A new model based on artificial intelligence to screening preterm birth.

OBJECTIVE: The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI). METHODS: This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM. RESULTS: The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001). CONCLUSION: AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.

Cervical pessary plus vaginal progesterone in a singleton pregnancy with a short cervix: an experience-based analysis of cervical pessary's efficacy.

BACKGROUND: Several studies were published about cervical pessary, with controversial results. These studies demonstrated that the patient follow-up after pessary insertion is very different between the study centers and the number of pessary insertions per center was often <30 cases. This study aims to determine cervical pessary performance in singleton pregnancies with a short cervix based on a single center learning curve. METHODS: Between 2011 and 2018, 128 singleton pregnancies between 18 and 24 gestational weeks with a short cervix (<25 mm) were referred to our clinic. All cases were treated with progesterone, and when available in our supplies (due to low resources) cervical pessary was also offered. Three groups were created for statistical analysis: Group 1 (n = 33), treated with progesterone-only; Groups 2 and 3, treated with cervical pessary plus progesterone. Group 2 included the first cases (n = 30) of pessary, defined by a learning curve and cumulative sum analysis, while Group 3 included the subsequent 65 cases. The primary outcome was preterm birth (PTB) < 34 gestational weeks. RESULTS: The learning curve was performed with all cases of pessary plus progesterone, and 30 patients were obtained as the number needed for learning, in our study with two operators. The PTB rate < 34 weeks was 27.3, 20, and 4.6% in groups 1, 2, and 3, respectively. There was no significant difference between Group 1 and 2 (OR 1.1; 95% CI 0.066 - 18.45; p = .945). When comparing Groups 1 and 3 there was a significant difference in PTB rates (OR 0.08; CI95% 0.01-0.42; p = .003). Considering Kaplan-Meyer Survival analysis, we can observe that the performance of progesterone alone (Group 1) was similar to Group 2 (progesterone + first 30 cases of pessary) (p = .432), but the performance of Group 3 (progesterone + subsequent 65 cases of pessary) and Group 1 shows a statistically significant difference (p = .011). CONCLUSION: Learning curve and cumulative sum analysis determined that the application and surveillance of at least 30 patients is required to see significant improvements in the primary outcome of PTB < 34 weeks.

Cervical Pessary Plus Progesterone for Twin Pregnancy with Short Cervix Compared to Unselected and Non-Treated Twin Pregnancy: A Historical Equivalence Cohort Study (EPM Twin Pessary Study).

OBJECTIVE: The present study aims to determine if the use of cervical pessary plus progesterone in short-cervix (≤ 25 mm) dichorionic-diamniotic (DC-DA) twin pregnancies is equivalent to the rate of preterm births (PBs) with no intervention in unselected DC-DA twin pregnancies. METHODS: A historical cohort study was performed between 2010 and 2018, including a total of 57 pregnant women with DC-DA twin pregnancies. The women admitted from 2010 to 2012 (n = 32) received no treatment, and were not selected by cervical length (Non-Treated group, NTG), whereas those admitted from 2013 to 2018 (n = 25), were routinely submitted to cervical pessary plus progesterone after the diagnosis of short cervix from the 18th to the 27th weeks of gestation (Pessary-Progesterone group, PPG). The primary outcome analyzed was the rate of PBs before 34 weeks. RESULTS: There were no statistical differences between the NTG and the PPG regarding PB < 34 weeks (18.8% versus 40.0% respectively; p = 0.07) and the mean birthweight of the smallest twin (2,037 ± 425 g versus 2,195 ± 665 g; p = 0.327). The Kaplan-Meyer Survival analysis was performed, and there were no differences between the groups before 31.5 weeks. Logistic regression showed that a previous PB (< 37 weeks) presented an odds ratio (OR) of 15.951 (95% confidence interval [95%CI]: 1.294-196.557; p = 0.031*) for PB < 34 weeks in the PPG. CONCLUSION: In DC-DA twin pregnancies with a short cervix, (which means a higher risk of PB), the treatment with cervical pessary plus progesterone could be considered equivalent in several aspects related to PB in the NTG, despite the big difference between these groups.

