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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. [ABSTRACT FROM AUTHOR]

Introduction: Hydatidiform mole with a normally developing fetus is a rare case associated with an increased risk of bleeding, preterm birth, preeclampsia, congenital anomalies, and intrauterine fetal death.Case report: We report a case of a twin pregnancy with a hydatidiform mole and a normal fetus. The pregnancy was conceived via in vitro fertilization. The complete hydatidiform mole was diagnosed during the first screening. We extended the pregnancy until 38 weeks’ gestation. Thanks to the control of beta-human chorionic gonadotropin levels and dynamic ultrasound monitoring, the woman successfully gave birth.

Abstract Background This case describes the youngest patient documented in the literature who presented with a giant hydatidiform mole, effectively addressed through conservative treatment. Case presentation Our department received a 20-year-old Caucasian patient who was admitted due to significant metrorrhagia in an undisclosed pregnancy. During examination, we identified a massive, highly vascularized hydatidiform mole measuring 22 cm (cm). We performed a surgical dilatation and curettage. The anatomopathological findings confirmed the presence of a complete hydatidiform mole (CHM). Following the established guidelines, we conducted weekly monitoring of human chorionic gonadotropin (hCG). Unfortunately, the patient discontinued the follow-up and became pregnant again before achieving hCG negativation. Conclusion This case suggests that conservative treatment is a viable option regardless of the size of gestational trophoblastic disease (GTD), especially when the preservation of fertility is a crucial consideration, as effectively demonstrated in our case.

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. [ABSTRACT FROM AUTHOR]

Background: This case describes the youngest patient documented in the literature who presented with a giant hydatidiform mole, effectively addressed through conservative treatment. Case presentation: Our department received a 20-year-old Caucasian patient who was admitted due to significant metrorrhagia in an undisclosed pregnancy. During examination, we identified a massive, highly vascularized hydatidiform mole measuring 22 cm (cm). We performed a surgical dilatation and curettage. The anatomopathological findings confirmed the presence of a complete hydatidiform mole (CHM). Following the established guidelines, we conducted weekly monitoring of human chorionic gonadotropin (hCG). Unfortunately, the patient discontinued the follow-up and became pregnant again before achieving hCG negativation. Conclusion: This case suggests that conservative treatment is a viable option regardless of the size of gestational trophoblastic disease (GTD), especially when the preservation of fertility is a crucial consideration, as effectively demonstrated in our case. [ABSTRACT FROM AUTHOR]

Objective: To compare the age-specific clinical features of molar pregnancy and to describe the risk factors associated with this situation. Method: This retrospective case-control study was conducted at the Department of Obstetrics and Gynecology. Tepecik Education and Research Hospital, Izmir, Turkey. The participants included both adolescents (< 19 years) and adults with histologically confirmed hydatidiform moles in our institution between January 2015 and January 2022. The interventions and main outcome measures of this study involved evaluating the clinical and ultrasonographic features, as well as the risk factors, associated with molar pregnancies in adolescents. Results: This study of 137 patients with molar pregnancy found that adults had a higher incidence of partial molar pregnancy (20 patients versus seven patients) and lower beta-hCG levels than adolescents (176.890.71 mIU/ml versus 253.734.47 mIU/ml). Adolescents had a higher likelihood of hyperthyroidism (25.4% versus 9.2%). bleeding on admission (4.2% versus 1.51%),. longer hospital stays (5.44 ± 2.73 days versus 3.59 ± 3.08 days). Higher rates of uterine enlargement and postoperative bleeding (15.5% versus 1.5%). Adolescents also required more analgesia (97% versus 89.4%). Conclusions: Adolescents with Gestational trophoblastic diseases (GTD) may present with more severe symptoms compared to adults, which can lead to delayed diagnosis and treatment. Further research is needed to better understand the underlying mechanisms and risk factors for GTDs in this population. Increased awareness and education can help improve recognition and management of GTDs in adolescents and improve their overall health outcomes. [ABSTRACT FROM AUTHOR]

Background: Ectopic molar pregnancy (EMP) is a rare form of gestational trophoblastic disease that occurs when a hydatidiform mole implants outside the uterus. Case Presentation: We describe a 35-yr-old woman with mild abdominal pain, delayed menstruation for 2 months, and high beta-human chorionic gonadotropin levels. Sonography revealed a heterogeneous hyperechoic mass in the left adnexa and fluid in the endometrial cavity, suggestive of a tubal EMP. She underwent endometrial curettage and left salpingectomy. Pathology confirmed the diagnosis of invasive hydatidiform mole/left tubal EMP. The case recovered well and had no complications. Conclusion: This case highlights the need for early diagnosis and multidisciplinary treatment of EMP to avoid serious consequences from persistent trophoblastic tumors. [ABSTRACT FROM AUTHOR]

