Search Results (28)

Background and Objectives: This study aimed to evaluate obstetric, neonatal, and oncologic outcomes of pregnancies complicated by a hydatidiform mole coexisting with a live fetus (HMCF) carried beyond viability, and to assess the impact of delivery mode on outcomes. Materials and Methods: A systematic review and individual participant data meta-analysis included HMCF cases progressing beyond 23 weeks. Obstetric and neonatal outcomes, delivery patterns, and oncologic risks were analyzed. Results: Among 118 pregnancies complicated by HMFC (124 newborns), most were complete moles (87%). Median delivery occurred at 31.6 weeks, with over half before 32 weeks. Common complications included vaginal bleeding (59%), preeclampsia (30%), and hyperthyroidism (18%). Cesarean delivery was performed in 79% of cases, often for mole-related factors, but was not associated with reduced maternal or oncologic risk. Neonatal deaths occurred exclusively in infants delivered ≤32 weeks, highlighting extreme prematurity as the key determinant of survival. Severe preeclampsia was strongly linked to earlier delivery. Conclusion: With close monitoring, continuation of HMCF pregnancies is possible. Neonatal mortality is mainly driven by prematurity, which appears to be an indirect consequence of HMFC through the development of mola-associated complications. Cesarean section does not appear to improve maternal and oncologic outcomes. Vaginal delivery can be considered when no standard contraindications exist. Full article

Objectives: To evaluate the potential associations of the type of complete hydatidiform mole (CHM) initial treatment (hysterectomy or uterine evacuation) with GTN development, need for chemotherapy, and treatment outcome in women aged ≥ 40 years. Methods: This multicentric retrospective cohort study included women ≥ 40 years with CHM, initially treated between 1990 and 2018, at four different centers. Data collected included patient demographics and clinical characteristics. The outcome variables were post-CHM GTN development, need for chemotherapy for hCG normalization, surgical complications, and time to remission. Univariate and multivariate analyses were performed using chi-square, Mann–Whitney, Fisher’s exact tests, and Poisson regression. Results: 275 women with CHM aged ≥ 40 years were included in the analysis. Median patient age was significantly higher among hysterectomy patients (47 × 44 years, p = 0.01). Multivariate analysis showed that compared with uterine evacuation (244/275, 89%), hysterectomy (31/275, 11%) was associated with an 83% lower risk of GTN [RR = 0.17 95% CI = (0.04–0.71); p = 0.015] and a 92% lower risk of requiring chemotherapy [RR: 0.08 (0.01–0.64), p = 0.016]. Median time to hCG normalization did not statistically differ between treatments. No significant differences were observed between hysterectomy and uterine evacuation in terms of FIGO staging (p = 0.221) or prognostic risk score (p = 0.576). Resistance to first-line chemotherapy (17/72; 23.6%) and relapse (3/72; 4.1%) were observed only in patients undergoing initial uterine evacuation. Hysterectomy complications occurred in 45.1% (14) of the patients. Conclusions: CHM initial treatment with hysterectomy was associated with a lower risk for GTN occurrence and need for chemotherapy in women aged 40 years or older. However, shared decision-making about surgery should be tailored to each patient and their risk factors and preferences. Further, larger controlled studies are required to support our findings. Full article

