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OBJECTIVE: Our study aims to determine the frequency and types of GTD (Gestational Trophoblastic Disease) in our clinic, to evaluate its relationship with clinical parameters, and the consistency of clinical prediagnosis and pathological definitive diagnosis. PATIENTS AND METHODS: In the present study, hospital records of 120 patients with gestational trophoblastic disease between January 2019 and August 2022 were obtained and evaluated retrospectively. Demographic, hematological, biochemical, and clinical data were collected in detail, and the data were analyzed statistically. RESULTS: Our study included a total of 120 female patients, with an average age of 31.16±9.70. The average number of patients was 3. The average time for women to receive the diagnosis was 9.80±2.45 weeks, with the most frequent complaint on our part being bleeding (85.8%). When the pathology outcomes of the patients we included in our study were examined, it was found that the number of patients diagnosed with incomplete abortion was 34, the number of patients diagnosed with complete abortion was 82, the number of invasive moles diagnosed was 3, and the number of patient diagnosed with choriocarcinoma was 1. Kappa ratio was calculated as 0.419 (p<0.001) when the compliance of the clinical diagnosis was assessed. This value was consistent with median level alignment. In a study that examined the three years of our calism in our bulk, 1.8 per 1,000 births were followed frequently. CONCLUSIONS: We should inform patients in detail about gestational trophoblastic diseases and warn patients not to delay their consequences. We should recommend that pregnancy be avoided for 12 months for low-risk patients and 18 months for high-risk patients after GTD. [ABSTRACT FROM AUTHOR]

Intraplacental choriocarcinoma is a rare tumour, with approximately 62 reported cases. It may manifest as a spectrum of disease ranging from an incidental lesion diagnosed on routine placental examination to disseminated maternal and/or neonatal disease. In this case series, we presented two rare cases of intraplacental choriocarcinoma with extremely varied clinical presentations. The extremely varied clinical presentations of both patients described in the case series complicated the process of arriving at the diagnosis. In both cases, subsequent investigations showed no maternal or neonatal metastasis, and maternal serum beta-hCG levels downtrended with conservative management. We aim to highlight the importance of performing a detailed physical examination and evaluation of the patient and multidisciplinary management with oncology opinion. A detailed examination of the placenta should also be considered when faced with obstetric complications so that early diagnosis and the required management can be executed in a prompt fashion. [ABSTRACT FROM AUTHOR]

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Identifying hydatidiform moles (HMs) is crucial due to the risk of gestational trophoblastic neoplasia. When a HM is suspected on clinical findings, surgical termination is recommended. However, in a substantial fraction of the cases, the conceptus is actually a non-molar miscarriage. If distinction between molar and non-molar gestations could be obtained before termination, surgical intervention could be minimized. Circulating gestational trophoblasts (cGTs) were isolated from blood from 15 consecutive women suspected of molar pregnancies in gestational week 6–13. The trophoblasts were individually sorted using fluorescence activated cell sorting. STR analysis targeting 24 loci was performed on DNA isolated from maternal and paternal leukocytes, chorionic villi, cGTs, and cfDNA. With a gestational age above 10 weeks, cGTs were isolated in 87% of the cases. Two androgenetic HMs, three triploid diandric HMs, and six conceptuses with diploid biparental genome were diagnosed using cGTs. The STR profiles in cGTs were identical to the profiles in DNA from chorionic villi. Eight of the 15 women suspected to have a HM prior to termination had a conceptus with a diploid biparental genome, and thus most likely a non-molar miscarriage. Genetic analysis of cGTs is superior to identify HMs, compared to analysis of cfDNA, as it is not hampered by the presence of maternal DNA. cGTs provide information about the full genome in single cells, facilitating estimation of ploidy. This may be a step towards differentiating HMs from non-HMs before termination. • Ploidy in hydatidiform moles can be determined by a liquid biopsy. • Circulating trophoblasts from hydatidiform moles can be isolated from blood. • Circulating trophoblasts enable diagnosis of androgenetic and triploid moles. [ABSTRACT FROM AUTHOR]

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]