OBJETIVO: Este estudo tem como objetivo determinar se o uso de pessário cervical associado a progesterona em gestações de gêmeos dicoriônicos-diamnióticos (DC-DAs) com colo do útero curto (≤ 25 mm) apresenta taxa de parto prematuro (PP) equivalente à de gestações gemelares DC-DA sem nenhuma intervenção/não selecionadas. MéTODOS: Um estudo de coorte histórica foi realizado entre 2010 e 2018, incluindo um total de 57 mulheres grávidas com gestações gemelares DC-DA. As mulheres admitidas de 2010 a 2012 (n = 32) não receberam tratamento, e não foram selecionadas pelo comprimento cervical (grupo Não Tratado, GNT), enquanto as admitidas de 2013 a 2018 (n = 25) receberam pessário cervical rotineiramente associado a progesterona após o diagnóstico de colo curto entre a 18a e a 27ª semanas de gestação (grupo Pessário-Progesterona, GPP). O desfecho primário analisado foi a taxa de PP antes de 34 semanas. RESULTADOS: Não houve diferenças estatísticas entre o GNT e o GPP em relação ao PP < 34 semanas (respectivamente, 18,8% versus 40,0%; p = 0,07) e ao peso médio ao nascer do gêmeo menor (2.037 ± 425 g versus 2.195 ± 665 g; p = 0,327). A análise de Kaplan-Meyer foi realizada, e não houve diferenças entre os grupos antes de 31,5 semanas. A regressão logística demonstrou que o nascimento prematuro anterior (< 37 semanas) apresentou razão de probabilidades (odds ratio, OR) de 15,951 (intervalo de confiança de 95% [IC95%]: 1,294­196,557; p = 0,031*) para o nascimento prematuro < 34 semanas no GPP. CONCLUSãO: Em gêmeos DC-DA com colo uterino curto (o que significa maior risco de nascimento prematuro), o tratamento com pessário cervical associado a progesterona pode ser considerado equivalente em diversos aspectos relacionados à prematuridade no GNT, apesar da grande diferença entre os grupos.

Surgical treatment of tubal ectopic pregnancy through posterior colpotomy: experience from a Brazilian university hospital.

The objective of this study was to evaluate the feasibility of posterior colpotomy for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women. We performed a retrospective analysis of medical records obtained over a period of 18 months. Twelve cases were identified, with the following characteristics: mean gestational age, 7.7 weeks; mean serum ß-human chorionic gonadotropin level, 7,786 mIU/mL; and greater diameter of the mass, 15-69 mm. Treatment was successful in all cases. Salpingectomy was performed in 10 patients (83.3%) and salpingostomy, in 1 patient. The remaining patient only received peritoneal lavage, as the evidence of ectopic abortion with only a slightly dilated uterine tube was found during surgery. The mean surgical time was 42.5 minutes. In the analyzed cases, posterior colpotomy was found to be a feasible alternative method for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women.

Fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome treatment: initial experience in tertiary reference center in Brazil.

OBJECTIVE: To evaluate the initial maternal and perinatal outcomes of fetoscopic laser photocoagulation for the treatment of twin-to-twin transfusion syndrome (TTTS) in a referral center in Brazil. METHODS: This prospective observational study analyzed 24 fetoscopic laser photocoagulation procedures at 18-26 weeks of gestation. TTTS severity was determined using the Quintero classification. Blood vessels that crossed the interamniotic membrane were nonselectively photocoagulated. The χ2 test and Mann-Whitney U test were used for the statistical analysis. RESULTS: The mean (±standard deviation) age of pregnant women, gestational age at surgery, surgical time, gestational age at birth, and newborn weight were 32.2±4.1 years, 20.7±2.9 weeks, 51.8±16.7 minutes, 30.5±4.1 weeks, and 1,531.0±773.1 g, respectively. Using the Quintero classification, there was a higher percentage of cases in stage III (54.2%), followed by stages IV (20.8%), II (16.7%), and I (8.3%). Ten (41.7%) donor fetuses died and 14 (58.3%) donor fetuses survived until the end of gestation. Placental insertion location (anterior vs. posterior) did not affect the incidence of iatrogenic septostomy, surface bleeding, and premature rupture of membranes until the end of gestation. The death rate of donor and recipient fetuses before 24th gestational week increased with severity of TTTS. CONCLUSION: The maternal and perinatal outcomes resulting from the implementation of a new minimally invasive surgical technique are in line with those obtained in major centers worldwide, considering the learning curves and infrastructures.