Background/objectives: Gestational trophoblastic diseases (GTDs) are rare premalignant and malignant conditions characterized by abnormal proliferation of trophoblastic tissue. They are often asymptomatic but may present with vaginal bleeding. GTDs include hydatidiform moles and gestational trophoblastic neoplasms (GTNs). Current research aims to improve diagnostic tools and treatment strategies to reduce cancer risk and improve survival. Increasing attention is being paid to immunotherapy and treatment personalization, with the goal of minimizing long-term side effects and enhancing quality of life. Less toxic therapies are ideal for low-risk patients to reduce drug-related toxicity. Materials and Methods: A narrative review was conducted to analyze studies from the last twenty years on the diagnosis, staging, and treatment of GTDs. Sources included PubMed, Scopus, and Cochrane Library, using keywords such as “trophoblastic disease,” “hydatidiform mole,” and “gestational trophoblastic neoplasia.” Results: In recent years, the clinical management of gestational trophoblastic disease (GTD) has made significant progress through diagnostic, prognostic, and therapeutic innovations. More sensitive imaging techniques and serial monitoring of serum β-hCG now allow early diagnosis of hydatidiform mole and gestational trophoblastic neoplasia (GTN), reducing the risk of complications and metastasis. Conclusions: In the last decade, GTD management has improved significantly, with better diagnostic techniques, standardized staging, and more effective treatments. However, challenges persist, including relapse management, long-term monitoring, and psychological support. Early diagnosis is key, with ultrasound being essential for detecting abnormalities in the first weeks of pregnancy. Staging follows FIGO and WHO criteria, considering hCG levels and metastasis. This review highlights recent advances in diagnostic tools, emerging therapies—including immunotherapy—and the need for personalized, less toxic treatment approaches to improve patient outcomes. Full article

Objectives: The purpose of this retrospective cohort study was to ascertain the risk of abortion, ectopic pregnancy and hydatidiform mole development in women with polycystic ovary syndrome (PCOS) using data from Korea’s National Health Insurance Service. Method: The women aged 20–49 years who were diagnosed with PCOS between 1 January 2012 and 31 December 2020 were enrolled. The control group (non-PCOS group) was composed of women aged 20–49 years who visited medical institutions for health examinations during the same period. Women diagnosed with any cancer were excluded from both groups. Logistic regression analysis was used to evaluate the risks of abortion, ectopic pregnancy and hydatidiform mole in PCOS in the presence of certain pregnancy-related confounding factors. Results: A total of 724,307 women were extracted, 169,998 women without PCOS and 44,714 women with PCOS were enrolled in the study. The PCOS group had a higher incidence of GDM and endometriosis. Abortions, ectopic pregnancies and hydatidiform moles were higher in the PCOS group than in the control group (abortion: 14.7% vs. 7.3%, p < 0.001; ectopic pregnancy: 3.3% vs. 1.1%, p < 0.001; hydatidiform mole: 0.2% vs. 0.1%, p < 0.001). After adjusted logistic regression, PCOS was found to be a risk factor for abortion (RR = 1.473, 95% CI = 1.424–1.524; p < 0.001) and ectopic pregnancy (RR = 1.845, 95% CI = 1.716–1.984, p < 0.001) but not hydatidiform mole (RR = 1.225, 95% CI = 0.927–1.62, p = 0.154). Conclusions: A history of PCOS itself might increase the risk of abortion and ectopic pregnancy. These findings could be useful in prenatal counseling and the management of patients with PCOS-associated pregnancies. Full article

Hydatidiform mole is a trophoblastic disorder resulting from abnormal fertilization. Diagnosis is established through a combination of clinical findings, elevated serum human chorionic gonadotropin (hCG) levels, and characteristic features on transvaginal ultrasound. Timely and accurate diagnosis is essential for initiating prompt treatment and preventing medical complications. Uterine evacuation, preferably via vacuum aspiration, is the treatment of choice due to its high efficacy and safety profile. Adjunctive techniques, such as hysteroscopy and intraoperative ultrasonography, enhance the safety and effectiveness of uterine evacuation and should be available to patients, especially at specialized referral centers equipped to manage this diagnosis. In selected cases, particularly in women with fulfilled reproductive goals or those at a high risk of developing post-molar gestational trophoblastic neoplasia (GTN), total abdominal hysterectomy is appropriate. Postoperative follow-up with serial measurements of hCG is essential for monitoring remission and for the early detection of post-molar GTN, which develops in approximately 20% of cases of complete molar pregnancies and 1–4% of partial molar pregnancies. This article provides a comprehensive review of the diagnosis of hydatidiform mole and the surgical techniques employed in the treatment of this condition, emphasizing individualized care and the use of appropriate surgical strategies to treat complications associated with this trophoblastic disease. Full article

