The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT.

OBJECTIVES: To evaluate the efficacy of combined mifepristone and misoprostol compared to misoprostol alone in outpatient medical treatment of first trimester miscarriage. Additionally, the study intends to compare the rate of complications, adverse effects, and treatment acceptability between groups. STUDY DESIGN: Single-center double-blind randomized placebo-controlled trial including women with diagnosis of missed first trimester miscarriage up to 9 weeks of gestation. RESULTS: Between April 2019 and November 2021, 216 women diagnosed with first trimester miscarriage up to 9 weeks of gestation were randomly assigned to mifepristone group or to misoprostol-alone group. Data from 105 women in mifepristone group and 103 women in misoprostol-alone group were analyzed, with no differences in baseline characteristics. The median time between medications (oral mifepristone/placebo and vaginal misoprostol) was nearly 43 h in both groups (p = 0.906). The median time to first follow-up was 2.6 weeks (IQR 1.0) in mifepristone group and 2.4 weeks (IQR 1.0) in misoprostol-alone group (p = 0.855). The overall success rate of medical treatment was significantly higher in the mifepristone-group comparing to misoprostol-alone group (94.3% vs. 82.5%, RR 1.14, 95% CI, 1.03-1.26; p = 0.008). Accordingly, the rate of surgical treatment was significantly lower in the mifepristone-group (5.7% vs.14.6%, RR 0.39, 95% CI, 0.16-0.97; p = 0.034). The composite complication rate was similar and lower than 4% in both groups. No case of complicated pelvic infection, hemodynamic instability or inpatient supportive treatment was reported. There were no significant differences in the rates of adverse events, median score for vaginal bleeding intensity or analgesics use. Despite the same median value, the score of abdominal pain intensity was significantly higher in the mifepristone-group (p = 0.011). In both groups, more than 65% of the women classified the treatment as "good" and 92% would recommend it to a friend on the same clinical situation. CONCLUSION: The mifepristone plus vaginal misoprostol combined treatment for medical resolution of first trimester miscarriage resulted in significant higher success rate and lower rate of surgical uterine evacuation comparing to misoprostol-alone treatment, with no relevant differences in adverse events or treatment acceptability.

Junctional Zone in Infertile Women: A Three-dimensional Ultrasound Study.

OBJECTIVE: To analyze the interobserver and intraobserver reproducibility of the visualization and continuity of the juncional zone (JZ) by three-dimensional (3D) ultrasound in infertile women, and to evaluate the sociodemographic, hormonal, and structural factors that influence these assessments. METHODS: A prospective study conducted at the Assisted Reproductive Technology Unit of Hospital Senhora da Oliveira, in the city of Guimarães, Portugal. Transvaginal 3D ultrasonography was performed, and 2 volumes were generated per case. Two observers who were blinded to each other's work analyzed these volumes, choosing the best coronal section. Four months later, one of the observers performed the same methodology. The JZ visualization was classified as optimal, satisfactory, and unsatisfactory, and the JZ continuity, as continuous and discontinuous. The interobserver and intraobserver agreements were analyzed. The influence of hormonal, structural, and sociodemographic factors on the JZ was evaluated. RESULTS: In total, 65 women were included in the present study. The interobserver reproducibility was substantial for JZ visualization and continuity (k = 0.635 and 0.753 respectively), and the intraobserver reproducibility was very good for JZ visualization and continuity (k = 0.884 and 0.816 respectively). Trilaminar endometrial pattern was associated with optimal JZ visualization (p = 0.012). The increase of 1 unit in the level of serum estradiol represents a 9.9% decrease in the odds of unsatisfactory visualization of the JZ (odds ratio [OR] = 0.9; 95% confidence interval [95%CI] = 0.814-0.996; p = 0.042). Endometriosis increases the odds of unsatisfactory visualization by 24 times (OR = 23.7; 95%CI = 1.262-437.057; p = 0.034). The prevalence of discontinuous JZs was of 60%. Myomas and endometriosis were associated with discontinuous JZs (p = 0.034 and 0.016 respectively). CONCLUSION: The assessment of JZ visualization and continuity by 3D ultrasound is reproducible enough to be used in the clinical practice.

