Manejo de la neoplasia trofoblástica gestacional. A propósito de un caso

La enfermedad trofoblástica gestacional es definida como un grupo heterogéneo de lesiones, las cuales surgen a partir del epitelio trofoblástico de la placenta luego de una fertilización anormal. Se presenta el caso de una paciente de 35 años de edad, con diagnóstico de neoplasia trofoblástica gestacional posmolar en etapa I, que se detectó tras estudios imagenológicos de seguimiento y determinación de la hormona gonadotropina coriónica humana, para lo cual llevó tratamiento con quimioterapia y terapéutica de mantenimiento con metotrexato por 5 días o metotrexato/ácido folínico por 8 días, hasta la normalización de la gonadotropina coriónica humana. Lo más relevante es que, aunque estos tumores abarcan menos del 1 % de los tumores ginecológicos, representan una amenaza para la vida de las mujeres en edad reproductiva.

Gestational trophoblastic disease is defined as a heterogeneous group of lesions, which arise from the trophoblastic epithelium of the placenta after abnormal fertilization. The case of a 35-year-old female patient is presented with a diagnosis of posmolar gestational trophoblastic neoplasia in stage I, which was detected after follow-up imaging studies and determination of human chorionic gonadotropin, for which she underwent chemotherapy treatment and maintenance therapy with methotrexate for 5 days or methotrexate/folinic acid for 8 days, until normalization of human chorionic gonadotropin The most relevant thing is that, although these tumors comprise less than 1% of gynecological tumors, they represent a threat to the life of women of reproductive age.

Correlation of uterine artery Doppler flow velocimetry and β-human chorionic gonadotropin levels during postmolar evacuation surveillance: A pilot study in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Background@#During postmolar evacuation surveillance, beta-human chorionic gonadotropin (β-hCG) regression levels can predict invasive disease while Doppler ultrasound can assess in vivo tumor neovascularization and quantify uterine blood supply. As an ancillary tool to β-hCG monitoring, ultrasound can detect the early presence of viable trophoblastic tissues and identify patients at risk of developing postmolar gestational trophoblastic Neoplasia (PMGTN). @*Objective@#The objective of this study was to correlate uterine artery Doppler ultrasound with β-hCG levels during pre- and postmolar evacuation surveillance among patients with complete mole.@*Materials and Methods@#A cohort of patients with sonographic diagnosis of complete hydatidiform mole and managed with suction curettage in the same institution were prospectively followed up after evacuation. The pre- and postmolar evacuation surveillance period was at days 1, 7, 14, 21, 28, and 35. Monitoring of serum β-hCG levels was based on the standard regression curve. For Doppler ultrasound parameters, monitoring of the systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) was based on its relationship with its serum β-hCG levels. The ultrasound images generated were archived and reviewed by the authors. Descriptive and inferential statistics were utilized to analyze median differences. For the correlation of uterine artery Doppler flow parameters, analysis for the test of difference used Pearson correlation and multiple linear regression analysis for the odds ratio.@*Results@#Sixteen of the 23 enrolled patients completed the protocol (16 of 23, 69.50%). A majority had spontaneous remission (13; 81%) while 3 cases (19%) presented increasing and plateauing β-hCG levels. The pre- and post evacuation median β-hCG levels showed a significant decrease (P = 0.001). As post evacuation β-hCG levels decreased, PSV also decreased (r = 0.478, P = 0.061) while Doppler parameters, RI, PI, and S/D ratio increased. However, when post evacuation β-hCG levels rose or plateaued, Doppler parameters decreased. These changes had statistical correlation (all P < 0.05). Moreover, the magnitude of the relationship for β-hCG and Doppler parameters was moderate and ranged from 0.524 to 0.581. Among the Doppler parameters, the S/D ratio and RI of the right uterine artery strongly predicted a rise in β-hCG levels. The odds ratio of predicting increased β-hCG levels and risk of gestational trophoblastic neoplasia by the right S/D ratio were − 2683.67 (confidence interval [CI] = −271.692–5095.655; P = 0.034) and by the right RI − 66,193.34 (CI = −161,818.107–29,431.433; P = 0.046). Notably, Doppler parameter changes appeared early at day 14 up to day 35 and before the appearance of abnormal β-hCG regression patterns.@*Conclusion@#There is a strong correlation between uterine artery Doppler flow changes and β-hCG levels during postmolar evacuation surveillance. The inverse relationship of the S/D ratio, PI and RI, and β-hCG regression patterns confirms spontaneous remission of the disease. For patients with abnormal β-hCG patterns, this relationship is altered. The Doppler changes become erratic, unpredictable, and significantly decreased. These changes were detected as early as 2 weeks post evacuation. Thus, the use of ultrasound as an adjunct to β-hCG post evacuation surveillance can predict abnormal β-hCG regression patterns and identify patients at risk of developing postmolar gestational trophoblastic neoplasia (PMGTN).