Gestational choriocarcinoma, a rare variant of gestational trophoblastic disease, typically arises from abnormal trophoblastic cell proliferation post-pregnancy, often associated with a hydatidiform mole. While most choriocarcinoma cases develop within the uterine cavity, an exceedingly rare manifestation occurs within a previous cesarean section scar. In our study, a 31-year-old woman with a history of hydatidiform mole presented with amenorrhea and spotting. Initial assessments revealed elevated beta-human chorionic gonadotropin (βhCG) levels and a heteroechoic mass at her prior cesarean section scar in sonographic examination. Histopathologic findings and the metastatic workup categorized the patient as FIGO stage I, indicating no metastasis. Due to the absence of metastasis, adjuvant chemotherapy was omitted. Total abdominal hysterectomy confirmed choriocarcinoma. Post-surgery, βhCG levels notably decreased, remaining negative during the two-year follow-up with no reported symptoms. Our findings suggest that surgical resection and meticulous βhCG monitoring may be a promising treatment strategy for non-metastatic choriocarcinoma.

المخلص: أهداف البحث: لدى مستقبلات فيتامين د أدوار كمضاد للسرطان لأنواع مختلفة من السرطانات. الهدف من هذه الدراسة هو تحديد الفروق في مستويات مستقبلات فيتامين د بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي. طرق البحث: هذه دراسة مقارنة شملت ستة وستين نسيجا تم جمعها من الورم الحويصلي المائي وورم النسيج الترويفي الحملي. تم إجراء اختبار ''تي'' واختبار ''مان ويتني'' لمقارنة التعبير المناعي لمستقبلات فيتامين د، بما في ذلك شدة مستقبلات فيتامين د، توزيع مستقبلات فيتامين د، والتقدير التاريخي بين الورم الحويصلي المائي وورم النسيج الترويفي الحملي. النتائج: تم تضمين ما مجموعه ستة وستين عينة من الأنسجة في هذه الدراسة، تتألف من سبعة وثلاثين نسيجا تم تشخيصها بالورم الحويصلي المائي وأربعة وعشرين نسيجا تم تشخيصها بورم النسيج الترويفي الحملي. تمت المقارنة بين العمر والأعداد بين المرضى الذين يعانون من الورم الحويصلي المائي والمرضى الذين يعانون من ورم النسيج الترويفي الحملي، ولم يلاحظ وجود فروقات كبيرة في كلا المجموعتين. بالنسبة لحالات ورم النسيج الترويفي الحملي، كانت شدة مستقبلات فيتامين د أقل بشكل ملحوظ من شدة مستقبلات فيتامين د في نسيج الورم الحويصلي المائي. بالإضافة إلى ذلك، كان التقدير التاريخي في نسيج ورم النسيج الترويفي الحملي أقل بشكل ملحوظ من التقدير التاريخي في نسيج الورم الحويصلي المائي. ومع ذلك، لم يكن هناك فروقات كبيرة في توزيع مستقبلات فيتامين د بين نسيج ورم النسيج الترويفي الحملي ونسيج الورم الحويصلي المائي. الاستنتاجات: كان التعبير المنخفض لمستقبلات فيتامين د مرتبطا بورم النسيج الترويفي الحملي. بالمقابل، كان التعبيرالعالي لمستقبلات فيتامين د مرتبطا بالورم الحويصلي المائي. تشير هذه النتائج إلى أن مستويات مستقبلات فيتامين د قد تلعب دورا في شدة مرض النسيج الترويفي الحملي. Abstract: Objective: Vitamin D receptor (VDR) exerts anti-cancer properties in a variety of cancers. The purpose of this study was to investigate the expression of VDR in patients with hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). Methods: This is a cross-sectional study involved 61 specimens of HM (n = 37, 60.7%) and GTN (n = 24, 39.3%) was collected from the biopsy. An immunohistochemistry was used to asses the VDR expression. Student's t-test and Mann–Whitney test were used to compare the expression of VDR, including VDR staining intensity, VDR distribution, and histoscore, between HM and GTN tissue specimens. Results: No significant differences in age and parity were noted between patients with HM or GTN (p > 0.05). The VDR staining intensity of GTN tissue specimens was significantly lower than that of HM tissue specimens (2.3 ± 0.8 vs. 2.8 ± 0.5, p = 0.008). In addition, the histoscore for GTN tissues was significantly lower than that for HM tissues (7.3 ± 3.2 vs. 9.4 ± 28, p = 0.016). However, no significant differences in VDR distribution between GTN and HM tissues were observed (3.3 ± 0.8 vs. 3.3 ± 1.0, p = 0.525). Conclusion: Low VDR expression is associated with GTN, whereas high VDR expression is associated with HM, suggesting that the expression of VDR may regulate the severity of gestational trophoblastic disease.

