Hydatidiform Research Articles

Plasma Free Amino Acid and Carnitine Levels in Pregnant Women with Hydatidiform Mole: A Case-Controlled Study

Background: To determine plasma free amino acid (FAA) and carnitine levels in pregnant women with hydatidiform mole (HM). Materials and Methods: Twenty-three pregnant women with HM, and 24 healthy pregnant wo-men as controls were enrolled in the study. FAA and carnitine concentrations were measured in plasma using liquid chromatography/tandem mass spectrometry (LC-MS). Results: The levels of alanine, arginine, and valine from the 14 amino acids examined were signif-icantly lower in the HM group than in the healthy group (p = 0.019, p = 0.009, and p = 0.03, respec-tively). In addition, several carnitines, C8DC, C16:1, and C18, of the 27 carnitines examined were significantly higher in the HM group than in the control group (p = 0.021, p = 0.03, and p = 0.021, respectively). Conclusions: This study demonstrated that a decrease in some plasma FAAs and an increase in some plasma carnitine levels might be effective in the pathogenesis of HM.

The prevalence of molar pregnancy among patients with incomplete miscarriage at a maternity teaching hospital

Background and objective: Gestational trophoblastic disease (GTD) involves a range of interrelated disorders that originate from the placenta; it can be benign or malignant. In the Kurdistan region of Iraq, data about GTD and its consequences is scarce. This study aims to identify the prevalence of GTD and its types among a cohort of Kurdish women. Methods: A cross-sectional study was conducted for a one-year duration from April 1, 2020, to April 1, 2021, at the Emergency Department of Maternity Teaching Hospital, Erbil City. Pregnant women in their first trimester and early second trimester (4–14 weeks of gestation) with vaginal bleeding, pregnant women with vaginal bleeding due to incomplete miscarriage, and pregnant women with a history of missed miscarriage were included in the study. A specialized questionnaire was prepared for the purpose of data collection. Results: Out of 380 incomplete miscarriage cases who were interviewed, fifty patients with gestational trophoblastic disease were included in the current study. The prevalence of GTD was 13.1%, and the majority of patients had a partial type of GTD. The current analysis indicated that there was a statistically significant association between the types of GTD, the personal history of molar pregnancy, and the age of participants. The analysis indicated that there is no statistical association between parity, blood group, and history of miscarriage and the type of GTD. Conclusion: The prevalence of GTD was remarkably high, and the partial type of GTD was the most common form present among the participants. The majority of the cases were diagnosed during the first trimester of the pregnancy. Complete GTD was more common among patients of advanced age.

Complete hydatidiform mole with a coexisting twin live fetus (CHMTF): the uncommon diagnostic enigma—simplified

Abstract Background Twin pregnancy comprising of a complete hydatidiform mole with a coexisting twin live fetus is an uncommon condition with an incidence rate of 1 in 20,000 to 1 in 100,000 pregnancies, more so in assisted reproductive technologies. The primary diagnosis is made on ultrasound and adjunct fetal MRI helps in unequivocally differentiating it from other disorder. Case presentation We present a case report of a twin pregnancy consisting of complete hydatidiform mole with a coexisting twin live fetus in a 27-year-old primigravida conception, primarily focusing on its diagnostic algorithm and related clinical aspects, adding to the paucity of existing literature. Conclusions Following the correct diagnostic algorithm with imaging studies like USG and more importantly MRI, combined with the bioclinical picture helps in reaching the accurate diagnosis.

A comparison of the clinical features of molar pregnancy in adolescents and adults

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.
 doi: https://doi.org/10.12669/pjms.40.5.8383
 How to cite this: Ozer M, Ozer PT, Karaca I, Karaca S, Ileri A, Budak A. A comparison of the clinical features of molar pregnancy in adolescents and adults. Pak J Med Sci. 2024;40(5):---------. doi: https://doi.org/10.12669/pjms.40.5.8383
 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

31. Complex Care in an Adolescent: Management of Molar Pregnancy, Malignancy, Maternal Complications, and Malformations

31. Complex Care in an Adolescent: Management of Molar Pregnancy, Malignancy, Maternal Complications, and Malformations

Twin pregnancy with one alive and co-existing complete mole

Twin pregnancy with one alive and co-existing complete mole

Post molar choriocarcinoma with solitary renal metastasis in the absence of primary uterine tumor: a case report and review of the literature

BackgroundChoriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage.Case presentationA 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis.ConclusionsUrological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole.