Local management with methotrexate of cesarean scar ectopic pregnancy with live embryo guided by transvaginal ultrasound: A case report.

Cesarean scar ectopic pregnancy is a rare type of ectopic pregnancy with high morbidity and mortality. Use of conservative conducts, including medical management with methotrexate, has avoided mutilating surgeries such as hysterectomy and spared the fertility of women. We report the case of a 30-year old patient with a cesarean scar ectopic pregnancy, with a live embryo, who was treated locally with transvaginal ultrasound-guided injection of methotrexate, complemented with various doses of systemic methotrexate.

Local management with methotrexate of cesarean scar ectopic pregnancy with live embryo guided by transvaginal ultrasound: A case report / Tratamento local com metotrexato guiado por ultrassonografia transvaginal de gravidez ectópica em cicatriz de cesárea com embrião vivo: relato de caso

Summary Cesarean scar ectopic pregnancy is a rare type of ectopic pregnancy with high morbidity and mortality. Use of conservative conducts, including medical management with methotrexate, has avoided mutilating surgeries such as hysterectomy and spared the fertility of women. We report the case of a 30-year old patient with a cesarean scar ectopic pregnancy, with a live embryo, who was treated locally with transvaginal ultrasound-guided injection of methotrexate, complemented with various doses of systemic methotrexate.

Resumo A gravidez ectópica na cicatriz de cesárea é uma forma rara de gestação ectópica com elevada morbimortalidade. O emprego de condutas conservadoras, como o tratamento medicamentoso com metotrexato, tem evitado cirurgias mutiladoras, como a histerectomia, e preservado o futuro reprodutivo da mulher. Relatamos um caso de paciente de 30 anos, com gravidez ectópica em cicatriz de cesárea, com embrião vivo, tratada com injeção local de metotrexato guiada por ultrassonografia transvaginal, complementada com tratamento sistêmico com múltiplas doses de metotrexato.

Interventional radiology and endovascular surgery in the treatment of ectopic pregnancies.

The advent of interventional radiology enabled remarkable advances in diagnosis and treatment of several situations in obstetrics and gynecology. In the field of obstetrics, these advances include temporary occlusion of the iliac arteries to the management of placenta accreta and/or prior, arteriovenous fistulas after embolization of uterine curettage and management of ectopic uterine and extra-uterine pregnancies. The non-tubal ectopic pregnancy, either cervical, abdominal, ovarian or in a cesarean scar, often represents major therapeutic challenge, especially when exists a desire to maintain fertility. Despite the systemic methotrexate therapy and surgical resection of the ectopic gestational sac be the most used therapeutic options, the interventionist approach of non-tubal ectopic pregnancies, direct injection of methotrexate in the gestational sac and intra-arterial chemoembolization of uterine arteries constitute in the currently literature viable, safe, effective modalities with low morbidity, shorter hospital stay, and rapid clinical recovery. Because of little variety of materials used, and the increase in training of specialists in the area, the radiological intervention as a treatment option in ectopic pregnancies is financially viable and present considerable accessibility in the world and at most of Brazilian medical centers.

Interventional radiology and endovascular surgery in the treatment of ectopic pregnancies / Radiologia intervencionista e cirurgia endovascular no tratamento das prenhezes ectópicas

The advent of interventional radiology enabled remarkable advances in diagnosis and treatment of several situations in obstetrics and gynecology. In the field of obstetrics, these advances include temporary occlusion of the iliac arteries to the management of placenta accreta and/or prior, arteriovenous fistulas after embolization of uterine curettage and management of ectopic uterine and extra-uterine pregnancies. The non-tubal ectopic pregnancy, either cervical, abdominal, ovarian or in a cesarean scar, often represents major therapeutic challenge, especially when exists a desire to maintain fertility. Despite the systemic methotrexate therapy and surgical resection of the ectopic gestational sac be the most used therapeutic options, the interventionist approach of non-tubal ectopic pregnancies, direct injection of methotrexate in the gestational sac and intra-arterial chemoembolization of uterine arteries constitute in the currently literature viable, safe, effective modalities with low morbidity, shorter hospital stay, and rapid clinical recovery. Because of little variety of materials used, and the increase in training of specialists in the area, the radiological intervention as a treatment option in ectopic pregnancies is financially viable and present considerable accessibility in the world and at most of Brazilian medical centers.

