Search Results (51)

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: Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this protein in other molecular pathways involving inflammation, apoptosis, and glucose metabolism. Methods: This review aims to highlight the importance of TXNIP in diabetes-related pathophysiology and explore the existing evidence regarding TXNIP’s role in GDM-associated pathogenetic mechanisms, revealing common regulatory pathways. Results: Among other complex diseases, TXNIP has been found upregulated in diabetic pancreatic beta cells, thus contributing to diabetes pathogenesis and its related complications. In addition, depletion of TXNIP has been shown to decrease the negative consequences of excessive stress in various cellular systems and diseases, pointing towards a potential therapeutic target. In line with these findings, TXNIP has been investigated in the pathogenesis of Gestational Diabetes Mellitus (GDM), a common pregnancy complication affecting the mother and the neonate. Overexpression of TXNIP has been found in GDM placentas or trophoblast cell lines mimicking GDM conditions and has been associated with key dysregulated mechanisms of GDM pathophysiology, like oxidative stress, inflammation, apoptosis, impaired autophagy, altered trophoblast behavior, and placental morphology. Interestingly, TXNIP has been found upregulated in GDM maternal serum and downregulated in umbilical cord blood, indicating potential compensatory protective mechanisms to GDM-related oxidative stress. Conclusions: Due to its contribution to the regulation of critical cellular processes such as inflammation, metabolism, and apoptosis, TXNIP finds its place in the pathophysiology of gestational diabetes through a currently limited number of scientific reports. Full article

Background: Gestational trophoblastic diseases comprise the hydatiform moles (HMs), complete or partial, an abnormal development of trophoblastic tissue. HMs derive from a gametogenesis error during conception leading to an anomalous chromosomal asset. In the complete hydatiform mole (CHM), when one or two spermatozoa enter an empty oocyte, the karyotype, paternally derived, is diploid 46,XX or 46,XY. CHM is characterized by massive hydropic degeneration of the villi, with no fetal structures, easily detected by ultrasound (US) in early gestation, confirmed by elevated maternal beta-hCG levels. CHM with coexistent fetus (CHMCF) is an exceptional event with a high risk of malignant progression, and severe complications such as massive vaginal bleeding, preeclampsia, and fetal death. Methods/Results: We present a case of CHMCF in a 29-year-old woman, which resulted in a liveborn and healthy baby at 38 weeks of gestation. The patient was prenatally carefully monitored with biweekly US and periodic beta-hCG levels. Post-partum follow-up consisted of transvaginal US and beta-hCG levels at 1, 3, and 6 months. After 1 year post-delivery, both the mother and the newborn were healthy. Conclusions: CHMCF management can be challenging as shared guidelines are currently lacking and the case described may be helpful in adding more data. 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

Background: Laeverin is an extravillous trophoblast marker playing a significant role in trophoblast migration. We endeavored to estimate the association between the amniotic and serum laeverin concentrations at 16–22 weeks of gestation and the fetal and placental ultrasound measurements in high-risk uncomplicated pregnancies. Methods: A prospective cross-sectional study of consecutively recruited singleton pregnancies undergoing amniocentesis was performed. Fetal structural malformations and/or aneuploidy were the exclusion criteria. Fetal biometric parameters and placental growth/perfusion were assessed by ultrasound in 44 high-risk pregnancies who had no pregnancy complications and any other chronic disease. Maternal serum and amniotic laeverin levels were essayed with sandwich enzyme-linked immunosorbent assay. Results: Serum laeverin levels are decreasing marginally with the maternal age in mid-gestation. Laeverin levels in the serum correlated minimally negatively with head size of the fetus (β = −0.38; p < 0.05; 95% confidence interval (CI) −0.03–0.01), whereas the amniotic level correlated strongly with the fetal abdominal circumference (β = −0.74; p < 0.05; 95% CI: −0.34–−0.09). In addition, the amniotic laeverin level correlated moderately and positively with the placental volume (β = 0.46; p < 0.05; 95% CI: 0.01–0.08). Conclusions: Laeverin levels detected in the serum and in the amniotic fluid denote the fetoplacental growth in uncomplicated high-risk pregnancies. Full article

Intraplacental choriocarcinoma (IC) is a gestational trophoblastic neoplasia located within the placenta. Due to its silent presentation, more than half of the cases are diagnosed incidentally. An association with fetomaternal hemorrhage (FMH), stillbirth, and intrauterine growth restriction has been found. The aim of this review is to describe the clinical management of this rare condition stemming from a case report of an incidental diagnosis following an emergency cesarean section, and taking into account the available literature. Emergency interventions and examination of the placenta, even for the smallest IC lesion can ensure timely treatment and improve maternal and fetal outcomes. Full article

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms. 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