Morphology combined with HER2 D-DISH ploidy analysis to diagnose partial hydatidiform mole: an evaluation audit using molecular genotyping

AimsA hydatidiform mole (HM) is classified as complete (CHM) or partial (PHM) based on its morphology and genomic composition. Ancillary techniques are often required to confirm a morphologically suspected PHM...

Novel scoring system provides high separation of diploidy and triploidy to aid partial hydatidiform mole diagnosis: an adaption of HER2 D-DISH for ploidy analysis

AimsDiagnosis of hydatidiform mole or molar pregnancy based on morphology alone can be challenging, particularly in early gestation, necessitating the use of ancillary techniques for accurate diagnosis. We sought to...

A Case Report of a Rare Cause of Diagnostic Dilemma in the Management of Gestational Choriocarcinoma

Choriocarcinoma belongs to one extreme of molar pregnancy, the other end is hydatidiform mole. It is a fast-growing tumor that occurs in a woman’s uterus but can easily metastasize to the lungs, liver, and brain. The abnormal tumor cells start in the tissue that would normally become the placenta. Choriocarcinoma developed after a normal pregnancy in 1 in 50,000, miscarriages in 1 in 15,000, and complete mole 1 in 40. The tumor may mimic uterine fibroid, especially when it presents as a uterine mass (which is not the common presentation) posing an initial diagnostic dilemma, as seen in our patient. The patient was an 18years P0+1 whose last normal menstrual period was a year before presentation. She presented with a history of loss of 14-week conception, then followed by 11months history of abnormal scanty vaginal bleeding lasting 21-27 days monthly, the patient was found to be mildly pale but had stable vital signs, she had a uterine mass of about 22weeks size, abdominal ultrasound scan revealed uterine fibroid. In the process of investigation serum pregnancy test was done and was found to be positive, with markedly elevated serum beta hcg. We made an assessment of choriocarcinoma and we commenced her on chemotherapy, she received 4 courses but with no decline in beta HCG. She had a total abdominal hysterectomy and histology confirmed choriocarcinoma, serum beta HCG was then immediately noticed to decline, she had further chemotherapy, and the patient did well subsequently. Huge choriocarcinoma may be mistaken for uterine fibroid, hence a high index of suspicion for choriocarcinoma is important if a patient presents with a recent history of miscarriage, uterine mass, vaginal bleeding, and a positive pregnancy test.

Trans-Abdominal Ultrasonographic Evaluation of Molar Pregnancy

Background: Molar pregnancy is the most common benign from of gestational trophoblastic neoplasm. Molar pregnancy has distinction histologic characteristics a custic or grape like degeneration of chorionic villi, absent or inadequate vascularization of chorionic villi and abnormal proliferation of placental trophoblast. Objective: To assess the role of ultrasonography (UCG) in the evaluation of molar pregnancy. Method: This cross sectional study was carried out on consecutively selected 40 patient out of 45 patient who were suspected to suffering from molar pregnancy. This study was take place Mymensingh Medical College Hospital from those who were attended the department for ultrasonography for suspicious features of gestational trophoblastic diseases. Result: Among the 40 patients in this study 9 were 15-20 years of age, total 24 were between 20-35 years of age and 7 patients were 35-45 years of age. The range of age was 15 to 45 years. Conclusion: In conclusion ultrasonography can be accepted as an initial imaging modality in the evaluation of gestational trophoblastic diseases.

Exceptional Case of Spontaneous Ovarian Hyperstimulation Syndrome in Complete Molar Pregnancy: A Case Study

Spontaneous ovarian hyperstimulation syndrome (OHS) is an uncommon condition. We report the case of a 38-year-old woman admitted to the emergency department with vaginal bleeding, pelvic pain, and an extraordinarily high human chorionic gonadotropin (hCG) level of 1,000,000 mIU/mL. Uterine aspiration confirmed a complete hydatidiform mole. Ten days post-discharge, she returned, exhibiting severe abdominal pain, vomiting, an hCG level of 46,769 mIU/mL, and ultrasound evidence of theca lutein cysts (right ovary: 1329 cm³; left ovary: 500 cm³) along with ascites. Suspected of having OHS, she was hospitalized for clinical management. Treatment included intravenous hydration, analgesia, thromboprophylaxis, and daily laboratory tests, leading to symptomatic improvement despite rising hCG levels. After a 35-day hospital stay, she commenced chemotherapy at a specialized cancer hospital. This case emphasizes the importance of healthcare professionals being alert and aware of the possibility of this diagnostic suspicion in such cases, particularly highlighting the need for hospitalization in moderate to severe instances.