Tumor trofoblástico de sitio placentario secundario a mola parcial. Reporte de un caso / Placental site trophoblastic tumor secondary to partial mole. Report of a case

Resumen ANTECEDENTES: La enfermedad trofoblástica gestacional es un padecimiento que incluye un grupo de tumores placentarios, consecuencia de una proliferación anormal del tejido del trofoblasto. Se caracteriza por una excesiva elevación de la gonadotrofina coriónica humana que se considera diagnóstica y un predictor pronóstico. CASO CLÍNICO: Paciente de 23 años con hiperémesis gravídica y aumento del tamaño del útero mayor para las siete semanas de gestación y cuantificación de las concentraciones de HGC anormalmente elevadas en comparación con su valor basal. Se descartaron los diagnósticos diferenciales de mola parcial hidatiforme, mola completa y embarazo múltiple. Se concluyó que se trataba de enfermedad trofoblástica gestacional. Se procedió a la evacuación de la cavidad uterina de la que se extrajeron abundantes porciones de tejido ovoconformacional y molariforme. El informe de Patología fue: útero arcuato con tumor de sitio placentario, endometritis crónica, cervicitis con metaplasia escamosa, quiste de Nabot y endometrio proliferativo tardío. CONCLUSIÓN: Puesto que las pacientes con enfermedad trofoblástica gestacional suelen tener un pronóstico sombrío se sugiere la histerectomía simple para llegar a la curación. Por la agresividad del tumor y resistencia a otros tratamientos es indispensable el monitoreo riguroso semanal de la cuantificación de la HCG.

Abstract BACKGROUND: Gestational trophoblastic disease is a condition that includes a group of placental tumors resulting from abnormal proliferation of trophoblast tissue. It is characterized by an excessive elevation of human chorionic gonadotropin which is considered diagnostic and a prognostic predictor. CLINICAL CASE: 23-year-old patient with hyperemesis gravidarum and uterine enlargement greater than 7 weeks' gestation and abnormally elevated HGC levels compared to baseline. The differential diagnoses of hydatidiform partial mole, complete mole and multiple pregnancy were ruled out. It was concluded that it was gestational trophoblastic disease. The uterine cavity was evacuated and abundant portions of ovoconformal and molariform tissue were extracted. The pathology report was: arcuate uterus with placental site tumor, chronic endometritis, cervicitis with squamous metaplasia, Nabot's cyst and late proliferative endometrium. CONCLUSION: Since patients with gestational trophoblastic disease usually have a dismal prognosis simple hysterectomy is suggested to reach cure. Because of the aggressiveness of the tumor and resistance to other treatments, rigorous weekly monitoring of HCG quantification is indispensable.

Effect of follicular size on clinical outcomes of frozen-thawed embryo transfer induced by hCG on ovulation in natural cycles / 中华妇产科杂志

Objective:To investigate the effect of follicular size on the clinical outcomes of frozen-thawed embryo transfer induced by human chorionic gonadotropin (hCG) of natural cycles on ovulation.Methods:Clinical data of 427 cycles of frozen-thawed single blastocyst transfer in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively analyzed. The patients were divided into 15-16 mm group (15≤diameter≤16 mm, n=66), 16-17 mm group (16<diameter≤17 mm, n=101), 17-18 mm group (17<diameter≤18 mm, n=125), 18-20 mm group (18<diameter≤20 mm, n=109),>20 mm group (diameter>20 mm, n=26), according to the maximum follicle diameter on the induction day of hCG ovulation induction. The estradiol and luteinizing hormone (LH) levels, and clinical pregnancy rate, abortion rate and live birth rate were compared in five groups. Results:There were statistically significant differences in estradiol and LH levels among the five groups on the day of hCG induction (all P<0.05). Estradiol levels in 15-16 mm group to >20 mm group gradually increased on the day of hCG induction, and estradiol level in 15-16 mm group was significantly lower than those in 17-18 mm group, 18-20 mm group and >20 mm group (median: 1 002.3 vs 1 103.3 vs 1 171.2 vs 1 539.0 pmol/L), with statistical significances ( P=0.034, P<0.001, P=0.002). On the day of hCG induction, LH levels in 15-16 mm group to >20 mm group showed a decreasing trend, and LH level in 15-16 mm group was significantly higher than those in 17-18 mm group and >20 mm group (median: 37.73 vs 28.24 vs 24.11 U/L), with statistically significant differences ( P=0.007, P=0.006). There were no significant differences in clinical pregnancy rate, abortion rate and live birth rate in 15-16 mm group to >20 mm group (all P>0.05). Conclusion:In the natural cycle protocol of hCG induced ovulation, the small follicle group could achieve similar clinical outcomes compared with normal sized follicles in the single blastocyst transfer of frozen-thawed embryos.