Background and Objectives: Choriocarcinoma is an aggressive oncological disease that manifests as trophoblast tissue proliferation. The vast majority of primary lesions affect the uterus, with primarily extrauterine lesions being a rarity. Choriocarcinoma with an ongoing pregnancy is extremely rare because fetuses usually do not survive the third trimester. Case Report: We present a case of heterotopic tubal choriocarcinoma coexisting with a viable intrauterine pregnancy. A 30-year-old, 39-week pregnant woman (gravida 2, para 2) came to our hospital complaining of acute upper abdominal pain. During routine prenatal screening in the first trimester, no pathological ultrasound findings were detected. Similar abdominal pain episodes had been recorded at 18, 27, and 32 weeks of gestation, when patient was hospitalized for examination and observation, but the cause of symptoms at that time of gestation remained unclear. The patient underwent an emergency caesarean section due to severe abdominal pain and fetal compromise. She delivered a live male infant. During the surgery, around 1000 mL of blood clots were evacuated, and the excision of the right fallopian tube and masses, as well as the control of significant blood loss was performed. Postoperative serum beta-hCG was elevated to 139 482 IU/L, while imaging studies showed no metastasis. The histological examination of the excised tissue samples confirmed a diagnosis of tubal choriocarcinoma. With a FIGO score of 8, the patient received three courses of the EP/EMA regimen. After more than a year, the patient showed no radiographic signs of distant metastasis and is now in complete remission. Conclusions: This case highlights the diagnostic complexity of such extremely rare scenarios. Even though such cases are rare, it demonstrates the necessity for improved diagnostic measures to enhance patient outcomes in similar clinical situations. Full article

Prevention of pregnancy complications related to the “great obstetrical syndromes” (preeclampsia, fetal growth restriction, spontaneous preterm labor, and stillbirth) is a global research and clinical management priority. These syndromes share many common pathophysiological mechanisms that may contribute to altered placental development and function. The resulting adverse pregnancy outcomes are associated with increased maternal and perinatal morbidity and mortality and increased post-partum risk of cardiometabolic disease. Maternal nutritional and environmental factors are known to play a significant role in altering bidirectional communication between fetal-derived trophoblast cells and maternal decidual cells and contribute to abnormal placentation. As a result, lifestyle-based interventions have increasingly been recommended before, during, and after pregnancy, in order to reduce maternal and perinatal morbidity and mortality and decrease long-term risk. Antenatal screening strategies have been developed following extensive studies in diverse populations. Multivariate preeclampsia screening using a combination of maternal, biophysical, and serum biochemical markers is recommended at 11–14 weeks’ gestation and can be performed at the same time as the first-trimester ultrasound and blood tests. Women identified as high-risk can be offered prophylactic low dose aspirin and monitored with angiogenic factor assessment from 22 weeks’ gestation, in combination with clinical assessment, serum biochemistry, and ultrasound. Lifestyle factors can be reassessed during counseling related to antenatal screening interventions. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care that has the potential to significantly reduce pregnancy complications and associated later life cardiometabolic adverse outcomes. 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

Galectin-13 (Gal-13) is predominantly produced by the syncytiotrophoblast, while laeverin is expressed on the outgrowing extravillous trophoblast, and both are thought to be biomarkers of preeclampsia. The aim of this study was to assess the correlation between concentrations of Gal-13 and laeverin measured in maternal serum and amniotic fluid at 16–22 weeks of gestation and the sonographic assessment of the fetoplacental measurements. Fetal biometric data and placental volume and perfusion indices were measured in 62 singleton pregnancies. Serum and amniotic levels of Gal-13 and laeverin levels were measured using a sandwich ELISA. Both amniotic fluid and serum Gal-13 levels expressed a negative correlation to the plasma laeverin level in mid-pregnancy. Serum laeverin level correlated positively with the gestational length at delivery (β = 0.39, p < 0.05), while the amniotic laeverin level correlated well with the abdominal circumference of the fetus (β = 0.44, p < 0.05). Furthermore, laeverin level in the amnion correlated positively with the estimated fetal weight (β = 0.48, p < 0.05) and with the placental volume (β = 0.32, p < 0.05). Logistic regression analyses revealed that a higher circulating Gal-13 level represents a slightly significant risk factor (OR: 1.01) for hypertension-related diseases during pregnancy. It is a novelty that laeverin can be detected in the amniotic fluid, and amnion laeverin concentration represents a potential biomarker of fetoplacental growth. Full article

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes. Full article

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20–45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types. However, other non-immune cells, such as trophoblast cells, are important in immune pregnancy regulation. Numerous studies have shed light on the crucial roles of several cytokines that regulate the inflammatory processes that characterize the interface between the fetus and the mother throughout normal porcine gestation, but most of these reports are limited to the implantational and peri-implantational periods. Increase in some proinflammatory cytokines have been found in other gestational periods, such as placental remodeling. Porcine immune changes during delivery have not been studied as deeply as in other species. This review details some of the immune system cells actively involved in the fetomaternal interface during porcine gestation, as well as the principal cells, cytokines, and molecules, such as antibodies, that play crucial roles in sow pregnancy, both in early and mid-to-late gestation. 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