Aneuploidy is frequent in heterozygous diploid and triploid hydatidiform moles

Hydatidiform moles are abnormal conceptuses. Many hydatidiform moles are diploid androgenetic, and of these, most are homozygous in all loci. Additionally, most hydatidiform moles are euploid. Using Single Nucleotide Polymorphism (SNP) array analysis, in two studies a higher frequency of aneuploidy was observed in diploid androgenetic heterozygous conceptuses, than in their homozygous counterparts. In the Danish Mole Project, we analyze conceptuses suspected to be hydatidiform moles due to the clinical presentation, using karyotyping and Short Tandem Repeat (STR) analysis. Among 278 diploid androgenetic conceptuses, 226 were homozygous in all loci and 52 (18.7%) were heterozygous in several loci. Among 142 triploid diandric conceptuses, 141 were heterozygous for paternally inherited alleles in several loci. Here we show that the frequencies of aneuploidy in diploid androgenetic heterozygous and triploid diandric heterozygous conceptuses were significantly higher than the frequency of aneuploidy in diploid androgenetic homozygous conceptuses. In diploid androgenetic and triploid diandric conceptuses that are heterozygous for paternally inherited alleles, the two paternally inherited sets of genomes originate in two spermatozoa. Each spermatozoon provides one pair of centrioles to the zygote. The presence of two pairs of centrioles may cause an increased risk of aneuploidy.

Kenneth Dawson Bagshawe. 17 August 1925—27 December 2022

Kenneth Bagshawe was a physician, a scientist and an architect of modern oncology. He was first to show that combination chemotherapy can cure a non-haematological cancer, choriocarcinoma. He demonstrated how a tumour marker in blood and urine can give a quantitative representation of the total amount of tumour, providing a monitor of response to treatment or relapse and an indicator of prognosis. He enhanced understanding and treatment of gestational trophoblastic diseases (GTD), a group of which choriocarcinoma is the most lethal member. The most common form of GTD is hydatidiform mole and he developed a national system for management, resulting in a cure rate of virtually 100%. For choriocarcinoma, the figure is today approaching 98%. His system is used in many countries, and over several decades has contributed to the cure and preservation of fertility in hundreds of thousands of women who previously had little or no hope. He used the same principles to treat testicular and ovarian germ cell tumours, again achieving high levels of cure in patients whose disease had spread and would previously have been fatal. He innovated throughout his career, seeking improved tumour specificity in diagnosis and treatment of GTD and inventing antibody-directed enzyme prodrug therapy for more common cancers. He founded the first department of oncology in the UK and devoted much time to developing the speciality, directing research funding organizations and supporting the development of the speciality worldwide. He was a dedicated, original and hugely productive pioneer of oncology.

Study of vesicular mole and its outcomes

Vesicular mole is defined as the premalignant form of gestational trophoblasticneoplasia. I5-20% of complete moles and <5% of partial moles will develop into Gestational Trophoblastic Neoplasia. It is of clinical and epidemiological interest because of its potential for significant consequences on women's health. The study aims to determine the incidence, outcomes and complications of pregnancy with vesicular mole at SKNMC hospital, Pune. It was a retrospective study. Approval for the study was obtained from institutional ethical committee. Data was collected from OPD, OT register and Indoor patient record file from August 2015 to August 2020. Proformas were filled. All the collected data was compiled in a master chart, analysed and outcomes of different variables under study have been expressed in the form of mean, frequencies, percentages and charts. The incidence of molar pregnancy was 0.17% or 1 in 561 deliveries. Vesicular mole occurred more in the age group 16 to 25 years, was lowest in age group 31-35yrs. Vesicular mole was most common in nulliparous women. The mean gestational age of the patients at presentation was 9.4 week. Hemorrhage after suction and evacuation was seen in 26% cases needing intra and post-operative blood transfusion. 6% of patients developed thyrotoxicosis. During follow up invasive mole was diagnosed in 2 cases (6%). The case fatality rate is 2.9% in our study. 1 patient (3%) developed choriocarcinoma and died within 6months after hysterectomy and chemotherapy. The incidence of 1 in 561 deliveries which is higher than non-Asian countries 1/752 but lower than other Asian countries 1/387. The routine first trimester ultrasonography helps in early detection of asymptomatic women. If not followed up regularly it can be life threatening.

