Caracterización de enfermedad trofoblástica gestacional en el Hospital de Talca, 2013-2022 / Characterization of gestational trophoblastic disease at Hospital de Talca, 2013-2022

Introducción: La enfermedad trofoblástica gestacional (ETG) corresponde al espectro de lesiones proliferativas del tejido trofoblástico placentario. Presenta una incidencia mundial variable; en Chile no existen estudios nacionales, por lo que las cifras se deben extrapolar de estudios extranjeros. Objetivo: Caracterizar clínica y epidemiológicamente a las pacientes diagnosticadas con embarazo molar en el periodo 2013-2022 en el Hospital Regional de Talca (HRT). Método: Estudio observacional transversal, se consideró el recuento total de pacientes de la base de datos del Servicio de Onco-Ginecología (n = 100) y la cantidad de embarazos ocurridos entre 2013-2022 en el HRT. Resultados: La edad promedio de presentación fue de 32 años, obteniéndose una incidencia de ETG de 2,1 casos por cada 1.000 embarazos. El 54% de los casos corresponde a mola parcial. Los principales síntomas fueron metrorragia (67%) y dolor abdominal (40%). El principal tratamiento efectuado fue aspiración uterina (92%). En el 48% de los casos se sospechó la ETG con la clínica previo al diagnóstico por biopsia y solo en un 13% únicamente con estudio ecográfico. Conclusiones: Es necesario realizar más investigaciones nacionales que permitan recopilar información actualizada sobre ETG, sobre todo por la variabilidad clínica de la enfermedad, que hace difícil su sospecha diagnóstica.

Introduction: Gestational trophoblastic disease (GTO) corresponds to the spectrum of proliferative lesions of placental trophoblastic tissue. It has a variable global incidence; in Chile there are no national studies so it must be extrapolated from foreign studies. Objective: To clinically and epidemiologically characterize patients diagnosed with molar pregnancy in the period 2013-2022, at the Talca Regional Hospital (HRT). Method: Cross-sectional observational study, the total count of patients from the Onco-Gynecology Service database (n = 100) and the number of pregnancies that occurred between 2013-2022 in the HRT were considered. Results: The average age of presentation was 32 years, obtaining an incidence of GTO of 2.1 cases per 1000 pregnancies; 54% of cases correspond to partial mole. The main symptoms were metrorrhagia (67%) and abdominal pain (40%). The main treatment performed was uterine aspiration (92%). In 48% of the cases, GTO was suspected with clinical symptoms prior to diagnosis by biopsy, and only 13% with an ultrasound study alone. Conclusions: It is necessary to carry out more national research to collect updated information on GTO, especially due to the clinical variability of the disease that makes its diagnostic suspicion difficult.

Partial hydatidiform mole and coexisting fetus after frozen embryo transplantation: a case report.

Hydatidiform mole and coexisting fetus is a very rare condition of which etiology is still inconclusive. It may occur after assisted reproduction, often leading to the death of normal embryos and other serious complications. We report a case of partial hydatidiform mole and coexisting fetus after frozen embryo transplantation. More than two months after the patient underwent transplantation with two blastocysts (scored 4AB and 4BC), B-ultrasound showed a single live fetus with a large dense dotted strong echo area. The patient was treated with chemotherapy after the termination of pregnancy due to persistently increased human chorionic gonadotropin levels. Many studies have described trophoblast quality as a strong predictor of pregnancy. In the case in question, in addition to partial hydatidiform mole caused by multiple sperm entering the egg, we also speculate that the condition may be related to the poor quality of the trophoblastic ectoderm of the transferred embryo. In the process of assisted reproduction, the transfer of embryos with poor trophoblastic ectoderm in multiple embryo transfers may adversely affect pregnancy outcomes.

Presentation, medical complications and development of gestational trophoblastic neoplasia of hydatidiform mole after intracytoplasmic sperm injection as compared to hydatidiform mole after spontaneous conception - a retrospective cohort study and literature review.

OBJECTIVE: To describe the natural history of hydatidiform mole (HM) after intracytoplasmic sperm injection (ICSI), emphasizing the clinical and oncological outcomes, as compared to patients who had HM after spontaneous conception (SC). STUDY DESIGN: Retrospective historical cohort study of patients with HM followed at the Rio de Janeiro Federal University, from January 1st 2000-December 31st 2020. RESULTS: Comparing singleton HM after SC to those following ICSI there were differences in terms of maternal age (24 vs 34 years, p < 0.01), gestational age at diagnosis (10 vs 7 weeks, p < 0.01), preevacuation human chorionic gonadotropin levels (200,000 vs 99,000 IU/L, p < 0.01), occurrence of genital bleeding (60.5 vs 26.9%, p < 0.01) and hyperemesis (23 vs 3.9%, p = 0.02) at presentation, and time to remission (12 vs 5 weeks, p < 0.01), respectively. There were no differences observed in the cases of twin mole, regardless of the form of fertilization that gave rise to HM, except molar histology with greater occurrence of partial hydatidiform mole (10.7 vs 40.0%, p = 0.01) following ICSI. Univariate logistic regression for occurrence of postmolar GTN after ICSI identified no predictor variable for this outcome. However, after adjusting for maternal age and complete hydatidiform mole histology, multivariable logistic regression showed the risk of GTN with HM after ICSI had an adjusted odds ratio of 0.22 (95%CI:0.05-0.93, p = 0.04), suggesting a possible protective effect when compared to HM after SC. CONCLUSIONS: Singleton HM after ICSI are diagnosed earlier in gestation, present with fewer medical complications, and may be less likely to develop GTN when compared with HM after SC.

