Trophoblastic Disease Research Articles

Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

The Effects of Induction Chemotherapy in the Management of Ultra High-Risk Gestational Trophoblastic Neoplasia.

This study aimed to determine the clinical outcomes of ultra high-risk gestational trophoblastic neoplasia (GTN) patients managed with and without induction chemotherapy in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital. Clinical and demographic data were collected retrospectively from ultra high-risk GTN patients admitted in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital from January 2015 to December 2021. Rate of remission and early death of those who received induction chemotherapy were compared to those who did not. A total of 21 patients with ultra high-risk GTN were included in the study, nine of whom underwent induction chemotherapy while 12 had no induction chemotherapy and was given the standard EMACO regimen. There was no significant difference in the rate of early death as well as the rate and time to achieve remission between those who received induction chemotherapy compared to those who were immediately started on EMACO. A firm conclusion cannot be drawn from the results considering the small population included in the study. Further studies with larger sample size and prospective study design are recommended.

Clinical case of arteriovenous malformation of the uterus after trophoblastic disease

Clinical case of arteriovenous malformation of the uterus after trophoblastic disease

Assessment of risk factors associated with post-molar gestational trophoblastic neoplasia: a retrospective cohort

Assessment of risk factors associated with post-molar gestational trophoblastic neoplasia: a retrospective cohort

Choriocarcinoma presenting as late postpartum hemorrhage in a 21-year-old primipara

INTRODUCTION: Obstetrical hemorrhage remains to be one of the most common causes of maternal morbidity and mortality. Postpartum hemorrhage occurs after delivery and is usually secondary to uterine atony, genital tract lacerations, and retained placental fragments. CASE: A case of a 21-year old, primipara, presented with profuse vaginal bleeding and hemoptysis at 3 weeks' postpartum. A clinical diagnosis of gestational trophoblastic neoplasia was established after an elevated serum beta human chorionic gonadotropin was obtained and an intrauterine mass was seen on ultrasonography, including metastasis to the lungs and liver seen through imaging studies. DISCUSSION: Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin (EMACO) is the mainstay treatment for Stage IV disease. However, complications such as hemorrhage and tumor rupture are best managed surgically. Although rare, a diagnosis of choriocarcinoma should be considered in patients with persistent bleeding after a normal pregnancy to institute proper management and avoid associated complications of tumor progression.

Molar Pregnancy with a Coexistent Fetus following Assisted Reproductive Techniques: A Review of Literature of the Clinical Course and Sequelae

Abstract The clinical course and sequelae of molar pregnancy pose several diagnostic and management challenges, especially conceiving after assisted reproductive technology. A review of the literature was conducted on molar pregnancy with a coexistent fetus following assisted reproductive techniques, its clinical course, and sequelae. The literature review was conducted using search terms “coexistent fetus,” “hydatidiform mole,” “twin,” “assisted conception” AND “persistent gestational trophoblastic disease (PGTD)” OR “chemotherapy” in PubMed. A literature search identified 26 reported cases conceived following assisted conception. Management guidelines for hydatidiform mole with live fetuses are very vague and do not give specificity due to the fact that it is often associated with complications and bad obstetric outcomes. It also requires continuous monitoring and follow-up in a tertiary care center anticipating disease progression to postnatal PGTD. To assess the risk of continuation of pregnancy, multicentric studies with larger sample sizes are required to have a valid finding.

Role of continuing regular follow-up of serial B-human chorionic gonadotropin measurements with health education following initial surgical management of complete molar pregnancy cases