O advento da radiologia intervencionista tornou possível avanços notáveis no diagnóstico e no tratamento de diversas situações, na área de ginecologia e obstetrícia. No campo da obstetrícia, esses avanços incluem oclusão temporária das artérias hipogástricas para o manejo de placenta acreta e/ou prévia, embolização de fístulas arteriovenosas após curetagem uterina e manejo de prenhezes ectópicas uterinas e extrauterinas. A gravidez ectópica não tubária, seja cervical, abdominal, ovariana ou na cicatriz de cesárea, muitas vezes representa grande desafio terapêutico, principalmente quando há desejo de manutenção da fertilidade. As opções terapêuticas mais utilizadas para o tratamento de prenhez ectópica não tubária, são: terapia sistêmica com metotrexato e ressecção cirúrgica do saco gestacional ectópico; porém a abordagem intervencionista com injeção direta de metotrexato no saco gestacional ou quimiembolização intra-arterial das artérias uterinas, apresentam-se na literatura recente, como modalidades terapêuticas viáveis, seguras, eficazes, com baixa morbidade, menor tempo de internação e rápida recuperação clínica. Devido ao diminuto arsenal de materiais utilizados e à crescente formação de especialistas na área, a intervenção radiológica, como opção de tratamento nas prenhezes ectópicas, é financeiramente viável e apresenta acessibilidade considerável no mundo e na maioria do centros médicos brasileiros.

Effectiveness of expectant management versus methotrexate in tubal ectopic pregnancy: a double-blind randomized trial.

PURPOSE: To compare the effectiveness of expectant management versus methotrexate in selected cases of tubal ectopic pregnancy. METHODS: A double-blind randomized trial included 23 selected patients with a confirmed diagnosis of tubal pregnancy who met the inclusion criteria (hemodynamic stability, initial serum ß-hCG concentration <2,000 mIU/mL, declining titers of ß-hCG 48 h prior to treatment, visible tubal pregnancy on transvaginal ultrasound, a tubal mass <5.0 cm and fertility desire). The patients were divided into two groups: 10 patients in the methotrexate group (MTX 50 mg/m(2) administered as a single intramuscular dose) and 13 patients in the placebo group (saline solution administered in a single intramuscular dose). Quantitative variables were expressed as means ± standard deviations and compared by Student's t test or Mann-Whitney test. Dichotomous variables (success/treatment failure) were presented as proportions and compared by the Fisher exact test. RESULTS: Successful treatment with negative titers of ß-hCG occurred in 9 cases (90.0%) of the methotrexate group and in 12 (92.3%) of the placebo group (p > 0.999). The ß-hCG values became undetectable at 22 ± 15.4 days in the methotrexate group and 20.6 ± 8.4 days in the placebo group (p = 0.80). CONCLUSION: This study showed no statistically significant difference between the treatment with methotrexate and placebo, with similar success rates and similar time interval for ß-hCG to become undetectable.

Methotrexate for ectopic pregnancy: when and how.