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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.

Accurately interpreting persistent, low human chorionic gonadotropin (hCG) levels is essential for managing gestational trophoblastic disease. Erroneous interpretation can lead to inappropriate interventions, including unnecessary chemotherapy or hysterectomy, or unjustified changes in chemotherapeutic regimens due to misidentification of a false-positive hCG as a true positive. The predominant etiology of phantom hCG is the presence of heterophilic antibodies. Consequently, screening for urine hCG is indispensable for its diagnosis because immunoglobulin is not generally present in urine. Here, we report about phantom hCG after a complete hydatidiform mole. Initial urine hCG evaluations were negative, although the serum hCG levels remained positive, leading to the diagnosis of phantom hCG. After subsequent delivery, urine hCG levels persisted at diminished levels. However, a different assay yielded negative hCG results for both serum and urine samples. The patient subsequently gave birth. The absence of hCG was consistently confirmed over five years. [ABSTRACT FROM AUTHOR]

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.

Background: The incidence of molar pregnancy has demonstrated marked geographic and ethnic differences. This difference in the prevalence across various countries perhaps may depend upon the socioeconomic, genetic, nutritional and other cultural factors. In spite of having a higher prevalence among Asians, still epidemiological characteristics of Gestational Trophoblastic Disease (GTD) or Gestational Trophoblastic Neoplasia (GTN) are difficult to determine secondary to inconsistencies in case definitions and lack of centralised databases. Hence, this study was undertaken to determine the proportion and the clinical profile of women with hydatidiform mole from a South Indian population, where as of now there is limited data to enable us to detect and provide the standard of care for patients with GTN. Materials and Methods: A prospective cohort study between August 2014 to December 2015 and a retrospective review of medical records for the preceding 2 years from the year 2012 to 2014 was conducted in JIPMER to determine the proportion of women with molar pregnancy as well as to study the clinico-epidemiologic profile of hydatidiform mole. The study population comprised of a total of 116 cases, of which, 68 cases belonged to the prospective group and 48 cases to the retrospective group. The patients belonging to the prospective group (68) were followed up for a period of 6 months to note the trend of the β HCG and to detect the occurrence of GTN. The patients in the retrospective group (48) were considered only for analysing the clinical profile of hydatidiform mole, as follow up was not possible for this group of patients. Results: The proportion of molar pregnancy was calculated to be 2.07 per 1000 live births. Majority (59%) of the study population belonged to the age group of 18-23 years. Almost all the patients (98%) belonged to lower socioeconomic group. More than one-third (48%) of the patients were nulliparous. It was observed that, greater than half of the patients (56%) presented between 11-15 weeks of amenorrhoea. Majority (76%) of the patients had no previous abortions in their obstetric history. Only 4 (3.45%) patients had previous history of molar pregnancy. Abnormal uterine bleeding was the most common complaint noted in 79% of patients. Nausea and vomiting were noted in 62 patients, out of which 25 (40%) presented with hyperemesis requiring fluid and electrolyte correction. Anaemia was the most common medical complication noted in 55% of patients, followed by hyperthyroidism in 33% and hypertension in 2% patients. Among the 116 patients, 74(64%) had preevacuation HCG level more than 2,00,000mIU/ml. Suction evacuation was done in all the cases and 9 (8%) patients required re-evacuation in view of residual vesicular mole on a check scan. Among the 116 patients, histopathology revealed complete mole in 88% patients and partial mole in 12%. In the prospective group, following suction evacuation, 79% of the patients attained remission by the end of 6 months whereas in 13 patients (21%), hCG continued to either plateau or increase following the primary evacuation and they further developed GTN requiring chemotherapy. Out of the 13 cases of GTN, 7 patients attained remission with chemotherapy, whereas 6 patients failed to achieve remission during the 6 months' study period. Conclusion: Young, nulliparous women belonging to low socio-economic status had a higher proportion of hydatidiform mole. Improving the literacy rates, creating awareness among the women, early registration of pregnancy, prompt referral to higher centres and early administration of appropriate treatment, with a vigilant follow up would help in early detection of GTN.There is also a need for studies at country level which will give us a national figure on molar pregnancies. Thus, a standardized clinicoepidemiological profile of molar pregnancy in India can be created. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hydatidiform mole is a condition characterised by abnormal trophoblastic hyperplasia and failure of embryonic tissue development. The risk of recurrence is seen to be associated with biallelic maternal mutations in NLRP7, KHDC3 L and PAD16 genes. Women with such mutations have a major risk of reproductive failure and normal pregnancy is seen in only 1.8%. We report the case of a 31‑year‑old woman with previous three molar pregnancies who on genetic testing was found to be compound heterozygous for pathogenic variants in the NLRP7 gene (c.2738A>G and c.2078G>C). Accordingly, the woman was counselled regarding assisted reproduction with oocyte donation for a normal pregnancy outcome. At present, the patient has an ongoing 5‑month pregnancy through oocyte donation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cases of hydatidiform moles with a coexisting fetus are sparse and patients are at high risk for severe complications. Patients and physicians often face the dilemma of the wish to continue pregnancy until viability of the fetus while the risk for maternal complications increases. We present an educational case of a twin pregnancy presenting with a hydatidiform mole and coexisting normal fetus with a placenta praevia. The patient developed severe, early onset preeclampsia with beginning HELLP-syndrome and was tested Covid-19 positive in the further course. Termination of pregnancy was conducted via caesarean section at 18 + 6 weeks of pregnancy. Histopathology and genetic analysis confirmed a complete hydatidiform mole next to a normal placenta. Close follow-up examinations were conducted and showed normal findings including ß HCG levels normalizing within 5 months. This case combines several rare, difficult and severe medical conditions and demonstrates how an individualized therapy by an interdisciplinary team covering a highly sensitive topic was developed in a situation where no guidelines exist.