Influence of COVID-19 pandemic on molar pregnancy and postmolar gestational trophoblastic neoplasia: An observational study.

OBJECTIVE: To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID-19 pandemic. DESIGN: Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross-sectional analysis, with application of a questionnaire. SETTING: Six Brazilian Reference Centres on gestational trophoblastic disease. POPULATION: 2662 patients with MP/postmolar GTN treated from March-December/2015-2020 were retrospectively evaluated and 528 of these patients answered a questionnaire. METHODS: Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross-sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID-19 pandemic compared with previous years. MAIN OUTCOME MEASURES: The incidence of MP/postmolar GTN. RESULTS: Compared with the last 5 pre-pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID-19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be >10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90-3.29, P < 0.001), have a pre-evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38-2.28, P < 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01-3.43, P = 0.047) when compared with 2015-2019. CONCLUSIONS: Although the incidence of MP/postmolar GTN remained stable during the COVID-19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN.

Diagnóstico y tratamiento quirúrgico de una paciente con una neoplasia trofoblástica gestacional / Diagnosis and surgical treatment of a patient with gestational trophoblastic neoplasia

Resumen ANTECEDENTE: La neoplasia trofoblástica gestacional forma parte del grupo de afecciones derivadas de la proliferación anómala del trofoblasto con capacidad para invasión y metástasis. CASO CLÍNICO: Paciente de 42 años, asintomática, con sospecha ecográfica de mola hidatiforme. El legrado uterino y el estudio anatomopatológico confirmaron el diagnóstico de mola hidatiforme completa. Con la cuantificación consecutiva de tres elevaciones de la β-HCG se diagnosticó: neoplasia trofoblástica gestacional. Se estadificó en estadio I, bajo riesgo y ante el deseo genésico satisfecho la paciente aceptó la histerectomía más salpingectomía bilateral. En el seguimiento posterior la paciente se encontró asintomática, con determinaciones seriadas de b-HCG negativa y ecografías vaginales sin hallazgos. CONCLUSIÓN: La histerectomía con salpingectomía bilateral puede ser el tratamiento definitivo en casos seleccionados de neoplasia trofoblástica. La evidencia disponible es escasa, por lo que es necesario seguir investigando en este campo.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is one of a group of conditions resulting from abnormal trophoblast proliferation with capacity for invasion and metastasis. CLINICAL CASE: 42-year-old asymptomatic patient with ultrasound suspicion of hydatidiform mole. Uterine curettage and anatomopathological study confirmed the diagnosis of complete hydatidiform mole. With the consecutive quantification of three elevations of β-HCG a diagnosis of gestational trophoblastic neoplasia was made. It was staged as stage I, low-risk, and the patient agreed to hysterectomy plus bilateral salpingectomy. At subsequent follow-up the patient was found to be asymptomatic, with negative serial determinations of β-HCG and vaginal ultrasound scans without findings. CONCLUSION: Hysterectomy with bilateral salpingectomy may be the definitive treatment in selected cases of trophoblastic neoplasia. The available evidence is scarce and further research is needed in this field.

Mola hidatiforme completa en mujer premenopáusica. Caso clínico / Complete hydatidiform mole in a perimenopausal woman. Clinical case

Resumen ANTECEDENTES: La mola hidatiforme se divide en completa y parcial. La primera se origina en la fecundación de un óvulo anucleado por dos espermatozoides con carga genética independiente y la manifestación clínica predominante son las hemorragias. El tamaño uterino suele ser mayor al normal, con síntomas subjetivos del embarazo. La importancia de este tipo de tumoración es su carácter premaligno que puede evolucionar hasta convertirse en una neoplasia trofoblástica, de tal manera que en la mola completa se transformará en neoplasia. CASO CLÍNICO: Paciente de 43 años que acudió a consulta debido a la caída de su plano de sustentación 3 días antes, con dolor pélvico en el hipogastrio, tipo cólico de intensidad moderada, sin sangrado transvaginal. Refirió estar embarazada, sin recordar la fecha de la última menstruación; sin control prenatal ni ultrasonido previo. A la exploración física el abdomen se encontró globoso, a expensas de útero hipertrófico de 16 x 12 x 10 cm, concentraciones de HGCß mayores de 150,000 mUI/mL. El ultrasonido endovaginal y pélvico reportaron: útero en anteversoflexión, central, aumentado de tamaño por imagen ecográfica en copos de nieve. Diagnóstico: mola hidatiforme. Se indicó la histerectomía abdominal, con hallazgos de útero aumentado de tamaño a expensas de mola completa y anexos sin alteraciones. CONCLUSIÓN: El diagnóstico de la paciente fue fortuito, advertido en el ultrasonido. La conducta terapéutica establecida para este tipo de casos en pacientes mayores con paridad satisfecha permitió que la evolución fuera satisfactoria y continuar en seguimiento.