PURPOSE: Ectopic pregnancy is the leading cause of maternal death in the first trimester of pregnancy. The dosage of beta fraction of human chorionic gonadotropin (beta-hCG) and improvement of the transvaginal ultrasound allowed an earlier diagnosis and a conservative management. Currently, the use of systemic methotrexate (MTX) proved to be a great alternative with similar success rates and completely non-invasive. METHODS: We searched for the most relevant articles on the use of MTX in ectopic pregnancy published between 2003 and 2013 in high-impact journals. We performed a strategic search at the Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), National Institute for Health Research (NHS), International Prospective Register of Systematic Reviews (PROSPERO), The Cochrane Database of Systematic Reviews (CDSR) and Medical Literature Analysis and Retrieval System Online (MEDLINE) according to the descriptors "pregnancy, ectopic" and "methotrexate", alone or combined. RESULTS: Thus, we based this review on 32 studies that were classified following the grades of recommendation and levels of evidence proposed by the Oxford Centre for Evidence-Based Medicine. Additionally, selected papers were used. Scientific evidence points to a growing trend in the choice of conservative treatment for ectopic pregnancies, whereas expectant management still lacks studies for definitive conclusions. Indeed, the well-established protocols which exhibit a greater number of studies are still based on the single-dose treatment. CONCLUSION: Considering MTX, it proved to be more effective in cases of low titers of beta-hCG and masses with a small diameter, although there is still no uniformity of these parameters. The choice largely depends on the experience of the medical team and ultimately, on the woman's reproductive desire.

Complicações fetais na gemelaridade monocoriônica: quadro clínico, fisiopatologia, diagnóstico e conduta / Fetal complications in monochorionic twin pregnancy: clinical features, pathophysiology, diagnosis and management

A incidência de gemelaridade monocoriônica é de um para cada duzentos e cinquenta gestações. A placenta monocoriônica está relacionada a maior risco de complicações gestacionais, como transfusão feto-fetal, restrição seletiva do crescimento fetal, óbito fetal e gêmeo acárdico. Portanto, a avaliação criteriosa da corionicidade, o monitoramento da gestação e a detecção precoce de complicações são fatores importantes para melhorar o desfecho neonatal. Assim, o objetivo deste estudo é descrever as principais complicações fetais da gestação monocoriônica e qual deve ser a conduta obstétrica diante das diversas situações adversas. Foi realizada uma revisão de literatura dos últimos 28 anos, nas bases de dados MEDLINE/Pubmed, Scielo, LILACS e BIREME, sendo encontrados 401 artigos. Dentre estes, 28 estudos foram selecionados para esta revisão.(AU)

The incidence of monochorionic twin pregnancy is one in every two hundred and fifty pregnancies. The monochorionic placenta is associated with higher risk of pregnancy complications, such as fetal-fetal transfusion, selective fetal growth restriction, fetal death and acardiac twin. Therefore, a careful assessment of chorionicity, monitoring of pregnancy and early detection of complications are important factors to improve neonatal outcomes. Thus, the aim of this study is to describe the major fetal complications of monochorionic pregnancy and the better and what should be the obstetric approach considering the various adverse situations. A literature review of the past 28 years was performed in MEDLINE/PubMed, SciELO, LILACS and BIREME, being found 401 articles. Of these, 28 studies were selected for this review.(AU)

Parturient perineal distensibility tolerance assessed by EPI-NO: an observational study / Tolerância da parturiente à extensibilidade perineal avaliada pelo EPI-NO: estudo observacional / Tolerância da parturiente à extensibilidade perineal avaliada pelo EPI-NO: estudo observacional

Objective : To determine how parturient women tolerate the use of a perineal distensibility assessment technique using the EPI-NO device. Methods : An observational study with a total of 227 full-term parturient women was performed. During the evaluation with EPI-NO, parturient patients were asked about their sensation of discomfort. The degree of discomfort was measured using the Visual Analogue Scale, with a score from zero to 10. The Mann-Whitney test was applied to assess perineal distensibility measured by EPI-NO and the degree of discomfort caused by the test according to parity. The relation between perineal distensibility and discomfort was analyzed by using the Spearman correlation test (r). Results : The test with EPI-NO caused only slight discomfort (mean Visual Analogue Scale of 3.8), and primiparous women reported significantly greater discomfort (mean Visual Analogue Scale of 4.5) than did multiparous (mean Visual Analogue Scale=3.1), with p<0.001 women. A negative correlation was observed, in other words, the greater the perineal distensibility on the EPI-NO, the lower the pain reported by the patients (r=-0.424; p<0.001). Conclusion : The assessment of perineal distensibility with EPI-NO was well tolerated by the parturient women. .