Nephrotic syndrome (NS) during pregnancy is a fairly rare pathology and its descriptions in the literature are few. For a long time, NS was associated only with an exacerbation of chronic glomerulonephritis or de novo nephritis, however, the experience of recent years has shown that NS can be a manifestation of the classical obstetric pathology preeclampsia (PE). The appearance of massive proteinuria with the development of NS is most typical for early PE, which, of course, makes diagnosis difficult, especially if PE develops at an unusually early time (up to 20 weeks). To describe PE that does not fit into the classical criteria, the term atypical PE is now used, the development of which can be promoted by both obstetric and somatic risk factors. The presented clinical observation describes the development of early (within 14 weeks) severe PE with the NS at the onset of the disease in a patient with the first multiple pregnancy and complete hydatidiform mole (HM) of one of the fetuses. The progression of nephropathy with the addition of thrombotic microangiopathy and HELLP syndrome made it possible to assume the diagnosis of PE with a high probability. The rapid relief of all clinical manifestations after delivery confirmed this assumption. The role of HM as the main trigger of unusually early PE is discussed. Apparently, the patient's trophoblast disease in the form of hydatidiform mole caused the formation of a severe angiogenic imbalance already in the early stages of pregnancy, which led to the development of PE, which manifested NS as a consequence of podocytopathy due to VEGF deficiency. Thus, the development of NS in a pregnant patient without a history of kidney disease dictates, first of all, the exclusion of PE, until proven otherwise.

Siti Salima,1 Mulyohadi Hadi Wibowo,1 Birgitta M Dewayani,2 Aisyah Shofiatun Nisa,1 Firas Farisi Alkaff3,4 1Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia; 2Department of Pathology of Anatomy, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia; 3Division of Pharmacology and Therapy, Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia; 4Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, Groningen, the NetherlandsCorrespondence: Siti Salima, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, Indonesia, Tel +62811223830, Email s.salima@unpad.ac.id Firas Farisi Alkaff, Division of Pharmacology and Therapy, Department of Anatomy, Histology, and Pharmacology, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia, Tel +6281330101993, Email f.f.alkaff@umcg.nl; firasfarisialkaff@fk.unair.ac.idAbstract: Hydatidiform mole (HM) is an aberrant pregnancy characterized by atypical trophoblastic hyperplasia, hydropic chorionic villi, and deprived fetal development. There are two types of HM, ie, complete (CHM) and partial (PHM). Both CHM and PHM can recur; however, the recurrence of PHM is very scarce compared to CHM. In this report, we present a case of a 33-year-old woman with recurrent PHM for 7 times without any normal pregnancy in-between. PHM was determined by histology examination. The patient underwent suction curettage and was followed up with serial β-hCG levels. Recurrent PHM, although rare, is associated with an increased incidence of malignancy. A series of clinical and β-hCG evaluation should be warranted because of the possibility of gestational trophoblastic neoplasia development.Keywords: hydatidiform mole, pregnancy, partial hydatidiform mole, case report

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.