Abstract BACKGROUND: Hydatidiform mole is divided into complete and partial. The former originates from fertilization of an anucleate ovum by two spermatozoa with independent genetic load and the predominant clinical manifestation is hemorrhage. The uterine size is usually larger than normal, with subjective symptoms of pregnancy. The importance of this type of tumor is its premalignant character that can evolve into a trophoblastic neoplasm, so that in the complete mole it will transform into a neoplasm. CLINICAL CASE: 43-year-old patient who came for consultation due to the fall of her support plane 3 days earlier, with pelvic pain in the hypogastrium, cramping of moderate intensity, without transvaginal bleeding. She reported being pregnant, without remembering the date of her last menstrual period; no prenatal check-up or previous ultrasound. On physical examination the abdomen was found to be globose, at the expense of a hypertrophic uterus measuring 16 x 12 x 10 cm, HGCß concentrations greater than 150,000 mIU/mL. Endovaginal and pelvic ultrasound reported: anteverted, central, enlarged uterus with snowflake-shaped ultrasound image. Diagnosis: hydatidiform mole. Abdominal hysterectomy was indicated, with findings of an enlarged uterus at the expense of complete mole and unaltered adnexa. CONCLUSION: The patient's diagnosis was fortuitous, noticed on ultrasound. The therapeutic approach established for this type of case in older patients with satisfactory parity allowed for a satisfactory evolution and continued follow-up.

Mola hidatiforme parcial con feto vivo sano a término / Partial hydatidiform mole with healthy live fetus reaching term

Resumen ANTECDENTES: El embarazo molar parcial, con feto vivo sano coexistente, es una forma rara de las molas hidatiformes. Debido a los pocos casos reportados se carece de guías que marquen la pauta para la atención médica de estas pacientes. Si bien el riesgo de complicaciones obstétricas en estos casos es alto, un gran porcentaje de las pacientes puede llegar a tener un recién nacido sano. CASO CLÍNICO: Paciente de 29 años, primigesta, con embarazo espontáneo. A las 23.3 semanas se detectó, por ultrasonido, que la placenta tenía múltiples imágenes anecoicas en su interior, un patrón en "racimo de uvas" que sugería un posible embarazo molar. La paciente decidió continuar con el embarazo a pesar de haberle explicado los riesgos obstétricos. Durante el resto del embarazo cursó con hipertensión gestacional y trombocitopenia, quizá gestacional. Se decidió la finalización del embarazo por vía abdominal a las 38 semanas. El reporte histopatológico corroboró el diagnóstico de mola hidatiforme parcial. CONCLUSIÓN: El momento de finalización del embarazo se determina con base en las complicaciones de la madre o el feto. Es importante la adecuada comunicación con la paciente.

Abstract BACKGROUND: Partial molar pregnancy with coexisting healthy living fetus is a rare form of hydatidiform molas. Due to the few reported cases, there is a lack of guidelines for the medical care of these patients. Although the risk of obstetric complications in these cases is high, a large percentage of patients may go on to have a healthy newborn. CLINICAL CASE: A 29-year-old primigravida patient with a spontaneous pregnancy. At 23.3 weeks, the placenta was detected by ultrasound to have multiple anechoic images in its interior, a "cluster of grapes" pattern suggesting a possible molar pregnancy. The patient decided to continue with the pregnancy after the obstetric risks were explained to her. During the remainder of the pregnancy she presented with gestational hypertension and thrombocytopenia, perhaps gestational. It was decided to terminate the pregnancy by abdominal approach at 38 weeks. The histopathological report corroborated the diagnosis of partial hydatidiform mole. CONCLUSION: The timing of termination of pregnancy is determined based on maternal or fetal complications. Adequate communication with the patient is important.

Initial management of hydatidiform mole

Introduction: Hydatidiform mole is a type of gestational trophoblastic disease that results from the abnormal fertilization of an oocyte and causes nonspecific symptoms such as amenorrhea, metrorrhagia, and enlarged uterus. Although rare, its most characteristic symptoms include hyperemesis, early-onset pre-eclampsia, anemia, and respiratory distress. Case presentation: A 47-year-old Moroccan woman consulted the emergency department of the Hospital Clínico Universitario in Valladolid (Spain) after a month of persistent coughing and emesis. The patient reported epigastralgia and amenorrhoea for two months, as well as scant vaginal bleeding two days prior to consultation. Taking into account that the patient tested positive for pregnancy, that a heterogeneous intrauterine mass measuring 124x120mm was observed on transvaginal ultrasound, that no abnormal findings were reported on Doppler ultrasound, and that her serum ßhCG levels reached a value of 772.110 mIU/mL, a diagnosis of hydatidiform mole was suspected. Once informed about the possible therapeutic options, the patient decided to undergo a total hysterectomy, as she stated that she had already fulfilled her desire to be a mother. After the procedure, the patient's clinical condition improved, and the pathology report of the mass confirmed the diagnosis of partial hydatidiform mole. Conclusion: Early diagnosis of hydatidiform mole is paramount in order to provide adequate treatment and improve the prognosis of these patients. Therefore, despite its low incidence and non-specific clinical manifestations, it should be considered as a differential diagnosis for first-trimester metrorrhagia.