Objective: Our goal to confirm complete cure, early detection of persistent gestational trophoblastic disease and more effective and less complex treatment. Methods: Fifty-one patients from 12,960 were admitted to the Department of Obstetrics and Gynecology at Tobruk Medical Center between August 2018 and July 2021 with complete molar pregnancy, the diagnosis was confirmed with histopathology after initial surgical management. Following identification of these patients, due to lack of registration centers, the patient's telephone was required to complete the data for continuing regular follow-ups over a period of time these patients were evaluated prospectively according to their age, number of deliveries, history of normal and abnormal pregnancy, the quantity of beta-human chorionic gonadotropin (B-HCG) at the time of diagnosis and follow-up and treatment type. Persistent gestational trophoblast disease was diagnosed on the basis of a rise of B-HCG after initial evacuation, and just one patient in our study diagnosed with invasive mole and underwent second evacuation and none of these patients developed choriocarcinoma during the follow-up period. Analysis was conducted by using the social package of statistical science (SPSS) version 25 software. Results: 51 patients (0.39%) were diagnosed with complete molar pregnancy (CMP), the mean age was 31.90 (8.169) years range (17-47 years). Among 51 patients with CMP over three years, seventeen patients (33.3%) were diagnosed with persistent gestational trophoblast disease (PGTD), the incidence is about 1.3 per 1000 per deliveries, thirty-four patients (66.7%) reached spontaneous remission of molar gestation in a median time of 61 days and had a total follow-up time of 24 months. Conclusion: Follow-up women with complete molar pregnancy especially after initial management is challenging task as the incidence of molar pregnancy increasing and exposed to the risk of developing persistent gestational trophoblastic disease, and there are no specialist centres for documentation and surveillance programme. And due to wide geographical area in Libya and difficulty in the follow-up patients with molar pregnancies, especially after initial treatment has been performed. Therefore, we must create multiple centers throughout the country to cover all cases as much as possible and the communication between the patients and centers via internet, to ensure early detection of pregnancy complications.

A case of epithelioid trophoblastic tumor (ETT) diagnosed by hysteroscopic biopsy

A case of epithelioid trophoblastic tumor (ETT) diagnosed by hysteroscopic biopsy

Presentation Invasive Mole After Normal Pregnancy: A Very Rare Case Report

Gestational trophoblastic neoplasia (GTN) is a rare neoplasm and is a spectrum of proliferative disorders of placenta. Invasive mole is a subtype of GTN that almost always arises after molar pregnancy. This report presents a 35-year-old woman with an atypical presentation of invasive mole after a normal pregnancy. The patient presented with a complaint of vaginal bleeding after normal vaginal delivery. Invasive mole was diagnosed based on findings of imaging and elevated beta human chorionic gonadotropin (ß-hCG) levels. Hysterectomy was finally decided upon due to severe vaginal bleeding and the patient’s request. Although GTN occurs after normal delivery, the patient recovered without receiving chemotherapy. It is important to consider all subtypes of GTN as a differential diagnosis of patients with abnormal postpartum bleeding and elevated ß-hCG levels even after a normal pregnancy.

Fertility Preservation Approach in a Case of Perforating Gestational Trophoblastic Neoplasia

Background: Gestational trophoblastic neoplasia following spontaneous abortion is rare and in majority cases the approach is hysterectomy followed by chemotherapy. Case: We present case of a 22-year-old woman who presented with complaints of vaginal bleeding for 2 months; pain abdomen for 3-4 days. On reviewing history, patient was one and a half months pregnant and had spontaneous abortion for which she underwent twice dilatation and curettage and once laparotomy in outside hospital. Patient continued to bleed &amp; MRI pelvis was done which revealed arteriovenous malformation and was thereafter referred to our hospital. On presentation her vitals were stable with pallor positive. On per-abdominal examination there was generalized tenderness and mild bleeding on per speculum examination. Her serum beta hCG at the time of admission was 98,156IU/L. Ultrasound pelvis revealed a highly vascular heterogenous hypoechoic mass showing significant internal and peripheral vascularity. We decided for uterine artery embolization owing to highly vascular GTN, young age and no live issues with the aim of uterine preservation. This was followed by chemotherapy with serial beta hcg monitoring. She is in her 14th month of follow up with resolution of her complaints. Conclusion: The aim behind presenting this case is its rarity of presentation as well as management to increase awareness among treating gynecologists. Importance of multi-disciplinary approach should not be undermined in challenging cases.

Management of gestational trophoblastic diseases

No abstract available

Unveiling hemorrhagic shock from partial hydatidiform mole: A case study at Beja maternity ward

Introduction: Partial hydatidiform mole (PHM) is one of the gestational trophoblastic diseases characterized by cystic transformation of chorionic villi, retaining recognizable placental morphology, and an amniotic cavity with a fetus. Its incidence is approximately 3 per 1000 pregnancies. Symptomatology is marked by the occurrence of metrorrhagia following amenorrhea, most commonly in the first trimester and rarely in the second trimester. Case Report: We present a case of threatened premature delivery complicated by hemorrhagic shock, revealing a partial hydatidiform mole at 23 weeks of gestation. The diagnosis of PHM in the context of such clinical presentation underscores the importance of recognizing this rare entity early in pregnancy to facilitate appropriate management and optimize maternal and fetal outcomes. Conclusion: The provided text has already been divided into the Introduction, Case Report, and Conclusion sections as outlined above.