Association of ultrasound morphological features with serum β subunit human chorionic gonadotrophin and histopathology among sonologically diagnosed cases of gestational trophoblastic neoplasia in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Background@#Gestational trophoblastic neoplasia (GTN) presents as vascular mass of varying morphology on ultrasound and confirmed through quantitative serum β subunit human chorionic gonadotrophin (β‑hCG). In regions with limited access to β‑hCG, ultrasound plays a crucial role in the initial diagnosis for timely management.@*Objectives@#This study aimed to investigate the associations between ultrasound vascular morphologic features, serum β‑hCG levels, and histopathology in GTN cases.@*Methodology@#A cross‑sectional review was conducted on 113 cases with ultrasound impression of GTN over an 8‑year period. The patient data were extracted from case records, and ultrasound images were categorized based on the distinct features. Associations with β‑hCG levels and histopathology were analyzed using the Chi‑square test and Mann–Whitney U‑test. Statistical significance was set at P < 0.05.@*Results@#A significant association was observed between ultrasound category and serum β‑hCG (P < 0.0001). The compact and diffuse types were more prevalent with β‑hCG levels between 104 to <105 mIU/mL, while the lacunar type was common among patients with ≥105 mIU/mL. However, there was no significant association between ultrasound categories and mean β‑hCG levels. Regarding histopathology, the lacunar type was more common in invasive moles, whereas the compact and diffuse types tended to be seen with choriocarcinoma, although these were not statistically significant (P = 0.182).@*Conclusions@#Morphologic types of GTN by gray scale and Doppler ultrasound vary across the different levels of serum β‑hCG and may suggest the histopathological diagnosis. This study provides valuable insights into the ultrasonographic characteristics of GTN, which can aid in its diagnosis and management.

Comparison of beta‑human chorionic gonadotropin‑based prognostic models on the clinical outcomes of gestational trophoblastic disease patients in the Philippines / Philippine Journal of Obstetrics and Gynecology

Objective@#Despite the widespread use and measurement of beta‑human chorionic gonadotropin (β‑HCG) among hydatidiform mole (HM) patients, models derived from this biomarker to predict the remission or postmolar gestational trophoblastic neoplasia (GTN) rarely perform well. The study aimed to generate cutoff points for postevacuation β‑HCG levels and evaluate their performance among women with complete molar pregnancies@*Methods@#A retrospective cohort study composed of women with complete HM underwent bivariate procedures comparing characteristics between the comparison groups. Cut points using Liu’s and Youden’s indices were estimated, and their performance was evaluated using receiver operating characteristic curve analysis. Cox regression to compare time‑to‑progression across these proposed β‑HCG cutoffs was also performed.@*Results@#The incidence of postmolar GTN among the 155 women in the study was 15.5% (95% confidence interval: 10.2%–22.2%). Postevacuation HCG levels had a better prediction of disease status than preevacuation and HCG ratio models (χ2 : 163.07, P < 0.01). A cutoff at 508 mIU/mL the 3rd‑week postevacuation (area under the curve [AUC]: 0.89, sensitivity: 87.5%, specificity: 90.1%) was comparable with the 185 mIU/mL cutoff at the 5th‑week postevacuation (AUC: 0.89, sensitivity: 91.7%, specificity: 87%). The hazards ratio of postmolar GTN was 29.74 (8.53–103.71) and 39.89 (8.82–180.38) for the 3rd and 5th weeks HCG after evacuation adjusting for clinically relevant variables@*Conclusion@#The first 3rd‑ and 5th‑week postevacuation levels of β‑HCG demonstrated potential in predicting postmolar GTN. However, further refinement and adjustment for clinically relevant risk factors are still needed.