Introducción. La mola hidatiforme es un tipo de enfermedad trofoblástica gestacional que se presenta como resultado de la fertilización anormal de un ovocito y que ocasiona síntomas inespecíficos como amenorrea, metrorragia y aumento del tamaño del útero. Aunque infrecuentes, sus síntomas más característicos incluyen hiperémesis, preeclampsia de inicio temprano, anemia y distrés respiratorio. Presentación del caso. Mujer marroquí de 47 años que consultó al servicio de urgencias del Hospital Clínico Universitario de Valladolid debido a que había presentado tos y vómitos por un mes. La paciente refirió haber sufrido epigastralgia y amenorrea por dos meses, así como escaso sangrado vaginal en los últimos dos días. Teniendo en cuenta que la paciente dio positivo en una prueba de embarazo, que en la ecografía transvaginal se observó una masa intrauterina heterogénea de 124x120mm, que no se reportaron hallazgos anormales en la ecografía Doppler y que sus niveles séricos de ßhCG alcanzaron un valor de 772.110 mUI/mL, se sospechó un diagnóstico de mola hidatiforme. Una vez informada sobre las posibles alternativas terapéuticas, la paciente decidió someterse a una histerectomía total, pues refirió que ya había cumplido su deseo de ser madre. Luego de realizar procedimiento, la condición clínica de la paciente mejoró; además, el informe de patología de la masa permitió confirmar el diagnóstico de mola hidatiforme parcial. Conclusiones. El diagnóstico temprano de la mola hidatiforme es de gran importancia para ofrecer un tratamiento adecuado y, de esta forma, mejorar el pronóstico de estas pacientes. Por tanto, a pesar de su baja incidencia y sus manifestaciones clínicas inespecíficas, se debe considerar como diagnóstico diferencial de las metrorragias del primer trimestre.

Telemedicine in post-molar follow-up: is it a useful tool?

BACKGROUND: Telemonitoring is an alternative to in-person appointments and overcomes geographic distance barriers. OBJECTIVE: The primary objective of this study was to evaluate adherence to post-molar follow-up using both WhatsApp and in-person appointments compared with standard care. The secondary objective was to evaluate the rate of completion of post-molar follow-up of complete moles, considering 6 and 3 months of duration. METHODS: This retrospective cohort study was conducted at the Gestational Trophoblastic Disease Center, São Paulo Hospital. Patients with complete or partial mole treatment between January 1, 2009 and December 31, 2018 were included in two groups: group 1 (patients from 2009 to 2013) and group 2 (from 2014 to 2018), before and after telemonitoring implementation, respectively. Complete follow-up was considered if after the first normal human chorionic gonadotropin (hCG) level (<5 mIU/mL), the patient was followed up for an additional 30 days (partial mole) or 180 days (complete mole). Loss to post-molar follow-up with positive hCG was also evaluated. Statistical analysis was performed using Pearson's Χ2 test, 5% significance level (p=0.05), and R version 4.0.2. RESULTS: A total of 308 patients were included in the study, 92 of them were assessed in group 1 and 216 patients in group 2. There was no difference between the rates of complete follow-up after telemonitoring implementation (complete mole: 42/72=58.3% group 1 vs 85/163=52.1% group 2; p=0.38; partial mole: 16/20=80% group 1 vs 37/53=69.8 group 2; p=0.3), and no increase of loss to post-molar follow-up with positive hCG (8/92=8.7% group 1 vs 14/216=6.5% group 2; p=0.49). The shortening of follow-up of complete moles to 90 days increased the rate of complete post-molar follow-up (from 127/235=54.0% to 189/235=80.4%, p<0.001). CONCLUSIONS: The association of telemonitoring with in-person appointments could have had an advantage in post-molar follow-up since it did not reduce adherence to hormonal surveillance. Shortening post-molar follow-up after complete mole to 90 days after the first normal hCG level increased the rate of complete post-molar follow-up.

Clinical characteristics and thyroid function in complete hydatidiform mole complicated by hyperthyroidism.

OBJECTIVES: To identify possible clinical factors associated with hyperthyroidism at presentation and to assess post-evacuation thyroid function in women with complete hydatidiform mole (CHM). METHODS: This observational study included women with CHM attending a specialized Brazilian center in 2002-2018. Clinical and laboratory data (serum hCG, TSH, fT4) were collected at presentation. Factors associated with hyperthyroidism were assessed by logistic regression. Receiver-operating characteristic curves were built to determine the hCG cutoff for predicting hyperthyroidism at CHM presentation. Post-molar evacuation follow-up included clinical assessment and close thyroid function monitoring. RESULTS: Of 137 CHM patients, 69 (50.3%) had hyperthyroidism of any type (43.5% subclinical, 56.5% overt) at presentation. Uterine fundal height > 16 cm or > gestational age (GA), and theca lutein cysts >6 cm were significantly associated with both subclinical and overt hyperthyroidism. The optimal hCG cutoff for predicting hyperthyroidism was 430,559 IU/L (sensitivity 85.5%, specificity 83.8%). Post-evacuation hyperthyroidism/transient hypothyroidism conversion was observed in 13% of the women with hyperthyroidism at presentation. Among the patients not showing conversion to hypothyroidism, median time for TSH normalization was 2 and 3 weeks for subclinical and overt hyperthyroidism, respectively. In the women with overt hyperthyroidism, fT4 was normalized at 2 weeks. CONCLUSIONS: Uterine fundal height > 16 cm, uterine fundal height > GA, theca lutein cysts >6 cm, and hCG >400,000 IU/L at presentation are associated with greater risk of hyperthyroidism and its complications. Close monitoring thyroid function during postmolar follow-up showed that, as thyroid hormones are normalized within 2-3 weeks post-evacuation, the use of beta-blockers or antithyroid drugs can be rapidly discontinued.