Hydatidiform moles are the most common type of gestational trophoblastic disease. Internationally the incidence of hydatidiform moles is 1–2:1000 pregnancies. Early detection of women with hydatidiform moles is preferential, as these women are at a higher risk of developing other gestational trophoblastic disease. Despite Ultrasound being the most common modality used to diagnose hydatidiform moles, its diagnostic value and accuracy throughout all trimesters remains uncertain. Thus, the aim of this review was to explore and evaluate the diagnostic value and accuracy of Ultrasound in diagnosing hydatidiform mole throughout all trimesters of pregnancy. The databases MEDLINE and CINAHL were searched between 2004 and 2021. Included studies were quality assessed using the Mixed Methods Appraisal Tool. A total of 8 studies were included. The narrative synthesis identified four themes: Misdiagnosis, Complete and Partial molar pregnancy, Operator dependency and Gestational age. The meta-analysis highlighted although the sensitivity of ultrasound for diagnosing hydatidiform moles is relatively low at 52.2%, the specificity was high at 92.6%. While histological examination remains the gold standard for detecting hydatidiform moles, our review made evident that ultrasound is a beneficial diagnostic tool in the detection of Hydatidiform moles, especially alongside other diagnostic investigations. This review has highlighted and collated the main barriers and facilitators to diagnosing hydatidiform moles using ultrasound. Findings suggest that although sonographic detection of hydatidiform moles remains a diagnostic challenge, seeking a second opinion or repeating scans before making a final diagnosis should be embedded into clinical practice. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to determine whether or not there was a relationship between complete hydatidiform mole (CHM) and serum Vitamin D level by comparing CHM patients with two control groups and to determine whether or not Vitamin D deficiency is a risk factor for CHM. PATIENTS AND METHODS: This prospective study included 30 patients diagnosed with CHM (case group), 30 patients in the first trimester of a healthy pregnancy (control group), and 30 healthy non-pregnant subjects (control group). A record was made of serum 25-hydroxyvitamin D (25-OH D vitamin) levels, age, body mass index (BMI), gravida, parity, and the number of abortus. The serum 25-OH D vitamin levels were examined in each group and compared between groups. RESULTS: The 25-OH D vitamin level of all the patients in the study was determined as 11.16±8.64 ng/mL. No significant difference was determined between the groups in respect of 25 OH-D vitamin levels. When comparisons were made between the four subgroups according to the 25-OH-D level, no significant difference was determined between the CHM and control groups. When the patients were separated as obese and non-obese groups, no significant difference was determined between the groups. CONCLUSIONS: Severe deficiency, deficiency, or insufficient levels of serum Vitamin D are not thought to be risk factors for CHM patients. [ABSTRACT FROM AUTHOR]

Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention. [ABSTRACT FROM AUTHOR]

Study Objective: To demonstrate laparoscopic management of a molar scar ectopic pregnancy.Design: Stepwise demonstration of the technique with narrated video footage.Setting: Cesarean scar ectopic pregnancy and molar pregnancy are 2 separate extremely rare pathologies with an incidence range from 1/1800 to 1/2500 of all pregnancies for the former [1,2]. The concurrence of both cesarean scar ectopic and molar pregnancy is furthermore exceptionally rare, and there are only 8 reported cases of cesarean scar molar pregnancy in literature till date [3]. There is a high risk of uterine rupture, uncontrolled hemorrhage, hysterectomy, and significant maternal morbidity owing to thin myometrium and fibrous scar after cesarean section [4,5]. Knowledge and awareness about this clinical condition aid in early diagnosis and reduced morbidity. Here, we present a rare case of cesarean scar ectopic pregnancy that was operated for failed medical management and diagnosed to be molar scar ectopic pregnancy intraoperatively.Interventions: Total laparoscopic approach to molar scar ectopic pregnancy excision involved the following steps, strategies to minimize blood loss, and complete enucleation of tissue: (1) Hysteroscopy to localize the scar ectopic and its type and size (2) Bladder dissection to expose scar (3) Intramyometrial injection of vasopressin (4) Use of harmonic scalpel to delineate the gestational sac (5) Complete evacuation of products of conception (6) Excision of scar tissue (7) Uterine repair in 2 layers CONCLUSION: There are only 8 reported cases of cesarean scar molar pregnancy in literature till date, and all patients had at least 2 previous uterine curettages with abnormally increased β-hCG levels. The clinical manifestations were varied, the most common symptom being vaginal bleeding for a period >1 month, including our case [3]. Considering the limitations of ultrasound, magnetic resonance imaging, and serum hCG levels in the differential diagnosis of molar cesarean scar pregnancy from normal cesarean scar pregnancy, postoperative specimen should be sent for histologic examination [6]. As seen in our case, the possibility of molar pregnancy at cesarean scar ectopic site should be kept in mind in cases with rising β-hCG levels despite continuous medical interventions, which was being medically managed for 3 months. Our case is the first to be successfully managed with laparoscopic surgery as the previously reported cases were managed with suction evacuation, chemotherapy, laparotomy, or hysterectomy [3]. [ABSTRACT FROM AUTHOR]