OBJETIVO: Analisar a reprodutibilidade inter e intraobservador da visualização e continuidade da zona juncional (ZJ) por ecografia tridimensional (3D) em mulheres inférteis, e avaliar os fatores sociodemográficos, hormonais e estruturais que afetam essas avaliações. MéTODOS: Um estudo prospectivo conduzido no Centro de Procriação Medicamente Assistida do Hospital Senhora da Oliveira, em Guimarães, Portugal. Foi realizada ecografia transvaginal 3D e gerados 2 volumes por caso. Dois observadores, cegos às avaliações um do outro, analisaram os volumes obtidos e escolheram o melhor corte coronal. Após quatro meses, a mesma análise foi realizada por um dos observadores. A visualização da ZJ foi classificada como ótima, satisfatória e não satisfatória, e a continuidade, como contínua ou descontínua. Foram avaliadas as reprodutibilidades inter e intraobservador. A influência de fatores sociodemográficos, hormonais e estruturais na ZJ foi analisada. RESULTADOS: No total, 65 mulheres foram incluídas no presente estudo. A reprodutibilidade interobservador foi substancial para a visualização e continuidade da ZJ (k = 0,635 e 0,753, respetivamente). A reprodutibilidade intraobservador foi muito boa para a visualização e continuidade da ZJ (k = 0,884 e 0,816, respetivamente). Endométrio trilaminar associou-se à visualização ótima da ZJ (p = 0.012). O aumento de 1 unidade no nível de estradiol diminuiu a chance de visualização não satisfatória da ZJ em 9,9% (razão de probabilidades [RP] = 0,9; intervalo de confiança de 95% [CI95%] = 0,814­0,996; p = 0,042). Endometriose aumentou a chance de visualização não satisfatória da ZJ em 24 vezes (RP = 23,7; CI95% = 1,262­437,057; p = 0,034). A prevalência de ZJs descontínuas foi de 60%. Miomas e endometriose associaram-se a ZJs descontínuas (p = 0,034 e 0,016, respetivamente). CONCLUSãO: A avaliação da visualização e continuidade da ZJ por ecografia 3D é reprodutível, podendo ser utilizada na prática clínica.

Junctional zone in infertile women: a three-dimensional ultrasound study / Zona juncional em mulheres inférteis: estudo por ecografia tridimensional

Abstract Objective To analyze the interobserver and intraobserver reproducibility of the visualization and continuity of the juncional zone (JZ) by three-dimensional (3D) ultrasound in infertile women, and to evaluate the sociodemographic, hormonal, and structural factors that influence these assessments. Methods A prospective study conducted at the Assisted Reproductive Technology Unit of Hospital Senhora da Oliveira, in the city of Guimarães, Portugal. Transvaginal 3D ultrasonography was performed, and 2 volumes were generated per case. Two observers who were blinded to each other's work analyzed these volumes, choosing the best coronal section. Four months later, one of the observers performed the same methodology. The JZ visualization was classified as optimal, satisfactory, and unsatisfactory, and the JZ continuity, as continuous and discontinuous. The interobserver and intraobserver agreements were analyzed. The influence of hormonal, structural, and sociodemographic factors on the JZ was evaluated. Results In total, 65 women were included in the present study. The interobserver reproducibility was substantial for JZ visualization and continuity (k = 0.635 and 0.753 respectively), and the intraobserver reproducibility was very good for JZ visualization and continuity (k = 0.884 and 0.816 respectively). Trilaminar endometrial pattern was associated with optimal JZ visualization (p = 0.012). The increase of 1 unit in the level of serum estradiol represents a 9.9% decrease in the odds of unsatisfactory visualization of the JZ (odds ratio [OR] = 0.9; 95% confidence interval [95%CI] = 0.814-0.996; p = 0.042). Endometriosis increases the odds of unsatisfactory visualization by 24 times (OR = 23.7; 95%CI = 1.262-437.057; p = 0.034). The prevalence of discontinuous JZs was of 60%. Myomas and endometriosis were associated with discontinuous JZs (p = 0.034 and 0.016 respectively). Conclusion The assessment of JZ visualization and continuity by 3D ultrasound is reproducible enough to be used in the clinical practice.