Video Hysteroscopy in the Diagnosis of Molar Pregnancy in two Challenging Situations: Complete Mole with Normal hCG and Partial Mole with Early Gestational Age.

STUDY OBJECTIVE: To present the first hysteroscopic findings of 2 cases of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) within the context of the patients' clinical histories. DESIGN: Presentation of 2 hysteroscopic videos with narration of the intrauterine findings of molar pregnancy (MP) from Rio de Janeiro Gestational Trophoblastic Disease Reference Center. SETTING: MP is characterized by abnormal fertilization that generates 2 clinical syndromes: CHM and PHM [1]. INTERVENTIONS: In the first case, the patient was aged 50 years, and hysteroscopy was indicated to assess abnormal uterine bleeding in the presence of normal serum human chorionic gonadotropin (hCG) and transvaginal ultrassonography showing an endometrial cavity with heterogeneous content. Hysteroscopy found translucent hydropic structures diagnosed as CHM. The negative hCG value was due to the hook effect (hCG after dilution: 2 240 000 IU/L). In the second case, an 18-year-old patient underwent hysteroscopy to assess the endometrial cavity with retained abortion at 7 weeks in which, during conservative management, the hCG level increased over 4 weeks from 25 000 IU/L to 58 000 IU/L. Hysteroscopy visualized the embryo with its umbilical cord and hydatidiform vesicles diagnosed as PHM. CONCLUSION: MP can be an incidental finding during hysteroscopy for abnormal uterine bleeding or retained abortion [2-4]. Knowing its morphology during hysteroscopy is helpful for the correct management of this uncommon clinical situation. Hysteroscopy as an adjunct diagnostic tool (not as first-line treatment for MP) can be of significant benefit in challenging clinical scenarios. Further studies should assess the possible risk of spreading molar cells into the peritoneal cavity owing to hysteroscopic fluid.

Distinct microRNA profiles for complete hydatidiform moles at risk of malignant progression.

BACKGROUND: MicroRNAs are small noncoding RNAs with important regulatory functions. Although well-studied in cancer, little is known about the role of microRNAs in premalignant disease. Complete hydatidiform moles are benign forms of gestational trophoblastic disease that progress to gestational trophoblastic neoplasia in up to 20% of cases; however, there is no well-established biomarker that can predict the development of gestational trophoblastic neoplasia. OBJECTIVE: This study aimed to investigate possible differences in microRNA expression between complete moles progressing to gestational trophoblastic neoplasia and those regressing after surgical evacuation. STUDY DESIGN: Total RNA was extracted from fresh frozen tissues from 39 complete moles collected at the time of uterine evacuation in Brazil. In the study, 39 cases achieved human chorionic gonadotropin normalization without further therapy, and 9 cases developed gestational trophoblastic neoplasia requiring chemotherapy. Total RNA was also extracted from 2 choriocarcinoma cell lines, JEG-3 and JAR, and an immortalized normal placenta cell line, 3A-subE. MicroRNA expression in all samples was quantified using microRNA sequencing. Hits from the sequencing data were validated using a quantitative probe-based assay. Significantly altered microRNAs were then subjected to target prediction and gene ontology analyses to search for alterations in key signaling pathways. Expression of potential microRNA targets was assessed by quantitative real-time polymerase chain reaction and western blot. Finally, potential prognostic protein biomarkers were validated in an independent set of formalin-fixed paraffin-embedded patient samples from the United States (15 complete moles progressing to gestational trophoblastic neoplasia and 12 that spontaneously regressed) using quantitative immunohistochemistry. RESULTS: In total, 462 microRNAs were identified in all samples at a threshold of <1 tag per million. MicroRNA sequencing revealed a distinct set of microRNAs associated with gestational trophoblastic neoplasia. Gene ontology analysis of the most altered transcripts showed that the leading pathway was related to response to ischemia (P<.001). Here, 2 of the top 3 most significantly altered microRNAs were mir-181b-5p (1.65-fold; adjusted P=.014) and mir-181d-5p (1.85-fold; adjusted P=.014), both of which have been shown to regulate expression of BCL2. By quantitative real-time polymerase chain reaction, BCL2 messenger RNA expression was significantly lower in the complete moles progressing to gestational trophoblastic neoplasia than the regressing complete moles (-4.69-fold; P=.018). Reduced expression of BCL2 was confirmed in tissue samples by western blot. Immunohistochemistry in the independent patient samples revealed significantly lower cytoplasmic expression of BCL2 in the villous trophoblasts from cases destined for progression to gestational trophoblastic neoplasia compared with those that regressed, both with respect to staining intensity (optic density 0.110±0.102 vs 0.212±0.036; P<.001) and to the percentage of positive cells (16%±28% vs 49.4%±28.05%; P=.003). CONCLUSION: Complete moles progressing to gestational trophoblastic neoplasia are associated with a distinct microRNA profile. miR-181 family members and BCL2 may be prognostic biomarkers for predicting gestational trophoblastic neoplasia risk.