BackgroundPost-molar gestational trophoblastic neoplasia (pGTN) develops in about 15% to 20% of complete hydatidiform mole (CMH). Commonly, pGTN is diagnosed based on hCG monitoring following the molar evacuation. To date, no detailed information is available on how fast can pGTN develop from CHM. However, the concurrence of CHM and pGTN is extremely rare.Case presentationA 29-year-old woman presented to the gynecology department with irregular vaginal bleeding and an elevated hCG serum level. Both ultrasound and MRI showed heterogeneous mass in uterine cavity and myometrium. Suction evacuation was performed and histologic examination of the evacuated specimen confirmed complete hydatidiform mole. Repeated ultrasound showed significant enlargement of the myometrium mass one week after the evacuation. pGTN with prognostic score of 4 was then diagnosed and multi-agent chemotherapy regimen implemented with a good prognosis.ConclusionIn rare cases, CMH can rapidly progress into pGTN. Imaging in combination with hCG surveillance seems to play a vital role guiding timely diagnosis and treatment in the specific condition. Low-risk gestational trophoblastic neoplasia (GTN) should be managed stratified according to the individual situation.

Gestational trophoblastic disease (GTD) is an abnormal pregnancy caused by the placenta, which can potentially metastasise. Suction evacuation is recommended for diagnosis and treatment, and dilatation and evacuation (D&E) is usually performed under intravenous anaesthesia due to the short operation time and minimal blood loss. We refer to the guidelines produced by the Japan Society of Obstetrics and Gynaecology (JSOG), and acknowledge that practices vary globally. However, to the best of our knowledge, there is no evidence on perioperative management and arrangements in D&E required for managing giant hydatidiform moles, such as preventing massive haemorrhage, respiratory dysfunction with a pathogenesis like ovarian hyperstimulation syndrome (OHSS), or intensive care needs. This case report describes perioperative considerations for managing a giant hydatidiform mole using D&E in a uterus enlarged to the third-trimester pregnancy size. A 28-year-old multiparous woman was clinically diagnosed with a hydatidiform mole after a spontaneous miscarriage due to abnormal genital bleeding, systemic oedema, and abdominal distention. Ultrasound and computed tomography showed a ballooning uterus with a third-trimester pregnancy size, a robust intrauterine mass, and ascites. Serum hCG levels were extremely high (>3,000,000 mIU/mL), confirming the clinical diagnosis of a hydatidiform mole. Emergency D&E was safely performed under multidisciplinary perioperative management, with careful preparation and support. This is a rare experience-based case report and valuable documentation detailing multidisciplinary perioperative management under general anaesthesia. To the best of our knowledge, this is the first report describing the considerations, details, and innovations required in the perioperative management of giant hydatidiform moles using D&E.

Objectives: Human chorionic gonadotropin (hCG) levels are essential for the management of trophoblastic diseases. This study aimed to compare the sensitivities and relationships of two hCG measurement methods (total hCG and the free β-subunit of hCG) in managing gestational trophoblastic disease (GTD). Design and Methods: We analyzed data from patients treated for GTD at Chiba University Hospital between 2008 and 2019. We focused on cases where both total hCG (mIU/mL) and the free β-subunit of hCG (ng/mL) were measured on the same day. Results: Out of 80 patients (mean age 38.9 ± 11.7 years) and 158 measurements, 26 had values below the sensitivity threshold for both tests. Fifty-nine measurements were positive for total hCG but below the sensitivity threshold for the free β-subunit of hCG, whereas only two showed the opposite. Seventy-one measurements were positive for both total hCG and the free β-subunit of hCG. There was a significant correlation between total hCG and the free β-subunit of hCG with both positive values, (r = 0.94, p

HIGHLIGHTS • This study aimed to identify the characteristics of Gestational Trophoblastic Neoplasia (GTN). • GTN is chemosensitive, but without appropriate therapy and follow-up, GTN will develop into complications and fatalities. ABSTRACT Objective: Gestational Trophoblastic Neoplasia (GTN) is a pregnancy-related malignancy due to abnormal proliferation of trophoblastic tissue. This study aimed to identify the characteristics of patients with GTN to help diagnose cases of GTN earlier and provide better treatment. Materials and Methods: This was a descriptive retrospective study on medical records of patients with GTN in Dr. Soetomo General Academic Hospital Surabaya, Indonesia, during the period of January 2018 to December 2020 with a total sampling technique. There were 41 patients with GTN included as study subjects. Results: Forty-one cases of GTN met the inclusion criteria out of the fifty medical records collected. The majority of patients aged 21 – 30 years old (34%) and had parity status without data (42%). Regarding the clinical profile based on prognostic factors, the predominant patients (71%) also had no data about the time interval between the end of the last pregnancy and the first time diagnosed by GTN, Those with more than 100,000 mIU/ml of beta-hCG levels were 32%, and those without metastases were 41.5%. Most patients belonged to the low-risk group (49%) and received chemotherapy (71%) with the MTX LD regimen (69%). Conclusion: GTN occurred predominantly in reproductive women that belonged to the low-risk group. Furthermore, chemotherapy is one of the chosen therapy for those patients.