Resumo Objetivo Analisar a reprodutibilidade inter e intraobservador da visualização e continuidade da zona juncional (ZJ) por ecografia tridimensional (3D) em mulheres inférteis, e avaliar os fatores sociodemográficos, hormonais e estruturais que afetam essas avaliações. Métodos Um estudo prospectivo conduzido no Centro de Procriação Medicamente Assistida do Hospital Senhora da Oliveira, em Guimarães, Portugal. Foi realizada ecografia transvaginal 3D e gerados 2 volumes por caso. Dois observadores, cegos às avaliações um do outro, analisaram os volumes obtidos e escolheram o melhor corte coronal. Após quatro meses, a mesma análise foi realizada por um dos observadores. A visualização da ZJ foi classificada como ótima, satisfatória e não satisfatória, e a continuidade, como contínua ou descontínua. Foram avaliadas as reprodutibilidades inter e intraobservador. A influência de fatores sociodemográficos, hormonais e estruturais na ZJ foi analisada. Resultados No total, 65 mulheres foram incluídas no presente estudo. A reprodutibilidade interobservador foi substancial para a visualização e continuidade da ZJ (k = 0,635 e 0,753, respetivamente). A reprodutibilidade intraobservador foi muito boa para a visualização e continuidade da ZJ (k = 0,884 e 0,816, respetivamente). Endométrio trilaminar associou-se à visualização ótima da ZJ (p = 0.012). O aumento de 1 unidade no nível de estradiol diminuiu a chance de visualização não satisfatória da ZJ em 9,9% (razão de probabilidades [RP] = 0,9; intervalo de confiança de 95% [CI95%] = 0,814-0,996; p = 0,042). Endometriose aumentou a chance de visualização não satisfatória da ZJ em 24 vezes (RP = 23,7; CI95% = 1,262-437,057; p = 0,034). A prevalência de ZJs descontínuas foi de 60%. Miomas e endometriose associaram-se a ZJs descontínuas (p = 0,034 e 0,016, respetivamente). Conclusão A avaliação da visualização e continuidade da ZJ por ecografia 3D é reprodutível, podendo ser utilizada na prática clínica.

Sintomatologia depressiva no termo da gestação, em mulheres de baixo risco / Depressive symptomatology at full-term pregnancy in low risk women

RESUMO Objetivos Calcular a prevalência de sintomatologia depressiva pré-natal em grávidas de baixo risco, no termo da gestação, avaliar seus preditores e desfechos materno-fetais. Para tal, avaliar-se-á a aplicabilidade da Escala de Rastreio de Depressão Pós-Parto (PDSS 24) nessa fase da gravidez. Métodos A PDSS 24 e um questionário sociodemográfico, psicossocial e médico (antecedentes obstétricos e patológicos) foram autoaplicados a 403 grávidas (37-40 semanas de gestação), com idade média de 30,5 anos (DP = 4,67). Por meio do processo clínico, foram recolhidos dados de resultados materno-fetais. Resultados A PDSS 24 possui propriedades psicométricas adequadas para a deteção de sintomatologia depressiva pré-natal. A prevalência de sintomatologia depressiva pré-natal foi de 41,7%. Grávidas com níveis de escolaridade inferiores, não casadas, cuja gravidez não foi planejada e com antecedentes de acontecimentos de vida significativos apresentam risco duas vezes superior de sintomatologia depressiva no período pré-natal. Grávidas cujo apoio social percebido ao longo da gravidez não correspondeu ao desejado e com história prévia de depressão apresentam cerca de três vezes maior risco sintomatologia depressiva no período pré-natal. Para desfechos materno-fetais (pré-eclâmpsia, restrição de crescimento fetal, Apgar 1º/5º minuto, tipo de parto, percentil de peso, oligoâminos e necessidade de cuidados intensivos), as diferenças foram não significativas. Conclusão O rastreio da depressão pré-natal deve ser realizado na gravidez. Porém, no termo da gestação o uso da PDSS 24 como ferramenta de deteção de sintomatologia depressiva deve ser feito com cautela. A elevada prevalência de sintomas relacionados com o sono nessa fase da gestação pode conduzir ao sobre diagnóstico, usando a PDSS 24.