Fatores citogenéticos associados a danos reprodutivos em programa universitário de genética comunitária / Cytogenetic factors associated with reproductive damage in community genetics university programs

Introdução: perdas gestacionais esporádicas são comuns e estima-se que aproximadamente 30 a 50% de todas as concepções não terminem em um recém-nascido vivo. Patologia materna ou alteração genética de natureza cromossômica, em um dos progenitores, são fatores de risco favoráveis a esses acontecimentos. Outras situações que podem estar relacionadas às alterações cromossômicas são a infertilidade e a ocorrência de mola hidatiforme (neoplasia trofoblástica gestacional), caracterizada por interferência na formação e desenvolvimento do embrião. Embora haja um consenso sobre o caráter multifatorial das perdas gestacionais, incluindo componentes anatômicos, imunológicos, endócrinos, genéticos e ambientais, ainda assim, a causalidade pode permanecer desconhecida. Objetivos: analisar e quantificar achados de dificuldades reprodutivas relacionados a presença de alterações cromossômicas encontrados no serviço de genética realizado pelo programa Genética & Sociedade, do Instituto de Biologia da Universidade Federal da Bahia. Metodologia: estudo descritivo e analítico, realizado por meio de consulta a fichas de anamneses, preenchidas durante o atendimento de casais, que buscaram o serviço de genética comunitária para aconselhamento genético no período de vinte anos. Resultados: entre os 73 casais selecionados para estudo, 59 (80,8%) relataram abortos recorrentes, 9 (12,3%) tinham histórico de mola hidatiforme e 5 (6,8%) apresentaram infertilidade. Entre as alterações foram verificadas translocações, inversões, além de polimorfismos de regiões heterocromáticas. Conclusões: o presente estudo confirma a importância das alterações cromossômicas na etiologia das dificuldades reprodutivas, justificando a busca pelo aconselhamento genético. Em termos de saúde pública, traz contribuições para o entendimento das condições genéticas da comunidade beneficiada pelo programa Genética & Sociedade.

Introduction: sporadic gestational losses are common, it's estimated that approximately 30 to 50% of all conceptions don't end in a newborn alive. Maternal pathology or genetic alterations of chromosomal nature in one of the progenitors are risk factors favorable to these events. Other situations that may be related to chromosomal alterations are infertility and the occurrence of hydatidiform mole (gestational trophoblastic neoplasia), characterized by interference in the formation and development of the embryo. Although there is a consensus about the multifactorial nature of gestational losses, including anatomical, immunological, endocrine, genetic and environmental components, however, the causality may remain unknown. Objectives: analyze and quantify the findings of reproductive difficulties related to the presence of chromosomal alterations found in the genetics service performed by the Genética&Sociedade program of the Biology Institute of the Federal University of Bahia. Methodology: a descriptive and analytical study, carried out by consultation of anamnesis records, made during the care of couples, who sought the community genetic service for genetic counseling in the period of twenty years. Results: among the 73 couples selected, 59 (80.8%) reported recurrent abortions, 9 (12.3%) had a history of hydatidiform mole and 5 (6.8%) had infertility. Among all the alterations, were found translocations, inversions, and polymorphisms of heterochromatic regions. Conclusions: this study confirms the importance of chromosomal alterations in the etiology of reproductive difficulties, justifying the search for genetic counseling. In terms of public health, it contributes to the understanding of the genetic conditions in the community benefited by the Genética&Sociedade program.

Mola invasiva coexistente con feto vivo normal. Reporte de caso / Invasive hydatidiform mole coexistent with normal fetus. Case report

RESUMEN Comunicamos el caso de una gestante referida por sospecha de mola parcial. Las imágenes ultrasonográficas mostraban un feto normal unido a placenta pequeña, adyacente a una masa tumoral en 'panal de abejas'. Se realizó amniocentesis, con resultado de cariotipo normal. Debido a valores de hCG-β superiores a 800 000 UI y crecimiento de la masa de 11% a la resonancia magnética, se realizó biopsia tumoral percutánea guiada por ecografía, la cual alejó la posibilidad de coriocarcinoma. La paciente hizo síntomas de hipertiroidismo que requirieron tratamiento y, al superar la hCG-β el millón de unidades, se decidió dar un curso de quimioterapia. A las 29 semanas inició trabajo de parto; se realizó cesárea-histerectomía, obteniéndose recién nacido vivo, con Apgar 5 y 7. Al examen anatomopatológico, la masa placentaria resultó mola invasiva. De acuerdo con nuestra búsqueda, se comunica el primer caso en la literatura de coexistencia de mola invasiva con feto sano, y resaltamos la importancia de usar las herramientas diagnósticas y de manejo necesarias para lograr la viabilidad del producto de la concepción, sin incrementar el riesgo materno.

ABSTRACT We report the case of a pregnant woman referred to our hospital for suspected partial hydatidiform mole. Ultrasound images showed a normal fetus attached to a small placenta adjacent to a honeycomb-like tumor mass. Amniocentesis revealed a normal karyotype. Due to β-hCG values greater than 800 000 IU and a mass growth of 11% by magnetic resonance imaging, an ultrasound-guided percutaneous tumor biopsy was performed; it ruled out the possibility of choriocarcinoma. The patient had symptoms of hyperthyroidism that required treatment; when the β-HCG levels exceeded one million IU, a course of chemotherapy was prescribed. At 29 weeks, the patient started labor; a cesarean hysterectomy was performed, obtaining a live newborn with Apgar 5 and 7. The pathology report informed the placental mass as an invasive mole. According to our literature search, this is the first case report where an invasive mole coexisted with a healthy fetus. We highlight the importance of using all diagnostic and management tools necessary to achieve fetal viability, without increasing the maternal risk of complications.