Double trouble in an ectopic pregnancy / Philippine Journal of Obstetrics and Gynecology

@#Gestational trophoblastic diseases are histologically different types of tumors originating from the placenta with an incidence of 0.2–5.8/1000 pregnancies. Ectopic pregnancy is the implantation of the fertilized ovum outside the uterine cavity, and a 0.64% incidence is reported. Ectopic cornual pregnancy and molar pregnancy are rare cases, and a combination of these two rare entities occurring simultaneously is even rare and very few cases have been reported in the literature. A cornual pregnancy refers to the implantation and development of a gestational sac in one of the upper and lateral portions of the uterus, whereas an interstitial pregnancy is a gestational sac that implants within the proximal, intramural portion of the fallopian tube that is enveloped by the myometrium. We present one of the rare combinations of molar pregnancy and cornual/interstitial ectopic pregnancy in a 30‑year‑old G3 P1 who presented with a triad of amenorrhea, vaginal bleeding, and abdominal pain. Laparotomy was done in view of an ultrasound which was suggestive of a well‑defined complex thick‑walled lesion of size 3.2 × 3.3 with a gestational sac and no cardiac activity in the right fallopian tube/adnexa suggesting tubal ectopic pregnancy. Beta‑human chorionic gonadotropin (β‑hCG) levels were done and noted to be as high as 9998 mIU/mL. Intraoperatively, a cornual ectopic pregnancy was found with no hemoperitoneum which was excised. Histopathology showed chorionic villi with variable size and hydropic change, myxoid stromal changes, and cistern formation with polar trophoblastic proliferation, based on which a diagnosis of molar pregnancy was made. Although ultrasonography and higher than usual serum β‑hCG levels are diagnostic of uterine molar pregnancy, they do not yield a proper diagnosis in ectopic molar pregnancy, hence, making it difficult to distinguish between an early ectopic molar pregnancy from a nontrophoblastic tubal pregnancy. The final diagnosis is usually made only after histopathology. A high degree of clinical suspicion of cornual pregnancy followed by histopathological examination of the products of conception is the standard for arriving at an appropriate diagnosis. Serial serum β‑hCG level follow‑up is recommended to rule out its malignant potential.

Correlation Between Blastocyst Morphology Score， Early Serum β-hCG Concentrations and Live Birth After Thawed Single Blastocyst Transfer / 中山大学学报(医学科学版)

ObjectivesTo assess the correlation between blastocyst morphology score， serum human chorionic gonadotropin β subunit （β-hCG） levels on day 12 after transfer and live birth outcomes among cycles tested HCG-positive after thawed single blastocyst transfer； to analyze the predictive value of serum β-hCG levels on live birth. MethodsWe reviewed the data of 519 frozen-thawed single blastocyst transfer cycles （FET） that had been tested HCG-positive from January 2016 to May 2020 at our IVF center. These FET cycles were firstly divided into 4 groups （AA， AB， BA， and BB） according to Gardner's grading system of inner cell mass （ICM） and trophectoderm cell （TE）， and then 4 groups （stages 3， 4， 5 and 6） according to the degree of blastocyst expansion. Serum β-hCG concentrations on day 12 after transfer and live birth rates were compared among groups transferred with different blastocysts grading and expansion stage. The relationship between Gardner’s grading or expansion stage of blastocysts and serum β-hCG levels was determined by correlation test， and ROC curves were plotted to determine the threshold values of serum β-hCG for predicting live birth. Results（1） The serum β-hCG concentration in the AA group and AB group on the 12th day after the transfer was significantly higher than that in the BB group （P <0.001， P <0.001）. However， there was no significant difference in the live birth rate when different ICM/TE-graded blastocysts were transferred （P = 0.120）. There were no significant differences in serum β-hCG concentration on day 12 after transfer and live birth rate among blastocysts with different expansion stages （P = 0.091， P = 0.557）. （2） There was a significant weak correlation between blastocyst ICM/TE grading and serum β-hCG concentration on day 12 （rs = -0.221， P <0.001）， and even after controlling for confounding factors （ rs = -0.228， P <0.001）；There was no significant correlation between blastocyst’s expansion stage and serum β-hCG concentration on day 12 after the transfer （rs = -0.052， P = 0.240）， and the association remained insignificant after controlling for confounding factors （rs = -0.029， P = 0.508）. （3） ROC curve analysis showed that the cut-off value for predicting live birth by serum β-hCG on day 12 was 657.5 mU/mL （P < 0.001）. ConclusionsNeither the ICM/TE grade nor the expansion stage of blastocysts affect the live birth rate，there is significant difference in the level of β-hCG produced by blastocyst with different ICM/TE grade；Our results suggest that early serum β-hCG level can predict live birth.