Molar pregnancy is a gestational trophoblastic disease characterized by an abnormal growth of placental tissues because of a nonviable pregnancy. The understanding of the pathophysiology and management of molar pregnancy has significantly increased in the recent years. This study aims to determine the characteristics and trends of published articles in the field of molar pregnancy through a bibliometric analysis. Using the Scopus database, we identified all original research articles on molar pregnancy from 1970 to 2020. Bibliographic and citation information were obtained, and visualization of collaboration networks of countries and keywords related to molar pregnancy was conducted using VOSviewer software. We obtained a total of 2009 relevant papers published between 1970 and 2020 from 80 different countries. The number of publications continued to increase through the years. However, the number of publications in molar pregnancy is still low compared to the other research fields in obstetrics and gynecology. The USA (n = 421, 32.1%), Japan (n = 199, 15.2%), and the UK (n = 191, 14.6%) contributed the greatest number of publications in this field. The top journals which contributed to the field of molar pregnancy include AJOG (n = 91), Obstetrics and Gynecology (n = 81), and the Gynecologic Oncology (n = 57). The most cited articles in molar pregnancy include papers on the genetics and chromosomal abnormalities in molar pregnancies. The focus of current research in this field was on elucidating the molecular mechanism of hydatidiform moles. Our bibliometric analysis showed the global research landscape, trends and development, scientific impact, and collaboration among researchers in the field of molar pregnancy. [ABSTRACT FROM AUTHOR]

Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27–46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels <10 multiples of the median were significantly more likely to reach 24 weeks' gestation compared with those with free beta human chorionic gonadotropin levels >10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3–36.5; P =.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P =.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19–34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study. [ABSTRACT FROM AUTHOR]

A healthy pregnancy requires the development of maternal-fetal immune tolerance against the semi-allogeneic fetus. The interactions between the trophoblastic cells and the maternal immune cells (p.e., natural killer cells, T cells, macrophages, dendritic cells and B-cells) are important for the development of the maternal-fetal immune tolerance and the placental growth and function. These interactions are mediated by cell to cell contact and secreted molecules such as cytokines, chemokines, angiogenic factors and growth factors. The maternal immune cells are present in normal non-pregnant and pregnant endometrium and there are several lines of evidence based on immunohistochemical and RNA sequencing data that the decidual immune cells and immune-related pathways display alterations in GTD, which may have pathogenetic and clinical significance. The present review focuses on the usefulness of the immunohistochemical analysis which provides multiparametric in situ information regarding the numbers, the immunophenotypes and the immunotopographical distributions of the decidual immune cells in tissue sections from normal pregnancy and GTD. We also discuss the significance of the immunohistochemical information in order to gain insight in the putative mechanisms explaining the alterations of the decidual immune cells in GTD and the potential implications of these alterations in the pathogenesis and the clinical behavior of GTD. [ABSTRACT FROM AUTHOR]

Background: There are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients with this rare disease. Primary Objectives and Study Hypothesis: TITANIUM is a prospective, multicenter, observational study aiming to describe ultrasound features of gestational trophoblastic neoplasia and to investigate the role of ultrasound in identifying patients at high risk of resistance to single-drug therapy. The study hypothesis is that ultrasound could improve the International Federation of Gynecology and Obstetrics (FIGO) scoring system for early identification of patients predisposed to single-drug resistance. Trial Design and Major Inclusion/Exclusion Criteria: Patients eligible have a diagnosis of gestational trophoblastic neoplasia according to FIGO or the criteria set by Charing Cross Hospital, London, UK. At diagnosis, patients are classified as low-risk (score 0–6) or high-risk (score >6) according to the FIGO risk scoring system, and a baseline ultrasound scan is performed. Patients receive treatment according to local protocol at each institution. Follow-up ultrasound examinations are performed at 1, 4, 10, 16, and 22 months after start of chemotherapy, and at each scan, serum human chorionic gonadotropin (hCG) level, and chemotherapy treatment, if any, are recorded. Primary Endpoints: Our aims are to define ultrasound features of gestational trophoblastic neoplasia and to develop a predictive model of resistance to single-drug therapy in low-risk patients. Sample Size: The sample size was calculated assuming that 70% of patients with gestational trophoblastic neoplasia are at low risk, and estimating the rate of resistance to single-drug therapy in this group to be 40%. Assuming a dropout rate of 10%, we should recruit at least 120 patients. With this sample size, we can attempt to create a mathematical model with three variables (either two ultrasound parameters in addition to the risk score or three ultrasound variables statistically significant at univariate analysis) to predict resistance to single-drug therapy in low-risk patients. Estimated Dates for Completing Accrual and Presenting Results: The accrual started in February 2019. Additional referral centers for gestational trophoblastic disease, with similar ultrasound expertise, are welcome to participate in the study. Enrollment should be completed by December 2021, and analysis will be conducted in December 2023. Trial Registration: The study received the Ethical Committee approval of the Coordinator Center (Rome) in January 2019 (Protocol No. 0004668/19). [ABSTRACT FROM AUTHOR]