Objetivo : Determinar como a mulher parturiente tolera o uso de uma nova técnica de extensibilidade perineal, por meio do aparelho EPI-NO. Métodos : Estudo observacional com um total de 227 gestantes a termo. Durante a avaliação pelo EPI-NO, as parturientes foram perguntadas sobre a sensação de desconforto. O grau de desconforto foi medido usando a Escala Visual Analógica, com escore entre zero a 10. O teste de Mann-Whitney foi usado para avaliar a extensibilidade perineal avaliada pelo EPI-NO e o grau de desconforto causado pelo teste de acordo com a paridade. A relação entre extensibilidade perineal e desconforto foi avaliada pelo teste de correlação de Spearman (r). Resultados : O teste com EPI-NO causou apenas leve desconforto (média da Escala Visual Analógica de 3,8), sendo que as primíparas reportaram mais desconforto de modo significativo (média da Escala Visual Analógica de 4,5) que as multíparas (média da Escala Visual Analógica de 3,1), com p<0,001. Observou-se correlação negativa, ou seja, a maior extensibilidade no EPI-NO foi acompanhada de menor dor referida pelas pacientes (r=-0,424; p<0,001). Conclusão : A avaliação da extensibilidade perineal com EPI-NO foi bem tolerada pelas parturientes. .

Trophoblastic infiltration in tubal pregnancy evaluated by immunohistochemistry and correlation with variation of Beta-human chorionic gonadotropin.

Objective. To evaluate trophoblastic cell proliferation and angiogenesis in tubal pregnancy assessed by immunohistochemical study and their correlation with an average variation of ß -hCG in an interval of 48 hours before surgery. Methods. A prospective study was conducted on 18 patients with a diagnosis of tubal pregnancy. The patients were divided into two groups of ectopic pregnancy of which 11 showed rise of ß -hCG levels and 7 patients showed declining ß -hCG levels in an interval of 48 hours prior to surgery. Trophoblastic cell proliferation and angiogenesis were assessed by Ki-67 and VEGF, respectively. Trophoblastic cell proliferation was assessed by Ki-67 and was classified into three groups (grade I: less than 1/3 of stained nuclei, grade II: 1/3 to 2/3 of the stained nuclei, and grade III: more than 2/3 of the nuclei stained). The cases analyzed for VEGF were divided into three groups (grade I: less than 1/3 of the stained cytoplasm; grade II: 1/3 to 2/3 of the stained cytoplasm; grade III: more than 2/3 of the stained cytoplasm). Statistical analysis was performed using the chi-square, ANOVA, and Kruskal-Wallis tests. Results. The mean variation in the serum ß -hCG levels in 48 hours in tubal pregnancy patients correlated with trophoblastic cell proliferation assessed by Ki-67 and showed a decline of 13.46% in grade I, a rise of 45.99% in grade II, and ascension of 36.68% in grade III (P = 0.030). The average variation in the serum ß -hCG in 48 hours, where angiogenesis was evaluated by VEGF, showed a decline of 18.35% in grade I, a rise of 32.95% in grade II, and ascension of 37.55% in grade III (P = 0.047). Conclusions. Our observations showed a direct correlation of increased levels of serum ß -hCG in 48h period prior to surgery with higher trophoblastic cell proliferation assessed by Ki-67 and angiogenesis assessed by VEGF in tubal pregnancy.

Gravidez ectópica cervical com embrião vivo: o uso do metotrexato é eficiente? / Cervical ectopic pregnancy with alive embryo: the use of methotrexate is effective?

A gravidez ectópica cervical é tida como de localização excepcional, representando menos de 1% das implantações ectópicas. Embora rara, constitui patologia obstétrica de elevada gravidade. Sua letalidade, no passado, atingia índices assustadores. Estabelecido o diagnóstico, a conduta clássica era a histerectomia total, pois o sangramento intravaginal oriundo do canal cervical era frequentemente mortal, diante de tentativas de tratamento conservador por curetagem e/ou sutura local, sobretudo em nulíparas, desejosas de manter a fertilidade. Mais recentemente, tem sido proposto o uso do metotrexato por via local e/ou sistêmica, por vezes associado a técnicas de ligadura e embolização arterial, como forma de evitar a cirurgia mutiladora. Este trabalho teve como objetivo buscar evidências científicas na literatura que possam avaliar a eficácia do tratamento dessas pacientes utilizando o metotrexato.