Background and Clinical Significance: Ovarian ectopic pregnancy (OEP) is a rare occurrence, and molar degeneration is even more exceptional. Differential diagnosis between a partial and complete hydatidiform mole is paramount as the complete type carries a higher risk of post-molar gestational trophoblastic neoplasia. Herein, we describe a case of a partial mole in an OEP (OPHM) with thorough investigations. Case Presentation: A 39-year-old woman presented at 6 weeks of amenorrhea with abdominal pain and vaginal bleeding. Ultrasound showed no intrauterine pregnancy, but an ovarian cyst suspicious for OEP. The patient underwent surgical removal of the cyst. Histological diagnosis was suspicious for OPHM with only one abnormal villous. Immunohistochemistry for p57^kip2 and fluorescent in situ hybridization (FISH) were not conclusive. STR-based (Short Tandem Repeat) molecular technique demonstrated the chromosomal asset of 69,XXX, confirming the diagnosis of OPHM. The patient was fully monitored for 1 year with periodic measurements of beta-hCG levels. After that period, the patient was in good health and disease-free. Conclusions: Histologically, ancillary techniques might not be sufficient to confirm the diagnosis of a hydatidiform mole, especially if the tissue available is scarce. In this case, STR has been demonstrated an effective tool in defining the chromosomal asset, even in paraffin-embedded samples. Full article

Molar pregnancy (MP) is a gestational disorder resulting from abnormal fertilization, leading to atypical trophoblastic proliferation and the formation of a complete or partial hydatidiform mole. This condition represents the most common form of gestational trophoblastic disease (GTD) and carries a significant risk of progression to gestational trophoblastic neoplasia (GTN). Although rare in high-income countries, MP remains up to ten times more prevalent in low-income and developing countries, contributing to preventable maternal morbidity and mortality. This narrative review provides an updated, practical overview of the clinical presentation, diagnosis, treatment, and follow-up of MP. A key focus is the challenge of early diagnosis, particularly given the increasing frequency of first-trimester detection, where classical histopathological criteria may be subtle, leading to diagnostic errors. The review innovates by integrating advanced diagnostic methods—combining histopathology, immunohistochemistry using p57Kip2, Ki-67, and p53 markers, along with cytogenetic analysis—to improve diagnostic accuracy in early gestation. The central role of referral centers is also emphasized, not only in facilitating timely treatment and access to chemotherapy, but also in implementing standardized post-molar follow-up protocols that reduce progression to GTN and maternal mortality. By focusing on both advanced diagnostic strategies and the organization of care through referral centers, this review offers a comprehensive, practice-oriented perspective to optimize patient outcomes in GTD and address persistent care gaps in high-burden regions. Full article

Background/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by increased trophoblast proliferation, rarely complicated by hyperthyroidism. Methods: Our systematic literature review (PRISMA guidelines; PubMed, Web of Science, and Scopus databases) searched for histologically confirmed cases of GTN associated with clinical or subclinical hyperthyroidism. We described the clinical–pathologic features and the pathways of hyperthyroidism in GTD. Results: We identified just 32 choriocarcinomas and one PSTT; other non-histologically confirmed cases could have been identified, as some patients received a clinical diagnosis based on serum human chorionic gonadotropin (hCG) levels and imagining data and were treated accordingly. As regards choriocarcinomas, patients’ age range was 15–45 (mean 27) years. Metastases involved the lungs (53%), brain (25%), and liver (19%) (less frequently, the kidneys, spleen, ovaries, vagina, pelvis/abdomen, or thyroid). The time to recurrence range was 1–36 (mean 12) months. On follow-up, 10 patients (32%) were alive with disease and 6 (19%) showed no evidence of disease, while most of the women (15 cases, 48%) died of disease. The hCG level range was 10,000–3,058,000,000 (mean 128,957,613) IU/L. At least some symptoms and/or signs of hyperthyroidism were evident with variable intensity in most cases and significantly improved within 2–3 weeks after treatment. Conclusions: Increased trophoblast proliferation could stimulate thyroid function via increasing the half-life of thyroxine-binding globulin. Secondly, increased hCG demonstrates cross-reactivity with the thyroid-stimulating hormone due to similar α-subunits. Moreover, basic isoforms of hCG may facilitate thyrotropic activity. Full article