Background and Objective: Gestational trophoblastic disease refers to a specific range of trophoblast proliferative disorders that originate from the placental epithelium. Recently, hematological indices are being researched and discussed as an easy and accessible method to identify patients and monitor disease progression. Therefore, the present study was conducted to investigate the relationship between the levels of hematological indicators and hydatidiform mole progression. Methods: This cross-sectional study was conducted on 164 patients diagnosed with hydatidiform mole in two groups: complete hydatidiform mole (132 people) and partial hydatidiform mole (32 people). The diagnosis of the disease was made based on the pathology results recorded in the patients' files. Information related to hematological, biochemical and hormonal indices was collected and analyzed. Findings: In general, there was no statistically significant difference between the group of complete hydatidiform mole and partial mole in terms of age, body mass index, uterine size, incidence rate of Theca lutein cyst and cyst size, gravida, parity, miscarriage, and history of previous mole. Of all laboratory markers evaluated (such as WBC, PLT, MPV/PLT, AST/PLT, RDW/PLT), only the mean level of triiodothyronine (free T3) in the complete mole group (1.50±2.40 pmol/L) was significantly lower compared to the partial mole group (1.90±1.30 pmol/L) (p=0.004). Free T3 threshold (1.54±0.87 pmol/L) showed good sensitivity (74.60%), specificity (51.50%) and 50% accuracy to distinguish complete moles from others. Conclusion: This study showed that a high level of free T3 may be a good marker for the diagnosis of hydatidiform mole, which may be useful in the early detection of moles undetectable on ultrasound.

Abstract Background Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary. Methods In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score. Results Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome3, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.

Hydatidiform mole with the coexisting live fetus is a rare entity occurring in 0.005%–0.01% of all pregnancies. With the introduction of assisted reproductive techniques (ARTs), a significant rise in the incidence of multiple pregnancies has been reported. Here, we report two cases of molar pregnancies with a coexisting live fetus conceived following assisted conception. In our first case, pregnancy was continued and delivered a term live infant. The second case was aborted at 16 weeks' gestation due to maternal complications. These two patients needed chemotherapy due to persistent gestational trophoblastic disease. The rarity of this condition poses several diagnostic and management challenges, especially conceiving after ART the decision of termination for such couples.

Abstract Objective To evaluate whether prophylactic chemotherapy (P-chem) increased the drug resistance rate of postmolar GTN and whether the first-line chemotherapy should be different from P-chem. Methods Postmolar GTN received P-Chem was defined as P-Chem group. Postmolar GTN without P-chem was randomly selected as control group according to the ratio of 1:3 (P-chem:control) and matched by age for low risk and high risk GTN separately. Results Totally 455 low-risk and 32 high-risk postmolar GTN patients were included. WHO risk score, chemotherapy cycles to achieve hCG normalization and resistant rate were similar between P-chem (27 cases) and control (81 cases) group. Among low-risk GTN patients, interval from hydatidiform mole to GTN was significantly longer in P-chem group than control (44 vs 69 days, P = 0.001). Total chemotherapy cycles and resistant rate were similar between low-risk GTN treated with same agent as P-chem (group A) and alternative agent (group B). But group A needed more chemotherapy cycles to achieve hCG normalization than group B. Conclusions P-chem delayed the time to GTN diagnosis, but didn’t increase risk score or lead to drug resistance of postmolar GTN. Alternative agent different from P-chem had the potential of enhancing chemotherapy response in low- risk postmolar GTN.