The cervical ectopic pregnancy is considered of exceptional location, less than 1% of ectopic implantations. Although rare, is extremely serious obstetric pathology. Lethality in the past, reached frightening levels. After the diagnosis, the procedure was the classic radical hysterectomy, because the bleeding originated from intravaginal cervical canal was often fatal before the attempts of conservative treatment by curettage and/or suture, especially in nulliparous women desiring to maintain fertility. More recently, it has been suggested the use of methotrexate by local and/or systemic way, frequently associated with techniques of ligation and arterial embolization, in order to avoid mutilating surgery. This study aimed to look for evidence in the scientific literature to evaluate the effectiveness of treatment of these patients using methotrexate.

Gravidez ectópica não rota: diagnóstico e tratamento. Situação atual / Unruptured ectopic pregnancy: diagnosis and treatment. State of art

O diagnóstico não invasivo da gravidez ectópica deve ser realizado precocemente, antes de ocorrer a ruptura tubária, combinando a ultra-sonografia transvaginal com a dosagem da fração beta do hormônio gonadotrófico coriônico. Diversas opções de tratamento podem ser utilizadas. Devemos respeitar as indicações tanto das intervenções cirúrgicas como do tratamento clínico. A laparotomia está indicada nos casos de instabilidade hemodinâmica. A laparoscopia é a via preferencial para o tratamento da gravidez tubária. A salpingectomia deve ser realizada nas pacientes com prole constituída. A salpingostomia é indicada nas pacientes com desejo reprodutivo, quando os títulos da b-hCG forem inferiores a 5000 mUI/mL e as condições cirúrgicas forem favoráveis. O tratamento com metotrexato (MTX) é uma conduta consagrada, podendo ser indicado como primeira opção de tratamento. Os principais critérios para indicação do MTX são estabilidade hemodinâmica, b-hCG <5.000 mUI/mL, massa anexial <3,5 cm e ausência de embrião vivo. A dose única 50 mg/m² intramuscular é a preferencial por ser mais fácil, mais prática e com menores efeitos colaterais. O protocolo com múltiplas doses deve ficar restrito para os casos de localização atípica (intersticial, cervical, cicatriz de cesárea e ovariana) com valores de b-hCG >5.000 mUI/mL e ausência de embrião vivo. A indicação do tratamento local com injeção de MTX (1 mg/kg) guiada por ultra-sonografia transvaginal é na presença de embrião vivo nos casos de localização atípica. A conduta expectante deve ser indicada nos casos de declínio dos títulos da b-hCG em 48 horas antes do tratamento e quando os títulos iniciais são inferiores a 1.500 mUI/mL. Em relação ao futuro reprodutivo, existem controvérsias entre a salpingectomia e a salpingostomia. Até obtermos um consenso na literatura, orientamos às pacientes desejosas de uma futura gestação a optar pelas condutas conservadoras, tanto cirúrgicas como clínicas.

It is advisable to do the non-invasive diagnosis of ectopic pregnancy precociously, before there is the tube rupture, combining for that the transvaginal ultrasonography with the dosage of the b-fraction of the chorionic gonadotrophin. A range of treatment options may be used. Either a surgical intervention or a clinical treatment may be taken into consideration. Laparotomy is indicated in cases of hemodynamic instability. Laparoscopy is the preferential route for the treatment of tube pregnancy. Salpingectomy should be performed in patients having the desired number of children, while salpingostomy should be indicated in patients willing to have more children, when the b-hCG titers are under 5,000 mUI/mL and the surgical conditions are favorable. The use of methotrexate (MTX) is a consecrated clinical procedure and should be indicated as the first option of treatment. The main criteria for MTX indication are hemodynamic stability, b-hCG <5,000 mUI/mL, anexial mass <3,5 cm, and no alive embryo. It is preferable a single intramuscular dose of 50 mg/m², because it is easier, more practical and with less side effects. Protocol with multiple doses should be restricted for the cases with atypical localization (interstitial, cervical, caesarean section scar and ovarian) with values of b-hCG >5,000 mUI/mL and no alive embryo. Indication for local treatment with an injection of MTX (1 mg/kg) guided by transvaginal ultrasonography should occur in cases of alive embryos, but with an atypical localization. An expectant conduct should be indicated in cases of decrease in the b-hCG titers within 48 hous before the treatment, and when the initial titers are under 1,500 mUI/mL. There are controversies between salpingectomy and salpingostomy, concerning the reproductive future. Till we reach an agreement in the literature, the advice to patients who are looking forward to a future gestation, is to choose either surgical or clinical conservative conducts.