Histomorphological Analysis of Gestational Trophoblastic Disease Spectrum with Clinicopathological Correlation at a Teaching Hospital

Introduction: Clinically, all trophoblastic lesions are frequently combined under a broad spectrum of gestational trophoblastic diseases (GTDs)without the use of specific pathological terms. However, studies now demonstrate that various forms of GTDs demonstrate differences in etiology, histogenesis, morphology, and clinical behavior. Thus, the need for diagnostic histopathology of these lesions to distinguish gestational trophoblastic neoplasms from nonneoplastic lesions and molar pregnancies and also for early anticipation for early anticipation, risk category stratification, prognostication, management, and prediction of persistent GTD. Our study aimed to study the histomorphological patterns of various types of GTD with light microscopy and the pattern of occurrence of GTDs in relation to age, parity, and gestation. MaterialsandMethods: The present study was conducted in the department of pathology, from January 2020 to April 2022. All GTDs confirmed by histopathological examination by hematoxylin‑ and eosin‑stained slides were included. Results: The spectrum of GTDs found in this study was seventy cases of hydatidiform mole (92.10%), three cases of exaggerated placental site (EPS) reaction (3.94%), and two cases of choriocarcinoma (2.63%) and one case (1.31%) of placental site trophoblastic tumor (PSTT). The most common presenting symptom was vaginal bleeding (93.42%). Conclusion: Hydatidiform mole forms the most common type of GTD with an incidence of complete moles more than partial moles. Histomorphological examination and analysis are helpful for confirmatory diagnosis. The most common clinical presentation of GTD was vaginal bleeding followed by amenorrhea. Emphasis on detailed descriptive morphological assessment can help in the histological distinction of benign lesions such as EPS reaction and placental site nodule and avert such cases from being erroneously diagnosed as neoplastic. The Ki‑67 proliferation index helped in distinguishing the EPS reaction from neoplastic lesions such as PSTT which requires surgical intervention and chemotherapy.

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.

Embarazo ectópico roto con fracción beta de la hormona gonadotropina coriónica humana negativa: reporte de caso / Ruptured ectopic pregnancy with negative human chorionic gonadotropin hormone beta fraction: case report

Resumen El embarazo ectópico roto es una emergencia quirúrgica cuyo diagnóstico, gracias a la interrelación de la cuantificación de la fracción beta de la hormona gonadotropina coriónica humana (HCG-β) y los hallazgos ultrasonográficos, se ha hecho más preciso. Sin embargo, el diagnóstico se vuelve difícil cuando clínicamente se encuentran datos sugestivos de embarazo ectópico con una HCG-β negativa. Presentamos el caso de una mujer de 25 años acude a valoración por referir 12,2 semanas de retraso menstrual, asociado a sangrado transvaginal y signos de irritación peritoneal, que cuenta con HCG-β negativa (< 5 mUI/ml). Se realizó un rastreo ultrasonográfico encontrando abundante líquido libre en cavidad, sin evidencia de embarazo intrauterino. Ante la alta sospecha de embarazo ectópico se realizó laparotomía exploradora, encontrando hallazgos sugestivos de embarazo ectópico roto, y se realizó salpingectomía. Finalmente, en el estudio posoperatorio se confirmó por histopatología un embarazo ectópico roto. Existen muy pocos reportes en la literatura internacional de pacientes con características clínicas de embarazo ectópico roto, con HCG-β negativa. Es importante la difusión de este tipo de casos con la finalidad de mejorar los abordajes diagnósticos y no restar importancia ante la sospecha clínica, a pesar de presentar una HCG-β negativa.

Abstract Broken ectopic pregnancy is a surgical emergency that due to the relation between the serum quantification of the of the beta subunit of human chorionic gonadotropin (β-HCG) and the ultrasonographic findings, there have been improvements to reach a precise diagnosis. However, there are very few reported cases in the literature where a broken ectopic pregnancy is described with negative serum results in β-HCG. We present a case report of a 25-year-old patient came to the evaluation for referring 12.2 weeks of menstrual delay, associated with transvaginal bleeding and data of peritoneal irritation, she had a negative β-HCG fraction (< 5 mIU/ml). A scan was performed ultrasound finding abundant free fluid in the cavity, without evidence of intrauterine pregnancy. Given the high suspicion of ectopic pregnancy, an exploratory laparotomy was performed, finding findings suggestive of a ruptured ectopic pregnancy, a salpingectomy was performed. Finally, in the postoperative study, a ruptured ectopic pregnancy was confirmed by histopathology. There are very few reported internationally were found a patient with clinical characteristics of broken ectopic pregnancy, with a β-HCG negative. It is important the scientific diffusion of this type of cases with the purpose of improving the diagnostic approaches and not underestimating importance to the clinical suspicion, despite presenting negative β-HCG results.