OBJECTIVE: To determine the diagnostic accuracy of ultrasound in detection of molar pregnancy taking histopathological findings as a gold standard. METHODS: This study was conducted in Khyber Teaching Hospital, Peshawar, Pakistan. All pregnant females of 15-45 years’ age; with clinical, biochemical suspicion and definite diagnosis of molar pregnancy were included in our study. Patients already diagnosed on histopathology as hydatidiform mole, missed miscarriage and invasive mole were excluded from the study. Informed consent, brief history, baseline Investigations, serum beta Human Chorionic Gonadotropin levels were obtained. Suspected cases of hydatidiform mole (n=212) on Transabdominal Ultrasound scans were referred to gynecologist for histopathological diagnosis and management. Histopathology of samples were compared to ultrasound report. Data was collected was analyzed by SPSS v.23.0. RESULTS: Mean age of patients was 29.04±8.23 years. Molar pregnancies were reported in 119 (56.13%) and 124 (58.49%) cases through ultrasound and histopathology respectively. Ultrasound findings suggestive of complete molar pregnancy in 79 (37.2%) cases, as compared to 85 (40.09%) cases by histopathology. Majority (n=35; 58.3%) of the molar pregnancy were found in patients having 31-40 years of age. Ultrasound and histopathology showed agreement in diagnosis of molar pregnancy in 103/156 (66%) cases and non-molar pregnancy in 40/56 (71.4%) cases. Sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy of Ultrasound in diagnosis of molar pregnancy were 66.03%, 71.43%, 86.55% 43.01% and 67.45% respectively. CONCLUSION: Overall diagnostic accuracy of ultrasound in diagnosis of molar pregnancy is 67.45% and may be used in early detection of molar pregnancy.

Trophoblastic neoplasias are rare tumors, accounting for less than 1 % of malignant neoplasms of the female genital tract. Trophoblastic tumors associated with developing pregnancy are extremely rare. The article presents the successful experience of diagnostics and treatment of intraplacental chorioncarcinoma associated with progressing pregnancy.

Background: The molar and non-molar lesions are determined during histomorphological examination and treated as inconclusive. The establishing of a marker by immunohistochemical investigations could influence the accuracy of the morphopathological diagnosis. The aim is evaluation of p57 immunoexpression in the trophoblastic germ compartment in molar and non-molar pregnancies. Material and methods: Abortion products from 15 patients with hydatidiform mole, 18 pregnancies solved on social indications and 16 short-term disordered pregnancies were evaluated depending on the immunoexpresion of p57. Results: The hydatidiform mole was classified based on anti-p57 immunoexpression into: complete hydatidiform mole – 8 cases (negative immunoexpression or expression in ˂10% of villous cytotrophoblast) and partial hydatidiform mole – 7 cases (positive expression in ˃10% of the villous cytotrophoblast). Basal deciduous and extravillous cytotrophoblasts were positive in 100% of cases and served as internal control. Hepatocytes were used as negative control. In the control group, the positive immunoexpression was attested in >10% of cases in the villous trophoblast. Conclusions: Differential immunoexpression of p57 protein in the germinal cytotrophoblast allows subclassification of molar pathology into complete and partial forms, while not allowing the differentiation between partial hydatidiform mole and non-molar lesions. Immunohistochemical evaluation of p57kip2 protein in molar and non-molar pathology is useful in differential diagnosis as a complementary method.

Background: The hydatiform mole is charcaterized by a pathological proliferation of the trophoblast. Its evaluation could predict the progression to gestational trophoblastic neoplasia. The aim of the study was the analysis of the proliferative activity of the villous trophoblast in the molar vs non-molar lesions. Material and methods: p-57 and Ki-67 were evaluated by immunohistochemistry in 15 cases of hydatidiform mole and 18 cases of abortions. Results: The hydatidiform mole was divided based on the immunoexpression of anti-p57 into: complete (8 cases) and partial type (7 cases). The distribution score of Ki67 immunoreactivity in the villous cytotrophoblast was: complete mole: +3 – 8 cases; partial mole: +1 – 1 case, +2 – 3 cases, +3 – 3 cases; abortions on social indications: +1 – 6 cases, +2 – 9 cases; +3 – 2 cases. The mean and standard deviations were: 2.88±0.354; 2.29±0.756 and 1.82±0.728, respectively. The following statistical correlations were determined: complete vs partial mole (p=0.014), complete mole vs abortion (p

Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT).