ABSTRACT Objectives The aims of the study were to estimate the prevalence of depressive symptomatology in full-term pregnancy (low risk), evaluate their predictors and maternal-fetal outcomes. To this end, the applicability of Postpartum Depression Screening Scale (PDSS 24) will be evaluated, at full-term pregnancy. Methods PDSS 24 and a sociodemographic, psychosocial, pathological and obstetrical background questionnaire were self-administered to 403 pregnant women (37-40 weeks gestation), with a mean age of 30.5 years (SD = 4.67). Data from maternal, fetal and neonatal outcomes were collected from the patient clinical process. Results PDSS 24 revealed adequate psychometric properties to screening depressive symptomatology in full-term pregnancy. The prevalence of depressive symptomatology was 41.7%. Pregnant women with lower study levels, who weren't married, whose pregnancy was unplanned and with a previous history of significant life events present twice the risk to present depressive symptomatology. Pregnant women who hadn't received the desired social support in pregnancy and with a history of depression present about a 3-fold increased risk to present depressive symptomatology. For maternal-fetal outcomes (pre-eclampsia, fetal growth restriction, Apgar score at 1st/5th minute, type of delivery, weight percentile, oligohydramnios and need for neonatal intensive care), the differences were not significant. Conclusion Screening for prenatal depression should be conducted during pregnancy. However, in full-term pregnancy women, the use of PDSS 24 as a screening tool for depressive symptomatology should be done with caution. The high prevalence of sleep-related symptoms, in full-term pregnancy, may lead to overdiagnosis, using PDSS 24.

Development of a birthweight standard and comparison with currently used standards. What is a 10th centile?

INTRODUCTION: Fetal growth charts are often used in clinical practice. It is important to understand the usefulness and the pitfalls associated with these tools. Without validation, it is difficult to ascertain if the cutoffs we intend are the ones we actually select. We developed a national standard for birthweight (BW) and compared it with other published reference values. STUDY DESIGN: Multicenter retrospective study. We collected data on live births, including first trimester ultrasound and pathology, from 23 to 42 weeks' gestational age (GA). We used a variation of the lambda (λ), mu (µ), and sigma (σ) method (LMS) to construct and smooth predicted centiles. GA data was plotted and modeled in days from 24 to 42 weeks. Resulting centiles were validated and compared with other published and widely used reference values. Data from both BW and estimated fetal weight was used to validate the model. RESULTS: Data on 661,338 births were collected from 22 institutions, including 71,515 cases with first trimester ultrasound. We excluded preterm cesarean section from analysis, because of a significant bias (up to 18%) on BW and used exclusively first trimester ultrasound dates from 34 to 42 weeks. The standard compares favorably with tables currently in use, both ultrasound and birthweight based. CONCLUSION: The use of first trimester ultrasound limits variability by minimizing some random error sources, such as data introduction and GA errors, while allowing better precision (GA in days). This results in a narrower range in the extreme centiles than other charts. Validation with estimates of fetal weight are sound in second and early third trimester fetuses, because that will be a "real world" usage of this standard. While there are similarities between our series and some international/foreign growth charts, other are unfit to characterize our population. This reinforces the need for validation of standards, and sound methodological practices when doing so.

Gestational age and fetal growth assessment among obstetricians.

OBJECTIVE: We aimed to characterize gestational age assessment and fetal growth evaluation among obstetricians. METHODS: Observational, cross-sectional study. We applied a questionnaire to obstetrics specialists and residents, during a national congress on obstetrics. RESULTS: Almost all 179 respondents correct gestational age in the first trimester by ultrasound, but 63% only if there is a difference of 2-9 days. Ultrasound at 11-13 weeks was considered more accurate than at 8-10 weeks by 81%, with a higher proportion of specialists choosing correctly the last answer (p = 0.05). One-third of the respondents did not correctly point the error associated with the ultrasound estimation of fetal weight (EFW). Of the 88% who use a growth table, only 32% were able to identify it by publication/author. Ninety-eight percent identify fetal growth restriction risk (FGR) with centiles (10th in 76%) and 73% of doctors diagnose FGR without other pathological findings (10th in 49%). 44% finds that a low EFW centile maintenance (4th to 3rd) is more worrisome than the crossing of two quartiles (75th to 24th). CONCLUSIONS: The role of ultrasound in gestational age assessment and use of EFW use for FGR classification was disparate among participants. EFW and respective centiles may be over relied upon.

Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia.

Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia.

Feasibility and reproducibility of transvaginal, transabdominal, and 3D volume reconstruction sonography for measurement of the corpus callosum at different gestational ages.

OBJECTIVE: To compare the feasibility and reproducibility of transvaginal and transabdominal approaches, and 3D volume reconstruction sonography for measurement of corpus callosum (CC) length at different gestational ages. METHODS: Forty-six normal fetuses were examined by 2D and 3D ultrasound at 23-25, 27-28 and 31-32 weeks of gestation. Direct mid-sagittal views were obtained by either a transabdominal and/or transvaginal approach. 3D reconstructed mid-sagittal views were obtained by 3D multiplanar manipulations and Volume Contrast Imaging in the C-plane technique (VCI-C) from volumes acquired in axial planes. RESULTS: The CC could be measured in 91% of transvaginal acquisitions, in 52% of transabdominal acquisitions, in 92% of multiplanar reconstructions, and in 86% of VCI-C reconstructions. The success rate was independent of gestational age for transvaginal acquisition and slightly dependent on gestational age for 3D reconstruction techniques. Transabdominal acquisition was dependent on gestational age and fetal presentation. Inter- and intra-observer agreement was slightly better for measurements obtained from direct mid-sagittal views with either transvaginal or transabdominal acquisition than in views obtained by volume reconstruction. The reproducibility of measurements taken in reconstructed mid-sagittal views decreased with gestational age. CONCLUSION: 3D volume reconstruction techniques allow visualization and measurement of the CC in a high percentage of cases, with good reproducibility.

[Validity of classical fetal weight charts in the Portuguese population]. / Validade das tabelas de peso fetal clássicas para a população Portuguesa.

PURPOSE: to assess the validity of several fetal weight charts, commonly used in Portugal, to classify its population. METHODS: observational retrospective study. Singleton birth data was analyzed, from a two- year period (May 2008 to April 2010), from pregnancies with an ultrasound in the same institution, between the 8th and 14th gestational week. Upon data validation, percentiles for each completed gestational week were created, smoothed by a quadratic function, analyzed and compared to the tables more commonly utilized, in the institution and country, by using Z-scores, percentile comparison, sample 10th percentile detection sensibility and birthweight means comparison. RESULTS: a total of 5,378 newborns (NB) were born in the period; 2,195 (42%) NB were included, born from the 24th to 42nd gestational week, allowing statistical analysis from the 34th to the 41st week. There were differences in the mean birthweight for each gestational age, between references and with the sample, as well as between sexes. The 10th percentile from some references has shown differences ranging from -288g at 37 weeks (-11% in Lubchenco et al. data), with and +133g at 34 weeks (+7,6% with Carrascosa et al. data) compared to the values found with the sample. Differences were also found concerning the sensitivity of the identification of a sample birthweight below the 10th percentile, which was between 14.1 and 100%, depending on the reference used. DISCUSSION: the limitation of these kinds of reference values must be remembered and minimized, with the adoption of regionally or nationally produced references, contemplating other variables, such as sex, with precisely known gestation duration and with validation of the utilized references in loco.