Beta-gonadotropina coriónica humana cualitativa, herramienta diagnóstica de rotura prematura de membranas ovulares en Honduras / Qualitative human beta chorionic gonadotropin for the diagnosis of premature rupture of membranes in Honduras

RESUMEN Objetivo : Analizar la beta gonadotropina coriónica humana (β-hCG) cualitativa como método diagnóstico de rotura prematura de membranas ovulares (RPM). Métodos: Estudio de casos y controles, prospectivo, con muestra no probabilística por conveniencia, de 90 mujeres entre 24 y 40 semanas de gestación divididas en dos grupos: grupo de estudio (45 pacientes con diagnóstico clínico de RPM) y grupo control (45 pacientes hospitalizadas sin RPM). Se realizó lavado o aspirado vaginal para determinar cualitativamente la β-hCG en kits comerciales de medición β-hCG con umbral de 25 mUI/mL, así también la prueba en papel de nitrazina. Resultados: La sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo para la prueba de β-hCG-25 fueron 77,8% (IC95%, 63,7 a 87,5), 82,2% (IC95%, 68,7 a 90,7), 81,4% y 78,7%, respectivamente. La precisión diagnóstica fue de 80,0% (0,6 índice kappa Landis & Koch) versus 75,6% para la pH-metría con nitrazina. Conclusiones: La prueba cualitativa de β-hCG mostró un valor diagnóstico representativo y puede corroborar el diagnóstico temprano de RPM, recomendándola por ser una prueba simple, rápida, accesible y de bajo costo.

ABSTRACT Objective : To analyze qualitative human beta chorionic gonadotropin (β-hCG) as a diagnostic method for premature rupture of membranes (PROM). Methods : Prospective case-control study, with a non-probabilistic sample by convenience, of 90 women between 24 and 40 weeks of gestation divided into two groups: study group (45 patients with clinical diagnosis of PROM) and control group (45 patients hospitalized without PROM). Vaginal lavage or aspirate was performed to qualitatively determine β-hCG in commercial β-hCG measurement kits with threshold of 25 mUI/mL as well as nitrazine paper test. Results : The sensitivity, specificity, positive predictive value, and negative predictive value for the β-hCG-25 test were 77.8% (95% CI, 63.7-87.5), 82.2% (95% CI, 68.7-90.7), 81.4%, and 78.7%, respectively. Diagnostic accuracy was 80.0% (0.6 Landis & Koch kappa index) versus 75.6% for nitrazine pH-metry. Conclusions : The qualitative β-hCG test showed a representative diagnostic value and can corroborate the early diagnosis of PROM, recommending it as a simple, rapid, accessible and low-cost test.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study

ABSTRACT Objective: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. Methods: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. Results: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. Conclusion: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Difficulty in Diagnosing of Renal Choriocarcinoma: Case Report / Dificuldade no diagnóstico do coriocarcinoma renal: relato de caso

ABSTRACT Choriocarcinoma is a rare highly malignant tumor. We report a case of 35-year-old woman, with a history of four months menstrual irregularity and human chorionic gonadotropin persistently positive that presented transvaginal ultrasound normal and the computed tomography scan of the chest showed three nodules and abdominal scan evinced a hypervascularized solid nodular lesion on left kidney. An ultrasound-guided biopsy of left kidney was performed with a pathologic diagnosis of renal choriocarcinoma. After chemotherapy the human chorionic gonadotropin was negative and the patient returned to normal menstrual cicles.

RESUMO O coriocarcinoma é um tumor altamente maligno raro. Relatamos um caso de mulher de 35 anos, com história de irregularidade menstrual de quatro meses e gonadotrofina coriônica humana persistentemente positiva que apresentava ultrassonografia transvaginal normal e a tomografia computadorizada de tórax com três nódulos e a abdominal evidenciava um nodular sólido hipervascularizado lesão no rim esquerdo. Uma biópsia guiada por ultrassom do rim esquerdo foi realizada com diagnóstico patológico de coriocarcinoma renal. Após a quimioterapia, a gonadotrofina coriônica humana foi negativa e a paciente retornou aos ciclos menstruais normais.