Introduction: Protein expression in cells are associated with oncogenesis. This study aims to explore proteomic profiles and discover potential biomarkers that can predict malignant transformation of hydatidiform mole.Methods: Retrospective analysis was done in 14 cases of remission hydatidiform mole and 14 cases of hydatidiform mole who later developed malignancy (GTN group). Molar tissues were retrieved from -70 °C frozen tissue. Subsequently, a large-scale proteomic analysis was performed to identify proteins and compare their abundance levels in the preserved molar tissues from these two groups using a dimethyl-labeling technique coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS).Results: A total of 2,153 proteins were identified from all samples. 22 and 10 proteins were significantly up-regulated and down-regulated, respectively, in the GTN group compared with the mole group. These altered proteins were found in several biological groups such as cell-cell adhesion, secreted proteins, and ribonucleoproteins. Several hormone-related proteins were among the most up-regulated proteins in the GTN group including choriogonadotropin subunit beta (β-hCG) and alpha (α-hCG), growth/differentiation factor 15, as well as both pregnancy-specific beta-1-glycoproteins 2 and 3. In contrast, protein S100-A11 and l-lactate dehydrogenase A chain, were down-regulated in molar tissue from most patients in the GTN group.Discussion: This study identified a set of differentially expressed proteins in molar tissues that could potentially be further examined as predictive biomarkers for the malignant transformation of CHMs. A molar proteome database was constructed and can be accessible online at http://sysbio.chula.ac.th/Database/GTD_DB/Supplementary_Data.xlsx. [ABSTRACT FROM AUTHOR]

Abstract Distinction of hydatidiform moles from non-molar specimens and sub-classification of hydatidiform moles as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Diagnosis based on morphology is subject to interobserver variability. The unique genetics of CHMs, PHMs, and non-molar specimens allow for certain techniques, including immunohistochemical analysis of p57 expression and PCR-based DNA genotyping, to refine diagnosis. p57 immunostaining identifies CHMs, which lack p57 expression due to lack of maternal DNA, but does not distinguish PHMs from non-molar specimens since both express p57 due to the presence of maternal DNA. Genotyping distinguishes purely androgenetic CHMs from diandric triploid PHMs and both of these from biparental non-molar specimens by comparing villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles. An algorithmic approach using these ancillary techniques is advocated. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Objective: The aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting. Methods: The prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs. Results: Among 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test). Conclusions: Under the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN. [ABSTRACT FROM AUTHOR]

We evaluated the accuracy of the ultrasound signs suggestive of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) in a cohort of women with histologically confirmed hydatidiform mole (HM) who presented with early pregnancy failure, including 103 CHM and 95 PHM for which ultrasound images were available. The accuracy of the differential diagnosis was significantly (p < 0.001) greater during secondary examination of ultrasound images compared with the original primary ultrasound examination. The interobserver agreement analysis indicated only a fair to moderate agreement between the two examinations (kappa value 0.41; 95% CI 0.29-0.53). Most HM present as early pregnancy failure and identification of early ultrasound signs can improve the differential diagnosis between CHM and PHM. [ABSTRACT FROM AUTHOR]

