3.8%) and 12 (3.2%) women, respectively, subsequently underwent D&C. Women requiring D&C after successful expulsion had significantly greater endometrial thickness than those who did not at 2 days (mean difference 5.2 mm, 95% CI 1.6-8.8) and 14 days (mean difference 5.5 mm, 95% CI 2.3-8.8) after misoprostol. However, endometrial thickness was a poor predictor of subsequent D&C. The areas under the receiver operating characteristic curves for endometrial thickness at 2 and 14 days were 0.71 and 0.73, respectively. Regardless of cutoff values used for predicting subsequent D&C, endometrial thickness had a positive predictive value of 40% or less. CONCLUSION: The difference in endometrial thickness between misoprostol treatment and D&C for early pregnancy failure is not clinically significant. Endometrial thickness is not a useful predictor of subsequent surgical intervention after successful expulsion of the gestational sac after misoprostol for early pregnancy failure. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,www.clinicaltrials.gov, NCT00177333 LEVEL OF EVIDENCE: I.

Vaginal misoprostol in the management of first-trimester missed abortions.

OBJECTIVE: To evaluate the efficacy of a regimen of vaginal misoprostol in causing the complete expulsion of first-trimester missed abortions, or alternatively dilating the cervix for surgical evacuation. METHOD: Seventy-four women with a transvaginal ultrasound diagnosis of a first-trimester missed abortion and no more than slight vaginal bleeding were consecutively enrolled. Misoprostol (600 microg) was administered vaginally and repeated 4 h later if necessary. Surgical evacuation was performed when complete expulsion was not documented on the ultrasound 10-12 h after treatment. RESULTS: Complete medical evacuation occurred in 42 women (56.8%), 11 (14.9%) of which required only one dose. Seventy women (94.6%) experienced abdominal pain, 73 (98.6%) vaginal bleeding, 10 (13.5%) nausea, 4 (5.4%) vomiting, 5 (6.8%) diarrhea, and 4 (5.4%) transient hyperthermia. There was one case of heavy vaginal bleeding requiring emergency surgical evacuation, and one re-admission for incomplete abortion at 30 days. All but 4 (5.4%) women had permeable cervices at the time of surgery. CONCLUSION: The described regimen of vaginal misoprostol is safe and reasonably effective in inducing complete evacuation in missed abortions. When this does not occur, it almost always provides adequate cervical dilatation for surgery.

Misoprostol en el manejo del aborto retenido y óbito fetal / Misoprostol in the management of missed abortion and fetal death

Se evalúa en forma prospectiva la acción del misoprostol en el manejo del aborto no séptico del primer trimestre (52 abortos retenidos y 13 huevos anembrionados) y en el óbito fetal de segundo trimestre (11 pacientes). Los compromisos de misoprostol de 200 microgramos se colocaron en la vagina y/o endocervix en 1 a 4 dosis (1 dosis por día) en un total de 76 pacientes, hospitalizados en el Servicio de Obstetricia y Ginecología del Hospital del Salvador en el período comprendido entre el 1 de Septiembre de 1995 y el 29 de Febrero de 1996. En 56 de los 76 pacientes (73,7 porciento) se desencadenó y se completó el trabajo de aborto. En las restantes 20 hubo modificaciones significativas del cuello uterino que hicieron notablemente más fácil la dilatación y vaciamiento. No hubo complicaciones atribuibles al método. Se concluye que el misoprostol puede formar parte del arsenal terapéutico en el manejo del aborto retenido y del óbito fetal por la comodidad, seguridad, economía y eficacia de su uso

Pre-operative cervical preparation before first trimester missed abortion: a randomized controlled comparison between single or double intracervical administration of PGE2 gel.

The aim of this study was to evaluate whether a single intracervical application of prostaglandin E2 (PGE2) gel is as effective as a repeated administration with respect to the % of curettage for a missed abortion and to incidence of side effects. 32 consecutive patients with ultrasonographic diagnosis of missed abortion from 6th-13th week of gestation were randomly allocated to either single (group A) or repeated, 2 h apart (group B), intracervical application of PGE2 gel. No differences were observed in cervical dilatation before the administration of the gel between the two groups. In group B, evaluation of cervical dilatation 2 h after the first administration of PGE2 gel and before the second one did not show significant changes as compared to baseline values. The degree of cervical dilatation before surgery was significantly improved as compared to the initial dilatation in both groups; no significant difference was observed between the two study groups. A single administration of PGE2 gel followed by surgery 5 h later has the same effectiveness on cervical dilatation but fewer side effects than repeated administration of the drug 2 h apart.

Periovular: método válido para la interrupción del embarazo no viable de 2§-3§ trimestre / Periovular: accepted method for the non viable pregnancy interruption of 2§-3§ trimester

Se inducen 41 pacientes gestantes, con fetos muertos entre la 24 y 40 semanas de embarazo, mediante la administración extraamniótica de soluciones salinas isotónicas. El éxito fue de 90 por ciento de partos vaginales. Las complicaciones fueron 9,7 por ciento

Experiencia con prostaglandinas E2 en gel intracervicales y tabletas intravaginales en óbitos fetales / Experience with E2 prostaglandins in intracervical gel and intravaginal pills in death fetus

Se presenta nuestra experiencia clínica con el uso de prostaglandinas E2 en gel intracervicales y en tabletas intravaginales en la inducción del parto o abortos en fetos muertos. Considerados globalmente las 50 pacientes, el éxito fue de 70 por ciento, excluídos los 9 casos de fetos acráneos; esta proporción de éxito asciende a 77,7 por ciento en los casos de aborto retenido y a 78,26 por ciento en los casos de feto muerto in utero

Necessidade discutível de esvaziamento uterino de rotina em abortamento espontâneo em clínica privada / Discussible need of routine uterine emptying in spontaneous abortion in private clinic

Os autores apresentam 410 casos de abortamento espontâneos em clínica de esterilidade conjugal, dos quais apenas 32 (7,8//) necessitaram esvaziamento uterino cirúrgico. Destes 9 (nove) obedecendo protocolo da fertilizaçäo assistida com transferência de embriäo, e tendo evoluído para o abortamento. Oito (n=8) por suspeita de manuseio ginecológico, cinco (n=5) por suspeita de mola hidatiforme, nove (n=9) por fatores psicossomáticos envolvidos e apenas um (n=1) devido a sangramenteo uterino abundante. As eliminaçöes espontâneas (n=378) e "loquiaçöes" ocorreram em prazo máximo de 4 semanas näo ocorrendo qualquer complicaçäo neste grupo, levando em consideraçäo que näo houve exame ginecológico em momento algum. A administraçäo de medicamentos estro-progestativos e uterolíticos durante a gestaçäo näo mudaram a evoluçäo. Discutem os autores a necessidade de dosagem de beta-HCG e exames ecográficos frequentes, principalmente visando excluir neoplasia trofoblástica gestacional, e além disso, de boa relaçäo médico-paciente. Acreditam estarem evitando assim "stress" físico local, emocional e complicaçöes dos fatores de abortamentos espontâneos de repetiçäo ou näo pré-existentes. Resta considerar os problemas em adaptar-se esta conduta ás condiçöes dos serviços-escolas ou ambulatórios ginecológicos gerais. Neles, o atendimento médico tem características peculiares quanto a relato médico-paciente, além dos problemas nas repetiçöes de exames instrumentais e laboratoriais. Em trabalho em evoluçäo em nosso ambulatório-escola discute-se estes aspectos