Unruptured tubal pregnancy: different treatments for early and late diagnosis

CONTEXT AND OBJECTIVE: There is evidence that ectopic pregnancies present different behavioral patterns. These distinct evolutions of ectopic pregnancies represent two different natural histories. To evaluate these evolution patterns, we compared patients undergoing medical treatment and expectant management according to their gestational age and initial beta-hCG levels. DESIGN AND SETTING: Prospective study at the Department of Obstetrics of Universidade Federal de São Paulo, a tertiary center. METHODS: Among 119 cases of unruptured ectopic pregnancies diagnosed from April 1999 to February 2004, 57 received systemic treatment with methotrexate 50 mg/m² (body surface area) intramuscularly and 62 were managed expectantly. In this study we evaluated the beta-hCG levels at presentation and amenorrhea duration. RESULTS: There was a significant difference between the two groups regarding amenorrhea duration and initial beta-hCG levels (p < 0.001). The group with decreasing beta-hCG levels (managed expectantly) had longer amenorrhea (mean: 8.87 ± 1.71 weeks) and lower initial beta-hCG levels (mean: 648.8 ± 754.7 mIU/ml). On the other hand, the group treated with methotrexate had shorter amenorrhea (mean: 6.81 ± 1.88 weeks) and higher beta-hCG levels at presentation (2642.7 ± 2315.1 mIU/ml). CONCLUSIONS: The data suggest that ectopic pregnancies can be categorized into two groups: those with early diagnosis and shorter amenorrhea, increasing or maintained beta-hCG levels over 24 and 48-hour intervals and higher beta-hCG levels requiring medical treatment; and those with late diagnosis and longer amenorrhea, decreased beta-hCG levels over 24 and 48-hour intervals and lower beta-hCG levels requiring expectant management.

CONTEXTO E OBJETIVO: A gravidez ectópica apresenta comportamentos diferentes. Para avaliar as diferentes evoluções da gravidez ectópica, nós comparamos as pacientes submetidas ao tratamento medicamentoso e à conduta expectante de acordo com a idade gestacional e os valores iniciais de beta-hCG. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado no Departamento de Obstetrícia da Universidade Federal de São Paulo, hospital terciário. MÉTODOS: Foram diagnosticados 119 casos de gravidez ectópica íntegra no período de abril de 1999 a fevereiro de 2004. O tratamento com metotrexato 50 mg/m² de superfície corpórea intramuscular foi realizado em 57 casos e a conduta expectante, em 62 casos. Neste estudo, nós avaliamos os valores iniciais de beta-hCG e o período de amenorréia. RESULTADOS: Houve diferença estatística significante entre os dois grupos com relação ao período de amenorréia e os valores iniciais de beta-hCG (p < 0,001). O grupo com títulos de beta-hCG em regressão (conduta expectante) apresentaram período de amenorréia mais longo (média:8,87 ± 1,71 semanas) e valores iniciais de beta-hCG mais baixos (648,8 + 754,7 mUI/ml). Por outro lado, o grupo tratado com metotrexato teve período menor de amenorréia (média 6,81 + 1,88 semanas) e valores de beta-hCG mais altos (2642,7 +2315,1 mUI/ml). CONCLUSÕES: Os resultados deste estudo sugerem que a gravidez ectópica pode ser categorizada em dois grupos: aquelas com diagnóstico precoce com período curto de amenorréia e valores elevados de beta-hCG que requerem tratamento com metotrexato, e aquelas com diagnóstico tardio com período longo de amenorréia e valores baixos de beta-hCG que requerem a conduta expectante.