A 47-yr-old multiparous female bonobo (Pan paniscus) tested positive for pregnancy on a routine urine test. Because this geriatric animal was considered postreproductive, oral contraception had been discontinued. Sequential transabdominal ultrasound evaluations were performed under voluntary behavior and revealed that the uterus contained a mass of heterogenous tissue which was rapidly increasing in size. Due to a lack of normal fetal development and the ultrasonographic appearance of the uterine tissue, a molar pregnancy was suspected. Ovariohysterectomy was performed, and a complete hydatidiform mole was confirmed through human chorionic gonadotropin levels as well as gross and histological examination of the uterus. To the authors' knowledge, this is the first time a complete molar pregnancy has been reported antemortem in a nonhuman great ape, although a single case of partial hydatidiform mole was previously documented in a chimpanzee on postmortem examination. This case describes the successful medical and surgical management of complete molar pregnancy in a bonobo and provides support for extending the age range of birth control recommendations in geriatric captive great apes that exhibit active breeding behavior. [ABSTRACT FROM AUTHOR]

Introduction: Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast actions. We hypothesized that the localization and expression patterns of LIF and IGF-1 in partial and complete hydatidiform moles (HM) compared with normal first trimester placentas may provide an understanding of the proliferative processes in HMs.Methods: The study population included curettage material of women diagnosed as complete or partial HM as a result of histopathological and immunohistochemical examination (complete HM group, n = 8; partial HM group, n = 8) and women undergoing dilatation&curettage for unwanted pregnancies (control group, n = 8). Expression of LIF and IGF-1 among placental cell groups was evaluated immunohistochemically and given a score depending on immunostaining intensity.Results: In normal chorionic villi strong expression of LIF and IGF-1 was present. Both LIF and IGF-1 expressions were weaker in the chorionic villi of complete HMs. In complete mole decidua there was a significant decrease in glandular and endothelial IGF-1 expression along with a decrease in decidual cell LIF expression compared to normal first trimester decidua. LIF expression in extravillous trophoblasts was stronger in complete molar placentas compared to normal placentas.Discussion: LIF and IGF-1 are important regulators of trophoblast proliferation and invasion. Differential expression of LIF and IGF-1 in molar trophoblasts and chorionic villi might have a role in regulation of trophoblasts in complete moles. Decreased expression of glandular IGF-1 and decidual LIF might be related to the decidual changes during trophoblastic proliferation and invasion of decidua in complete HMs. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the characteristics and outcomes of patients treated for gestational trophoblastic neoplasia (GTN) with second-line 5-day dactinomycin after failed first-line 8-day methotrexate. Methods: From 1999 to 2017, patients with methotrexate resistant GTN treated with second line dactinomycin were identified at the French Trophoblastic Disease Reference Center. Using univariate and multivariate analysis, we identified significant predictive factors of second line dactinomycin failure. Results: A total of 877 GTN patients were treated with first-line 8-day methotrexate, of which 103 required second-line 5-day dactinomycin for methotrexate failure. Complete response was observed in 78 patients (75.7% [95% confidence interval, 66.3–83.6]; P < 0.0001), whereas 25 needed third-line treatment, 13 for dactinomycin resistance and 12 for post–dactinomycin relapse. Overall survival of patients treated with dactinomycin was 100%. An interval of greater than or equal to 7 months between antecedent pregnancy termination and methotrexate initiation was a predictive factor significantly associated with second-line dactinomycin failure in multivariate analysis (exact odds ratio, 9.17 [95% confidence interval, 1.98–50.70]; P = 0.0029). No grades 4 and 5 adverse effects were experienced and the most common toxicity being grade 1 nausea (14.6%). Conclusion: Given a 75.7% complete response rate in methotrexate failed low-risk GTN patients treated with second-line dactinomycin and an overall survival rate of 100% after third-line treatment, the use of dactinomycin should be favored as second-line, regardless of human chorionic gonadotropin level at the time of dactinomycin initiation. However, an interval between the termination of the antecedent pregnancy and methotrexate initiation longer than 6 months should encourage considering alternative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: The majority of complete hydatidiform moles (CHM) are detected on ultrasound examination by the end of the first trimester when they present as multiple sonolucent cysts. To better understand the pathophysiology of this unique placental pathology and improve its prenatal diagnosis and management we have reviewed the ultrasound features of CHM before the appearance of cystic changes.Study Design: We searched our database to identify all women diagnosed with a complete hydatidiform mole confirmed by histopathology who had an ultrasound examination before 9 weeks' gestation. We reviewed their ultrasound reports and all the corresponding images.Results: The study group included 39 women with a positive pregnancy test and vaginal bleeding, 36 of whom had at least two ultrasound examinations before 9 weeks' gestation. At the first scan (mean gestation age 7 + 1 weeks; SD 1.1), 29 out 39 (74.4%) of CHM presented as a heterogeneous hyperechogenic mass with or without gestational sac and the remaining ten (25.6%) cases as a regular 4-week gestational sac. Cystic molar changes became apparent from the end of the second month of gestation.Conclusion: The development of a CHM follows a well-defined pattern starting with a macroscopically normal gestation sac at 4 weeks, which transforms into a polypoid mass between 5 and 7 weeks of gestation. The hydropic changes of the villous tissue is progressive and rarely visible in utero on ultrasound before 8 weeks of gestation. These findings should allow an earlier diagnosis and assist in the management counselling of women with CHM. [ABSTRACT FROM AUTHOR]