Spermatogenesis of combined HCG and HMG in patients with idiopathic hypogonadotropic hypogonadism and congenital combined pituitary hormone deficiency / 中华内分泌代谢杂志

Objective:To compare the spermatogenes response of human chorionic gonadotropin(HCG)combined with human menopausal gonadotropin(HMG)in patients with idiopathic hypogonadotropic hypogonadism(IHH)and congenital combined pituitary hormone deficiency(CCPHD), and to explore related factors.Methods:Clinical data of 90 IHH patients and 61 CCPHD patients from January, 2014 to November, 2018 were retrospectively analyzed. Spermatogenesis was compared between the two groups receiving combined gonadotropin therapy. The patients were then divided into two subgroups: spermatogenesis subgroup and nonspermatogenesis subgroup. Related factors of spermatogenesis after the combined gonadotropin therapy were investigated.Results:After the combined treatment of HCG/HMG for 3, 6, and 9 months, the patients with CCPHD revealed lower testicular sizes than those with IHH( P=0.004, 0.021 and 0.032, respectively). Compared with IHH patients, CCPHD patients had larger testicular volume increments( P<0.001), higher spermatogenesis rates( P=0.048), and shorter initial time for sperm appearance( P<0.001)after 24-month treatment. Multivariate logistic regression analysis showed that lower total cholesterol(TC)(IHH group: OR=5.508, 95% CI 1.110-27.326, P=0.037; CCPHD group: OR=4.068, 95% CI 1.077-15.371, P=0.039)was an independent risk factor of poorer spermatogenesis in patients with IHH and CCPHD. Conclusions:The patients with CCPHD demonstrate a better response to combined gonadotropin treatment than those with IHH. Lower TC is an independent risk factor for poor spermatogenesis of combined HCG/HMG therapy in patients with IHH or CCPHD.

Histopathological Changes that Occur on the Testicular and Penile Tissues Depending on the Treatment of Human Chorionic Gonadotropin: Rat Model

ABSTRACT Objective: To examine the histopathological effects of human chorionic gonadotropin (hCG) treatment on the penile and the testicular tissue in rat model. Methods: The rats of the hCG group (n = 8) were given daily subcutaneous injections of 50 IU of hCG for 15 days (Pregnyl, Organon). Rats of the control group (n = 8) received subcutaneous isotonic saline. All rats were sacrificed at the 1st month after hCG administration. After the received tissue samples were examined, germinal epithelial cell thickness, seminiferous tubule diameter, internal diameter of the tubules, the number of germ cell layers in the testicular tissue, and the diameters of penis, cavernous sinus lumen diameters and collagen tissue amount in the cavernous sinus surrounding were assessed in the sections prepared from the penis. Results: It was detected that there was a decrease in the testis weight, atrophy in the tubules, reduction in spermatogenesis, decrease in the mature spermatocytes, lower mean thickness and the number of cell layers of the germinal membrane in testicular tissue in the hCG group. It was found that the amount of collagen in the penile tissue was significantly higher in the hCG group and the diameters of cavernosal sinus lumens, and diameter of the penis were significantly lower in the hCG group. Conclusion: Human chorionic gonadotropin led to the deterioration in testicular histology and the histological changes in the penile tissue. The degradation in the testicular tissue and these changes formed in the penile tissue may affect the erectile tissue function.

Efficacy of laparoscopic uterine curettage combined with uterine artery embolization in the treatment of cesarean scar pregnancy after type Ⅲ cesarean delivery / 中国基层医药

Objective:To investigate the efficacy of laparoscopic uterine curettage combined with uterine artery embolization in the treatment of cesarean scar pregnancy (CSP) after type Ⅲ cesarean delivery.Methods:Sixty patients with type Ⅲ CSP who received treatment in Jinxiang Hospital Affiliated to Jining Medical University from January 2017 to October 2019 were included in this study. They were randomly assigned to undergo either laparoscopic uterine curettage alone (control group, n = 30) or laparoscopic uterine curettage combined with uterine artery embolization (observation group, n = 30). The amount of intraoperative blood loss, length of hospital stay, surgical cure rate, time to beta human chorionic gonadotropin (β-HCG) value returning to normal level, and the incidence of postoperative complications were compared. Results:The amount of intraoperative blood loss in the observation group was significantly less than that in the control group [(42.36 ± 15.03) mL vs. (119.52 ± 21.84) mL, t = 15.941, P < 0.05]. Length of hospital stay [(6.51 ± 2.21) days vs. (19.25 ± 3.43) days] and the time to β-HCG value returning to normal level [(16.25 ± 5.02) days vs. (28.02 ± 9.38) days] in the observation group were significantly shorter than those in the control group ( t = 17.102, 6.060, both P < 0.05). There was no significant difference in surgical cure rate between the observation and control groups [96.67% (29/30) vs. 90.00% (27/30), χ2 = 0.268, P > 0.05]. There were no significant differences in the incidence of postoperative fever [63.33% (19/30) vs. 56.67% (17/30)], pain [56.67% (17/30) vs. 46.67% (14/30)], infection [6.67% (2/30) vs. 10.00% (3/30)] and vaginal bleeding [6.67% (2/30) vs. 13.33% (4/30)] between the observation and control groups ( χ2 = 0.278, 0.601, 0.000, 0.185, all P > 0.05). Conclusion:Laparoscopic uterine curettage combined with uterine artery embolization for the treatment of type Ⅲ CSP is superior to laparoscopic uterine curettage alone in terms of intraoperative blood loss, hospital stay, surgical cure rate, time to β-HCG value returning to normal level and safety. Therefore, the combined method is worthy of clinical application.