Factors influencing decision-making for the anesthetic technique in molar pregnancy patients for suction curettage: A retrospective study

Anesthetic techniques for suction curettage in molar pregnancy patients described in the literature can be classed into general anesthesia and regional anesthesia techniques. The aim of the present study was to report the factors influencing the decision-making for the choice of anesthetic technique in molar pregnancy patients who underwent suction curettage at Siriraj Hospital. The reported intraoperative and postoperative complications were also analyzed.A retrospective chart review was conducted among pregnant women diagnosed with molar pregnancy who had underwent suction curettage under anesthesia at Siriraj Hospital between January 2007 to September 2021. Overall, 244 patients were diagnosed with molar pregnancy, with 110 of these included for analysis in this study after consideration of the inclusion and exclusion criteria. Quantitative data of the included patients were analyzed by either unpaired t-test or Mann–Whitney U test, while qualitative data were analyzed by the chi-square test. Logistic regression was used to establish the factors influencing the decision-making for the anesthetic technique.General anesthesia was the most preferred anesthetic technique (77.4%) in the molar pregnancy patients who had underwent suction curettage, followed by regional anesthesia (11.3%) and intravenous sedation (11.3%). General anesthesia was likely to be used in patients with an enlarged uterine size ≥ 16 weeks with an adjusted odds ratio of 11.64 (95% CI 1.08–125.72, p < 0.05). Patients with a larger uterine size were associated with higher beta-hCG levels, resulting in more severe medical complications, such as hyperthyroidism and hyperemesis gravidarum (p < 0.05). Intraoperative complications, such as uterine atony (17.7%), massive hemorrhage (7.3%), and pulmonary edema (4.2%), were confined within patients receiving general anesthesia, but there was no statistical significance. None of the patients had anesthesia-related complications. The reported postoperative serious complications, such as pulmonary edema (4.2%), which required postoperative intubation and transferal to the intensive care unit, were all in the general anesthesia group. Patients with higher co-morbidities were advised by anesthesiologists to receive general anesthesia. However, an enlarged uterine size ≥ 16 weeks was the only factor that had an influence on the decisions of the anesthesiologists to provide general anesthesia.

ST-segment elevation in chronic bleeding post-curettage with COVID-19 antibodies: A case report

Acute coronary syndrome has a variety of symptoms and remains poorly under diagnosed and under treatment in women, especially myocardial infarction or ischaemic with non-obstructive coronary arteries (INOCA) as the culprit. We present a case of an Indonesian adult female with hypoxemia and ST-elevation in post-curettage due to molar pregnancy and positive COVID-19 antibodies.A 43-year-old Indonesian female was admitted due to confusion, dyspnoea, and chronic bleeding after the curettage. The electrocardiogram (ECG) showed ST-elevation in lead I and aVL. Her condition quickly stabilised after getting oxygen supplementation and nitro-glycerine with ST-elevation resolution and no neurological impairments. Due to COVID-19 pandemic, she was checked for a swab test which showed negative but positive on her antibodies test. Chest X-ray was normal, but the echocardiography showed mild left atrial dilatation. After standard atherosclerosis treatment and anticoagulant, her condition improved, despite recurring vaginal bleeding. During her outpatient follow-ups, suspected intrauterine leiomyoma was diagnosed by ultrasound. Cytokines and inflammatory responses from prolonged bleeding, hormones, metabolic disturbances, and post-COVID-19 infection have the potential to provoke INOCA. Considering the complexity of our case, contributing factors to INOCA must be addressed to optimise the strategy. Further, imaging tests should be done to confirm the diagnosis.