Circ_0001861 facilitates trophoblast cell proliferation, migration, invasion and epithelial-mesenchymal transition via the miR-296-5p/forkhead box protein 1 pathway in preeclampsia.

Preeclampsia (PE) is one of the leading causes of maternal mortality and placental trophoblastic disorders. Recent studies reported that circular RNAs (circRNAs) were involved in PE pathogenesis. However, the role of circ_0001861 in PE progression is largely unknown. The RNA expression of circ_0001861, forkhead box protein 1 (FOXP1) and microRNA-296-5p (miR-296-5p) was detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Western blot assay was performed to examine the protein levels of FOXP1 and epithelial-mesenchymal transition (EMT) markers. Cell viability, proliferation, migration and invasion were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. Luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation (RIP) assay were conducted to explore the interaction between miR-296-5p and circ_0001861 or FOXP1. Circ_0001861 and FOXP1 were downregulated but miR-296-5p was upregulated in PE placenta. Upregulation of circ_0001861 facilitated trophoblast cell proliferation, migration, invasion and EMT. Mechanistically, circ_0001861 sponged miR-296-5p to elevate FOXP1 expression, thus promoting trophoblast cell progression. The circ_0001861/miR-296-5p/FOXP1 axis plays a critical role in trophoblast cell proliferation, migration, invasion and EMT, which may provide a novel insight into developing potential therapeutic targets for PE.

Hybridization chain reaction assisted multicolor immunosensor for sensitively detection of human chorionic gonadotropin

The level of human chorionic gonadotropin (HCG) is an important indicator for early pregnancy, pregnancy-related diseases trophoblastic diseases and even cancer diagnosis. Therefore, sensitive detection of HCG has crucial significance in clinical, especially in gynaecology and obstetrics. Herein, a hybridization chain reaction (HCR) assisted multicolor immunosensor have been developed for HCG analysis. The proposed method introduced HCR after the immunoreaction between antibody and HCG protein, and produced long double strand DNA (dsDNA) that contain biotin sites. The streptavidin-horseradish peroxidase was linked on the dsDNA by the interaction between biotin and streptavidin, and can further mediated gold nanobipyramids (Au NBPs) etching. The localized surface plasmon resonance absorption peaks of Au NBPs blue shift and accompanied a vivid color change after etching effect. Based on this color change, HCG could be qualitative and semi-quantitative detected. Because of the introduction of HCR and enzyme amplification technique, the proposed method exhibited high sensitivity with a linear range of 0.1–2000 pg/mL and limit of detection (LOD) of 0.1 pg/mL. Finally, the proposed immunosensor was used to detect clinical serum samples. The results show there are no significant differences between clinical results and the test results by this method, indicating the practicability of the proposed method.

Management of Entero-Uterine Fistula Which Developed Following Trans-Arterial Embolization of Arteriovenous Malformation Associated with Gestational Trophoblastic Neoplasia

Management of Entero-Uterine Fistula Which Developed Following Trans-Arterial Embolization of Arteriovenous Malformation Associated with Gestational Trophoblastic Neoplasia

METHOTREXATE-INDUCED ORAL ERYTHEMA MULTIFORME

Objective: To discuss the management of oral erythema multiforme (EM) due to methotrexate (MTX) in gestational trophoblastic tumor patients.&#x0D; Methods: A 28-year-old woman was referred to the Oral Medicine Clinic with complaints of pain throughout the oral cavity accompanied by blackish encrustation on the upper and lower lip for 5 d. She previously underwent the first cycle of chemotherapy using MTX for the treatment of a gestational trophoblastic tumor. Extraoral, multiple diffuse blackish patches on the face and haemorrhagic crusts on the lips with painful erosions. Intraoral, multiple erosive and ulcerative lesions on the labial and buccal mucosa.&#x0D; Results: Management involved topical 0.025% hyaluronic acid mouthwash for erosion and ulceration, compressed 0.9% NaCl for crusted lesions on the lips, and petroleum jelly for the non-crusted lesions on the lips. Complete healing of oral and lip lesions was achieved within 10 d.&#x0D; Conclusion: Pharmacological management should be tailored to each patient with careful consideration of treatment risk or benefit. In our case, the use of non-steroidal anti-inflammatory topical agents was considered successful in treating oral EM.

PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia

ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management. MethodsUsing training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset. ResultsThree streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms. ConclusionsOur streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended.

Hydatidiform Mole-Between Chromosomal Abnormality, Uniparental Disomy and Monogenic Variants: A Narrative Review.

A hydatidiform mole (HM) or molar pregnancy is the most common benign form of gestational trophoblastic disease characterized by a proliferation of the trophoblastic epithelium and villous edema. Hydatidiform moles are classified into two forms: complete and partial hydatidiform moles. These two types of HM present morphologic, histopathologic and cytogenetic differences. Usually, hydatidiform moles are a unique event, but some women present a recurrent form of complete hydatidiform moles that can be sporadic or familial. The appearance of hydatidiform moles is correlated with some genetic events (like uniparental disomy, triploidy or diandry) specific to meiosis and is the first step of embryo development. The familial forms are determined by variants in some genes, with NLRP7 and KHDC3L being the most important ones. The identification of different types of hydatidiform moles and their subsequent mechanisms is important to calculate the recurrence risk and estimate the method of progression to a malign form. This review synthesizes the heterogeneous mechanisms and their implications in genetic counseling.

Atypical presentation of hyperthyroidism complicated complete hydatidiform mole in a 24-year-old female: a case report

Introduction and importance: Molar pregnancy is the most common type of gestational trophoblastic disease. It manifests as vaginal bleeding, accompanied by high levels of β-human chorionic gonadotropin (β-HCG). This case aims to highlight the importance of considering gestational trophoblastic disease as a potential diagnosis and its serious complications. Case presentation: A 24-year-old female presented with vomiting, nausea, and no complaint of vaginal bleeding. Laboratory tests indicated hyperthyroidism as a complication requiring challenging preoperative prophylactic management. Initially, the patient underwent suction and curettage, but a total hysterectomy had to be performed later. The histological study concluded with the diagnosis of a complete hydatidiform mole. Post-surgery follow-up evaluations revealed high blood pressure values, and the patient was appointed for further cardiology assessment. Discussion and conclusion: Although uncommon, complications of a molar pregnancy include anaemia, severe cardiac distress, and hyperthyroidism. Trophoblastic Hyperthyroidism is a result of extremely high levels of β-HCG levels due to molecular cross-reactivity. History, clinical examination, and ultrasound, in addition to measuring β-HCG levels, could all help in diagnosing a molar pregnancy, but the definitive diagnosis is based on histopathology and a karyotype study. Management procedures include dilation, suction and curettage, and hysterectomy. The treatment depends on the patient’s age, desire for future pregnancies, and risk of developing gestational trophoblastic neoplasia. A follow-up with serial β-HCG measurement is recommended to monitor possible complications. Attaining and maintaining euthyroidism is a life-saving procedure before molar pregnancy surgery. Methimazole, Propranolol, Lugol’s iodine, and hydrocortisone can all be used in the prophylactic management of the thyroid storm.

The evaluation of maternal serum glycodelin level as a marker for the presence and severity of preeclampsia

Abstract Background: Preeclampsia (PE) is a common multisystemic disorder of pregnancy. Glycodelin is a glycoprotein belongs to the lipocalin superfamily. It acts as a regulator of immunosuppression activity, fertilization, implantation, and placentation. Objectives: To analyze serum glycodelin levels in PE and evaluate whether it correlates with the severity of the disease. Materials and Methods: A prospective case–control study included 60 women diagnosed with PE (subdivided into 30 pregnant women with mild PE and 30 pregnant women with severe PE) and 30 healthy normotensive pregnant women. Patient with multiple pregnancies, gestational trophoblastic diseases, in active labor, a history of medical diseases, or taking treatment were excluded from the study. Blood samples were taken for biochemical study; serum glycodelin levels were measured using an enzyme-linked immunosorbent assay. Results: Patients with PE had significantly higher mean glycodelin levels as compared to the normal group. The glycodelin level ≥37.9 ng/mL had 96.70% sensitivity, 100% specificity, and 98% accuracy for the prediction of PE. The mean glycodelin was significantly higher in severe PE (102.3 ± 51.3) as compared to mild PE (45.2 ± 7.3) in pregnant women (P &lt; 0.001). The glycodelin level ≥50.1 ng/mL had 86.7% sensitivity, 80% specificity, and 85% accuracy for the prediction of severe PE. Conclusions: Glycodelin is an appropriate marker for the diagnosis of PE and the categorization of disease according to severity.