Beta-human chorionic Gonadotropin levels as early predictor for progression to Gestational Trophoblastic Neoplasia after molar pregnancy evacuation at a Philippine tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#This study aimed to determine if the beta-human chorionic gonadotropin (hCG) levels during the first 5 weeks after a molar evacuation predict progression to gestational trophoblastic neoplasia (GTN).@*Materials and Methods@#This was a retrospective cohort study of complete mole cases managed at a Philippine tertiary hospital from January 2009 to December 2018. Extracted data were analyzed using applicable statistical tools. The level of significance was set at a P < 0.05 using two-tailed comparisons. @*Results@#One hundred and fifty-five complete patient records were available for review. Disease progression in 15.48% of cases while regression in 84.52% were noted. Uterine size was larger in those who eventually had postmolar GTN (t: −3.12, df: 32.64, P: 0.01). Analysis of the receiver operating characteristic curve showed that optimum cut-off levels for predicting GTN at 1, 3, and 5 weeks after evacuation were 4,152 mIU/ml (sensitivity: 50%, specificity: 94.7%, area under the curve [AUC]: 0.75), 804 mIU/ml (sensitivity: 62.5, specificity: 96.9%, AUC: 0.94), and 541 mIU/ml (70.8%, specificity: 97.7%, AUC: 0.96), respectively. @*Conclusion@#The level of hCG within the first 5 weeks after molar pregnancy evacuation is predictive of progression to GTN.

Testicular germ cell tumors type 2 have high RNA expression of / 亚洲男科学杂志(英文版)

This study analyzed RNA expression of genes for three serum tumor markers, alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH), in patients with testicular germ cell tumors (TGCT) type 2. The gene AFP encodes AFP, the gene for chorionic gonadotropin beta polypeptide 5 (CGB5) encodes a major part of the specific beta subunit of hCG, and the genes for LDH subunit A (LDHA), LDH subunit B (LDHB), and LDH subunit C (LDHC) encode three different subunits of LDH. LDHB encodes the LDHB subunit present as a tetramer in LDH isoenzyme 1 (LDH-1). We examined three datasets with 203 samples of normal testis tissue (NT) and TGCT type 2. Yolk sac tumor (YST) expressed RNA of AFP fourteen thousand times higher than seminoma (SE), embryonal carcinoma (EC), and teratoma (TER) combined (P = 0.00015). In the second microarray, choriocarcinoma (CC) expressed RNA of CGB5 ten times higher than other histologic types of TGCT combined. EC expressed RNA of LDHB twice higher than SE, YST and TER combined (P = 0.000041). EC expressed RNA of LDHB higher than that YST expressed RNA of AFP and that CC expressed RNA of CGB5. In conclusion, TGCT type 2 expressed RNA of LDHB markedly higher than the RNA of 23 other candidate genes for TGCT type 2.

A rare case report of recurrent ectopic pregnancy

This case presenting a 30-year-old lady, a case of G4A1E2 who presented with history of 1 month of amenorrhoea, followed by bleeding per vaginum 1 week back for 3 days. Presented to hospital with spotting PV and pain abdomen for 2 days. UPT done at home was positive. USG revealed right ovarian complex haemorrhagic cyst and left adnexal ectopic pregnancy near left ovarian fimbriae. Conservative management by Methotrexate and Folinic acid regimen was tried but as there were no signs of resolution on serial ultrasonography reports and serial human chorionic gonadotropin (hCG) levels did not fall as expected, hence decision of laparoscopy/laparotomy was made and salpingectomy was done. Later patient was followed up with serial hCG levels.