Factores asociados a enfermedad trofoblástica gestacional en el Hospital Hipólito Unánue durante el período de enero del 2014 a diciembre del 2018 / Factors Associated With Gestational Trophoblastic Disease At The Hipólito Unánue Hospital During The Period From January 2014 To December 2018

Objetivo: Determinar los factores de riesgo asociados a enfermedad trofoblástica gestacional en pacientes atendidas en consultorio externo del servicio de Ginecobstetricia del Hospital Nacional Hipólito Unanue entre enero 2014 y diciembre del 2018. Métodos: Se realizó un estudio observacional, retrospectivo, analítico de tipo casos y controles. Se tomó como muestra un total de 60 casos y se revisaron 120 historias como grupo control. La información obtenida de la revisión de historias clínicas fue registrada en la ficha de recolección de datos. Se determinó el odds ratio con sus respectivos intervalos de confianza (IC=95%). Para el análisis multivariado se empleó un modelo de regresión logística binaria. Resultados: En el análisis bivariado los factores asociados a enfermedad trofoblástica gestacional fueron el antecedente de aborto (OR 6,54; IC 95% 3.12 - 13.74; p <0.001) y la multiparidad (OR 3.35; IC 95%: 1.47 - 7.65; p <0,001). La edad menor a 20 años se asoció a una menor frecuencia (OR: 0.13; IC: 0.03-0.48 p<0.001). En el análisis multivariado las únicas variables que mostraron significancia fueron el antecedente de aborto (OR 4.85; IC95% 1.82-12.91; p=0.002) como factor de riesgo y la edad menor a 20 años como factor protector (OR 0.08; IC95% 0.02-0.32; p<0.001). Conclusión: El antecedente de aborto y la multiparidad se asociaron a la presencia de enfermedad trofoblástica gestacional, mientras que la edad menor a 20 años se comportó como un factor protector.

Objective: To determine the risk factors associated with gestational trophoblastic disease in patients treated in an outpatient office of the Gynecobstetrics service of the National Hospital Hipólito Unanue between January 2014 and December 2018. Methods: An observational, retrospective, analytical study of cases and controls was conducted. A total of 60 cases were taken as a sample and 120 stories were reviewed as a control group. The information obtained from the review of medical records was recorded in the data collection form. The odds ratio was determined with their respective confidence intervals (CI = 95%). For the multivariate analysis, a binary logistic regression model was used. Results: In the bivariate analysis, the factors associated with gestational trophoblastic disease were the history of abortion (OR 6.54; 95% CI 3.12 - 13.74; p <0.001) and multiparity (OR 3.35; 95% CI: 1.47 - 7.65; p <0.001). Age under 20 years was associated with a lower frequency (OR: 0.13; CI: 0.03-0.48 p <0.001). In the multivariate analysis, the only variables that showed significance were the history of abortion (OR 4.85; 95% CI 1.82-12.91; p = 0.002) as a risk factor and age under 20 years as a protective factor (OR 0.08; 95% CI 0.02 -0.32; p <0.001). Conclusion: The history of abortion and multiparity were associated with the presence of gestational trophoblastic disease, while the age under 20 years behaved as a protective factor.

Factores asociados a enfermedad trofoblástica gestacional en un hospital de referencia peruano / Factors associated with gestational trofoblastic disease in a peruvian reference hospital

RESUMEN Objetivo : Determinar los factores de riesgo asociados a enfermedad trofoblástica gestacional en pacientes atendidas en consultorio externo del servicio de ginecobstetricia del Hospital Nacional Hipólito Unanue entre enero 2014 y diciembre del 2018. Métodos : Se realizó un estudio observacional, retrospectivo, analítico de tipo casos y controles. Se tomó como muestra un total de 60 casos y se revisaron 120 historias como grupo control. La información obtenida de la revisión de historias clínicas fue registrada en la ficha de recolección de datos. Se determinó el odds ratio con sus respectivos intervalos de confianza (IC=95%). Para el análisis multivariado se empleó un modelo de regresión logística binaria. Resultados : En el análisis bivariado los factores asociados a enfermedad trofoblástica gestacional fueron el antecedente de aborto (OR 6,54; IC 95% 3,12 - 13,74; p <0,001) y la multiparidad (OR 3,35; IC 95%: 1,47 - 7,65; p <0,001). La edad menor a 20 años se asoció a una menor frecuencia (OR: 0,13; IC: 0,03-0,48 p<0,001). En el análisis multivariado las únicas variables que mostraron significancia fueron el antecedente de aborto (OR 4,85; IC95% 1,82-12,91; p=0.002) como factor de riesgo y la edad menor a 20 años como factor protector (OR 0,08; IC95% 0,02-0,32; p<0,001). Conclusiones El antecedente de aborto y la multiparidad se asociaron a la presencia de enfermedad trofoblástica gestacional, mientras que la edad menor a 20 años se comportó como un factor protector.