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null–homozygote (N–H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles. Sensitivity was approximately 20% for in-house results from BB and CC and around 5% for AA. Dynamic Read Analysis for GENomics (DRAGEN) analyses identified 1.34 to 1.71 times more variants, detecting over 96% of in-house variants, with sensitivity for common variants increasing to 5%. In-house FP errors varied significantly among companies (up to 13.97 times), while DRAGEN minimized this variation. Despite DRAGEN showing higher FP errors for BB and CC, the increased sensitivity highlights the importance of effective bioinformatic conditions. We also assessed the potential effects of target enrichment and proposed optimal cutoff values for the read depth and variant allele fraction in WES. Optimizing bioinformatic analysis based on sensitivity and specificity from reference standards can enhance variant detection and improve the clinical utility of WES. Full article

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies. Full article

Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty oocyte (complete hydatidiform mole (CHM); mostly 46,XX) or two sperms fertilize one oocyte (partial hydatidiform mole (PHM); mostly 69,XXY). Notably, recurrent occurrences are associated with abnormal genomic imprinting of maternal effect genes such as NLRP7 (chromosome 19q13.4) and KHDC3L (chromosome 6q1). Ongoing efforts to enhance identification methods have led to the identification of growth-specific markers, including p57 (cyclin-dependent kinase inhibitor 1C; CDKN1C), which shows intact nuclear expression in the villous cytotrophoblast and villous stromal cells in PHMs and loss of expression in CHMs. Treatment of hydatidiform moles includes dilation and curettage for uterine evacuation of the molar pregnancy followed by surveillance of human chorionic gonadotropin (HCG) levels to confirm disease resolution and rule out the development of any gestational trophoblastic neoplasia. In this review, we provide a synopsis of the existing literature on hydatidiform moles, their diagnosis, histopathologic features, and management. Full article

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. Full article

Background and Objectives: Gestational trophoblastic disease (GTD) is a group of pregnancy-related malignant and premalignant diseases. The aim of this study was to assess the prognostic value of clinical characteristics to predict treatment outcomes in women with GTD. Materials and Methods: In this retrospective study, 34 patients treated for GTD at the Division of Gynaecology and Perinatology, University Medical Centre Maribor, between 2008 and 2022 were identified. Clinical and pathological characteristics were obtained by analysing patient data records. Results: Within the cohort of 34 patients with GTD, 29 patients (85.3%) had a partial hydatidiform mole (HM) and five patients545 (14.7%) had a complete HM. Two patients with a complete HM developed a postmolar gestational trophoblastic neoplasia (GTN), which represents 5.8% of all cases. Conclusions: GTD is a rare disease that is frequently asymptomatic. The subsequent consequences of GTD, which can lead to malignant transformation, as well life-threatening disease complications, warrant training for early recognition of HMs and timely treatment and surveillance. Full article

Twin pregnancy with a complete hydatidiform mole and coexisting fetus (CHMCF) is an exceedingly rare condition with an incidence of about 1 in 20,000–100,000 pregnancies. It can be detected by prenatal ultrasonography and an elevated maternal serum beta-human chorionic gonadotropin (BhCG) level. Herein, the author reports a case of CHMCF which was incidentally diagnosed through pathologic examination without preoperative knowledge. The 41-year-old woman, transferred due to preterm labor, delivered a female baby by cesarean section at 28 + 5 weeks of gestation. Clinically, the surgeon suspected placenta accreta on the surgical field, and the placental specimen was sent to the pathology department. On gross examination, focal vesicular and cystic lesions were identified separately from the normal-looking placental tissue. The pathologic diagnosis was CHMCF and considering the fact that placenta accreta was originally suspected, invasive hydatidiform mole was not ruled out. After radiologic work-up, metastatic lung lesions were detected, and methotrexate was administered in six cycles at intervals of every two weeks. The author presents the clinicopathological features of this unexpected CHMCF case accompanied by pulmonary metastasis, compares to literature review findings, and emphasizes the meticulous pathologic examination. Full article

The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies’ immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively (p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal. Full article