N-linked α2,6-sialylation of integrin β1 by the sialyltransferase ST6Gal1 promotes cell proliferation and stemness in gestational trophoblastic disease

IntroductionGestational trophoblastic disease (GTD) encompasses a spectrum of rare pre-malignant and malignant entities originating from trophoblastic tissue, including partial hydatidiform mole, complete hydatidiform mole and choriocarcinoma. β-galactoside α2,6 sialyltransferase 1 (ST6Gal1), the primary sialyltransferase responsible for the addition of α2,6 sialic acids, is strongly associated with the occurrence and development of several tumor types. However, the role of ST6Gal1/α2,6 -sialylation of trophoblast cells in GTD is still not well understood. MethodsThe expression of ST6Gal1 was investigated in GTD and human immortalized trophoblastic HTR-8/SVneo cells and human gestational choriocarcinoma JAR cells. We evaluated the effect of ST6Gal1 on proliferation and stemness of trophoblastic cells. We also examined the effect of internal miR-199a-5p on ST6Gal1 expression. The role of ST6Gal1 in regulating α2,6-sialylated integrin β1 and its significance in the activation of integrin β1/focal adhesion kinase (FAK) signaling pathway were also explored. ResultsST6Gal1 was observed to be highly expressed in GTD. Overexpression of ST6Gal1 promoted the proliferation and stemness of HTR-8/SVneo cells, whereas knockdown of ST6Gal1 suppressed the viability and stemness of JAR cells. MiR-199a-5p targeted and inhibited the expression of ST6Gal1 in trophoblastic cells. In addition, we revealed integrin β1 was highly α2,6-sialylated in JAR cells. Inhibition of ST6Gal1 reduced α2,6-sialylation on integrin β1 and suppressed the integrin β1/FAK pathway in JAR cells, thereby affecting its biological functions. DiscussionThis study demonstrated that ST6Gal1 plays important roles in promoting proliferation and stemness through the integrin β1 signaling pathway in GTD. Therefore, ST6Gal1 may have a potential role in the occurrence and development of GTD.

Comparative Investigation of Color Doppler Ultrasonography Parameters of the Uterine Artery in Patients with Post-molar GTN and Patients Recovered from Molar Pregnancy and its Role in Predicting the Probability of Occurrence

Objectives: Hydatiform mole can progress to gestational trophoblastic neoplasia (GTN), and we are looking for non-invasive methods to predict it. Old age, higher serum BHCG levels, and expression of genes, such as VEGF-EG, HIF-1α, and TGF-ß are known as predictive factors. We performed this study to evaluate the role of bilateral uterine artery doppler ultrasound in predicting postmolar- GTN. Methods: In this prospective cohort study, 42 patients with complete molar pregnancy were examined. Inclusion criteria confirmed molar pregnancy by histopathological examination. Exclusion criteria were patients more than 40 years old, patients with completed family childbearing planning, and diagnosis of GTN during the routine histopathological study. Before molar evacuation and four weeks later, bilateral uterine artery doppler sonography to determine the PI, RI, and PSV was performed. Serum BHCG levels were also measured before molar evacuation and weekly after evacuation until it exhibited spontaneous remission or developed GTN. Results: About 36 patients were cured, and six others developed post-molar GTN. The bilateral uterine artery doppler sonography between the two groups showed a lower UA RI in the post-molar-GTN group before evacuation (P=0.048). Data demonstrated significant increases in Right.UA.RI (P=0/008), Left.UA.PI (P=0/037), and Right.UA.PSV (P=0/024) in the spontaneous remission group during 28 days follow-up period. There were no significant differences in these parameters in the GTN group throughout the time of follow-up. Conclusion: It seems that Doppler ultrasound plays a role in predicting GTN following uterine evacuation. A lower resistance in the uterine artery before evacuation and the remaining uterine artery blood flow constant after evacuation is associated with the development of post-molar- GTN.

Gestational trophoblastic neoplasia with pulmonary embolism mimicking tuberculosis

ABSTRACT Gestational trophoblastic neoplasia (GTN) comprises a group of human neoplastic diseases that derive from fetal trophoblastic tissues. They are proliferative as well as degenerative disorders of placental elements and include complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) (90%), invasive mole (IM) (5–8%), which could also be metastatic, villous, or villous choriocarcinoma (CC) (1–2%), and placental site trophoblastic tumor (PSTT) (1–2%). We present three cases of GTN, two mimicking tuberculosis radiologically, and all three are associated with pulmonary embolism.