Validade das tabelas de peso fetal clássicas para a população Portuguesa / Validity of classical fetal weight charts in the Portuguese population

OBJETIVO: avaliar a validade de várias tabelas de peso fetal, habitualmente usadas em Portugal, para classificar a sua população. MÉTODOS: estudo observacional retrospectivo. Foram analisados os registos de nascimentos no período de dois anos (Maio de 2008 a Abril de 2010), decorrentes de gestações unifetais com datação precisa por ecografia entre as 8ª e 14ª semanas de gestação, na mesma instituição. Após validação dos registos, foram analisados os percentis de peso gerados para cada semana de gestação completa, suavizados por uma função polinomial de dois graus, comparando-os com as tabelas mais usadas na instituição e no país, através do uso de Z-scores, valores de percentis, sensibilidade para detecção do percentil 10 (P10) da amostra e comparação de médias de peso. RESULTADOS: um total de 5.378 recém-nascidos (RN) foi registado no período; 2.195 (42 por cento) RN corresponderam aos critérios de inclusão, com idade gestacional (IG) entre as 24ª e 42ª semanas, permitindo uma análise estatística entre as 34ª e as 41ª semanas. Foram detectadas diferenças no peso médio por IG entre tabelas e em relação à amostra, bem como diferenças entre os sexos. O P10 de outros trabalhos mostrou diferenças entre -288g na 37ªs (-11 por cento nos dados de Lubchenco et al.) e +133g na 34ªs (+7,6 por cento nos dados de Carrascosa et al.) em relação ao obtido na amostra. A sensibilidade para detecção de um RN abaixo do P10 na amostra variou, às 39ªs, entre 14,1e 100 por cento, dependendo da tabela usada. DISCUSSÃO: as limitações deste tipo de valores de referência devem ser tidas em consideração, tentando minimizá-las, nomeadamente pela criação de valores locais/regionais ou nacionais, com a contemplação de outras variáveis, sobretudo o sexo do RN, em gravidezes rigorosamente datadas e pela validação in loco dos valores utilizados.

PURPOSE: to assess the validity of several fetal weight charts, commonly used in Portugal, to classify its population. METHODS: observational retrospective study. Singleton birth data was analyzed, from a two- year period (May 2008 to April 2010), from pregnancies with an ultrasound in the same institution, between the 8th and 14th gestational week. Upon data validation, percentiles for each completed gestational week were created, smoothed by a quadratic function, analyzed and compared to the tables more commonly utilized, in the institution and country, by using Z-scores, percentile comparison, sample 10th percentile detection sensibility and birthweight means comparison. RESULTS: a total of 5,378 newborns (NB) were born in the period; 2,195 (42 percent) NB were included, born from the 24th to 42nd gestational week, allowing statistical analysis from the 34th to the 41st week. There were differences in the mean birthweight for each gestational age, between references and with the sample, as well as between sexes. The 10th percentile from some references has shown differences ranging from -288g at 37 weeks (-11 percent in Lubchenco et al. data), with and +133g at 34 weeks (+7,6 percent with Carrascosa et al. data) compared to the values found with the sample. Differences were also found concerning the sensitivity of the identification of a sample birthweight below the 10th percentile, which was between 14.1 and 100 percent, depending on the reference used. DISCUSSION: the limitation of these kinds of reference values must be remembered and minimized, with the adoption of regionally or nationally produced references, contemplating other variables, such as sex, with precisely known gestation duration and with validation of the utilized references in loco.

Postpartum spontaneous rupture of a liver hematoma associated with preeclampsia and HELLP syndrome.

We report the case of a 28-year-old nulliparous woman who presented at 36 weeks' gestation with preeclampsia: high blood pressure, proteinuria and edema. Serum test results were normal and platelet count was 155 x 10(3)/mm(3). After 30 h the patient initiated severe epigastric pain and vomits, and lab tests presented a slight increase in liver enzymes. The platelet count remained above 150,000/microL. Cesarean section (CS) was performed. Six hours after CS, she developed a hypovolemic shock and lab tests became increasingly abnormal (liver enzymes increased sharply and hemoglobin and platelet count decreased sharply). Abdominal ultrasound showed suggestive signs of hepatic rupture. The patient was stabilized and exploratory laparotomy was performed. Perihepatic packing was applied. The patient was discharged after 25 days of admission (15 days at the ICU) and three explorative laparotomies. This case highlights the unpredictability of this event based on the changes of liver enzyme values, LDH and platelet count. These changes only occurred when the rupture had already occurred and the patient was in hypovolemic shock.