ABSTRACT Objective : To determine the risk factors associated with gestational trophoblastic disease in patients treated in an outpatient office of the Gynecobstetrics service of the National Hospital Hipólito Unanue between January 2014 and December 2018. Method : An observational, retrospective, analytical study of cases and controls was conducted. A total of 60 cases were taken as a sample and 120 stories were reviewed as a control group. The information obtained from the review of medical records was recorded in the data collection form. The odds ratio was determined with their respective confidence intervals (CI = 95%). For the multivariate analysis, a binary logistic regression model was used. Results : In the bivariate analysis, the factors associated with gestational trophoblastic disease were the history of abortion (OR 6.54; 95% CI 3.12 - 13.74; p <0.001) and multiparity (OR 3.35; 95% CI: 1.47 - 7.65; p <0.001). Age under 20 years was associated with a lower frequency (OR: 0.13; CI: 0.03-0.48 p <0.001). In the multivariate analysis, the only variables that showed significance were the history of abortion (OR 4.85; 95% CI 1.82-12.91; p = 0.002) as a risk factor and age under 20 years as a protective factor (OR 0.08; 95% CI 0.02 -0.32; p <0.001). Conclusions : The history of abortion and multiparity were associated with the presence of gestational trophoblastic disease, while the age under 20 years behaved as a protective factor.

Mola invasiva en adolescente de 13 años. Aspectos fundamentales del diagnóstico y tratamiento / Invasive mola in 13-year-old girl. Fundamental aspects in diagnosis and treatment

Resumen ANTECEDENTES: La neoplasia gestacional trofoblástica es un tumor raro, derivado de la gestación que procede de un desarrollo anormal del tejido trofoblástico. Incluye cuatro variedades, entre las que se encuentra la mola invasiva y el coriocarcinoma. Puede tener diferentes grados de proliferación; el diagnóstico diferencial es decisivo porque influye directamente en el tratamiento. Las molas premalignas suelen tratarse con legrado uterino, las malignas requieren tratamiento sistémico con mono o poliquimioterapia. CASO CLÍNICO: Paciente de 13 años, hospitalizada debido a un cuadro de vómitos y dolor abdominal. Durante el internamiento se le practicaron estudios complementarios: determinación de la fracción β de la gonadotropina coriónica humana (β-hCG) y tomografía axial computada para plantear el diagnóstico diferencial. El diagnóstico definitivo lo aportó la biopsia obtenida mediante legrado. El tratamiento se basó en la poliquimioterapia. En la actualidad está en remisión completa de la enfermedad. CONCLUSIONES: Resulta imprescindible detectar lo más temprano posible la gestación anómala, entender perfectamente su evolución e importancia de la anticoncepción mientras se trata y la enfermedad desaparece y minimizar la cantidad de pacientes que deben recibir quimioterapia.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is a rare tumor that originates from pregnancy and it develop from anormal proliferation of trophoblastic tissue. It includes four varieties, including invasive mole and choriocarcinoma. They can present different degrees of proliferation, being essential differential diagnosis since it directly influences the treatment. Premalignant moles are usually treated by suction curettage while malignant forms require systemic therapy with mono or polychemotherapy. OBJECTIVE: Report the case, paying special attention to the differential diagnosis and treatment used, analyzing the reasons why polychemotherapy is established and describing the different possible options, based on current scientific evidence. CLINICAL CASE: We present the case of an invasive mola in a 13-year-old patient hospitalized by vomiting and abdominal pain. During this period, complementary techniques such as the determination of the β fraction of the human chorionic gonadotropin (β-hCG) or computed tomography (CT) are required to establish the differential diagnosis. Finally, the definitive diagnosis is provided by the biopsy obtained by curettage. Treatment is instituted with the pattern of polychemotherapy being, currently, with complete remission of the disease. CONCLUSIONS: Thus, it is essential to detect anomalous gestation early, to understand perfectly the evolution of this entity, the importance of contraception during its resolution, and to minimize patients susceptible to chemotherapy.

Association between antioxidant vitamins and oxidative stress among patients with a complete hydatidiform mole

OBJECTIVES: This study aimed to evaluate the potential relationship between oxidative stress, dietary intake, and serum levels of antioxidants in patients with a complete hydatidiform mole (CHM) compared with controls. METHODS: This was an observational cross-sectional study conducted in Rio de Janeiro, Brazil. A total of 140 women were enrolled in this study and divided into four groups: 43 patients with CHM, 33 women who had had an abortion, 32 healthy pregnant women, and 32 healthy non-pregnant women. All participants underwent blood sampling, assessment using a semiquantitative food frequency questionnaire, and anthropometric measurement. Blood samples were collected after overnight fasting (10-12 h). Vitamin levels (A, C, and E) were determined by ultra-performance liquid chromatography, and gamma-glutamyl transferase levels were assessed using an automated quantitative analysis system (Dimension®, Siemens). RESULTS: Although all groups showed sufficient serum vitamin A and E levels, the participants had inadequate dietary intake of these vitamins. Conversely, all groups had an insufficient serum level of vitamin C, despite adequate intake. The gamma-glutamyl transferase values did not differ significantly among the groups. However, elevated serum levels of this enzyme were observed in several patients. CONCLUSIONS: All groups exhibited high levels of oxidative stress, as evaluated by gamma-glutamyl transferase levels, and had inadequate intake of antioxidant vitamins. Therefore, the high exposure to oxidative stress found in our study, even in healthy pregnant and non-pregnant women, may increase the incidence of CHM in this region.