Introduction. The reproductive experience of women 18–44 years of age is quantitatively superior to adolescent girls. The structure of reproductive losses of adolescents, its identity or difference in comparison with women of reproductive age is extremely unexplored.Aim. To compare the structure of reproductive losses of adolescents and women of reproductive age on the example of the Tyumen region.Materials and methods. A retro-prospective analytical study carried out. Study period – 2016–2021. Adolescent girls and women of reproductive age with completed pregnancies included.Results and discussion. In the Tyumen region, the frequency of reproductive losses approaches childbirth (42.83% and 57.17%), mainly represented by medical abortion (59.98%). The proportion of completed pregnancies among adolescent girls (1.14%) is inferior to women of reproductive age (98.86%). Adolescent girls are characterized by the completion of pregnancy by childbirth (OR = 1.68), a high frequency of medical abortion (OR = 1.71). Reproductive losses up to 12 weeks distinguish completed pregnancies in women of reproductive age (OR = 1.68); unsuccessful abortion attempt, criminal and unspecified types of abortion before 12 weeks and other abnormal products of conception after 12 weeks are their exclusive markers. The pregnancy outcome is associated with age: with adolescents – medical abortion before (OR = 1.71) and after 12 weeks (OR = 2.01); with reproductive age – other abnormal products of conception (OR = 1.64) and ectopic pregnancy (OR = 6.15). Reproductive losses are associated with gestational age before/after 12 weeks: with adolescents – spontaneous abortion after 12 weeks (OR = 2.55); with reproductive age – other types of abortion (OR = 20.37), medical abortion (OR = 1.93), other abnormal products of conception (OR = 1.89) before 12 weeks and spontaneous abortion (OR = 5.42) after 12 weeks.Conclusion. In the Tyumen region, reproductive losses in frequency compete with childbirth. Augmented the concept of the abortion-contraceptive behavior of modern society based on the association of medical abortion with adolescent girls that we have identified. The structure of reproductive losses is associated with a woman’s age period and gestational age.

Purpose: This study aimed to determine the occurrence rate of gestational trophoblastic neoplasia (GTN) and its related factors in aged women with hydatidiform mole (HM) in Tu Du Hospital, Vietnam. Materials and Methods: This retrospective cohort study included 372 women aged ≥40 years with HM diagnosed through postabortion histopathological assessment in Tu Du Hospital from January 2016 to March 2019. Survival analysis was used for GTN cumulative rate estimation, log-rank test for group comparison, and Cox regression model for determining GTN-related factors. Results: After a 2-year follow-up, 123 patients were found to have GTN at a rate of 33.06% [95% confidence interval (CI): 28.30– 38.10]. GTN occurrence meant that the time was 4.15±2.93 weeks with peaks at week 2 and 3 after curettage abortion. The GTN rate was remarkably higher in the ≥46-year age group than in the 40-to-45-year age group [hazard ratio (HR)=1.63; 95%CI: 1.09– 2.44], as was the vaginal bleeding group compared to the non-bleeding group (HR=1.85; 95%CI: 1.16–2.96). Preventive hysterectomy and preventive chemotherapy plus hysterectomy in the intervention group reduced the GTN risk compared to the no intervention group at HRs of 0.16 (95%CI: 0.09–0.30) and 0.09 (95%CI: 0.04–0.21), respectively. Chemoprophylaxis failed to decrease the GTN risk when comparing the two groups. Conclusion: Post-molar pregnancy GTN rate in aged patients was 33.06%, much higher than that of the general population. Preventive hysterectomy or chemoprophylaxis plus hysterectomy are effective treatment methods to support GTN risk reduction. [ABSTRACT FROM AUTHOR]

Background: Complete and partial moles (PM) are the most common gestational trophoblastic diseases. Due to some overlapping morphological findings, ancillary studies may be necessary. Methods: In this cross-sectional study, 47 cases of complete mole (CM) and 40 cases of PM were randomly selected based on histopathological criteria. Only those cases that were agreed upon by two expert gynecological pathologists and confirmed by the P57 IHC study were included. The expression level of the Twist-1 marker in villi stromal cells, as well as syncytiotrophoblasts, was evaluated quantitatively (percentage of positive cells), qualitatively (staining intensity) and as a total comprehensive score. Results: Expression of Twist-1 is higher and more intense in villous stromal cells of CMs (p < 0.001). Moderate to strong staining intensity in more than 50% of villous stromal cells, can differentiate CM and PM with 89.5% sensitivity and 75% specificity. In syncytiotrophoblasts of CM, Twist-1 expression was significantly lower than PM (p < 0.001). Negative or weak staining intensity in less than 10% of syncytiotrophoblasts, can distinguish CM and PM with 82.9% sensitivity and 60% specificity. Conclusion: A higher expression of Twist-1 in villous stromal cells of hydatidiform moles is a sensitive and specific marker for the diagnosis of CMs. An elevated expression of this marker in villous stromal cells suggests another pathogenic mechanism for more aggressiveness of CMs in addition to the characteristics of trophoblast cells. The opposite result was obtained in the expression of Twist-1 in the syncytiotrophoblasts, compatible with defects in the process of formation of these supportive cells in CMs. [ABSTRACT FROM AUTHOR]