The most common site of metastasis in gestational trophoblastic disease (GTD) is the lung. To the best of our knowledge, arteriovenous malformations (AVMs) associated with pulmonary metastatic lesions are extremely rare in patients with GTD. Here, we report a case of a nineteen-year-old woman who presented with pulmonary AVMs which developed in the areas of pulmonary metastases, complicated by recent hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop a serum human chorionic gonadotropin (hCG) normogram for both uneventful complete and partial hydatidiform moles in the firsttrimester ultrasound era. Methods: An hCG normogram for both complete and partial hydatidiform moles was constructed, based on 639 patients with uneventful serum hCG regression after evacuation between 1990 and 2014. Serum hCG was measured by an in-houseYdeveloped radioimmunoassay, detecting both intact hCG and free β-subunit. It has been in use for all serum measurements sent to the Dutch Central Registry for Hydatidiform Moles since 1977. Results: Since introduction of routine first-trimester ultrasonography, lower preevacuation and follow-up serum hCG concentrations were observed. When compared with complete hydatidiform moles, patients with a partial hydatidiform mole had significantly lower pre-evacuation serum hCG concentration (median, 4400 and 875 ng/mL, respectively; P G 0.001) and earlier hCG normalization (median, 7 and 6 weeks, respectively; P G 0.001) but higher gestational age (mean, 11.5 and 13.0 weeks, respectively; P G 0.001). For both complete and partial hydatidiform moles, 95% of patients reached normal serum hCG concentrations within 14 weeks after evacuation. Conclusions: A normogram for the detection of gestational trophoblastic neoplasia was developed for complete and partial hydatidiform moles. Although interesting from a scientific perspective, the small divergence in hCG regression between complete and partial hydatidiform moles will be of little importance in clinical practice, as actual differences in regression will encompass only days. To promote clarity and unity in daily practice, we therefore propose a combined normogram to be used as a reference guideline for follow-up after evacuation of a hydatidiform mole. This normogram will be compliant with patients in today's clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes. Methods: We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylineosin-safran-stained slides. Results: PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles,ATS scores were maximal at 8 in 100%, 100%, and 75%of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity. Conclusions: We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti-PD-L1 drug in GTD patients has been activated. [ABSTRACT FROM AUTHOR]

Objective: Women older than 40 years develop gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) more often than do younger women. Therefore, in elderly women, primary hysterectomy has been advocated as first-line treatment. The aim of the present study was to evaluate whether hysterectomy could reduce the incidence of GTN after a diagnosis of HM. Methods: Seventy-six of 442 patients referred to our unit for an HM between 1994 and 2015 were older than 40 years old. Among these, 12 patients were treated by primary hysterectomy. We compared clinical features, serum human chorionic gonadotrophin (hCG), incidence of GTN, and further treatments in these patients and in those who underwent evacuation and serum hCG monitoring, using univariate and multivariate analyses. Results: Patients treated by primary hysterectomy all had a diagnosis of a complete or invasive HM, had more hyperemesis than did control subjects (82% vs 37%, P = 0.008), and had an increased uterine volume (100% vs 41%, P = 0.001). Seven of them developed a subsequent GTN, whereas 5 patients achieved complete remission of disease after surgery (58% vs 30%, P = 0.094). All the patients who developed a GTN after surgery showed lower hCG levels than did control subjects (mean, 671.4 [SD, 1178.4] IU/L vs 23,919.4 [SD, 34,284.9] IU/L; P = 0.005), but there were no significant differences in the amount and type of chemotherapy needed to achieve remission. Conclusions: Primary hysterectomy after 40 years old in women affected by HM does not reduce the incidence of GTN and amount of chemotherapy. Although further studies are needed to confirm these results, a careful hCG monitoring should be recommended in these high-risk patients. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to make clear whether miR-21 was dysregulated in hydatidiform mole (HM) tissues and choriocarcinoma (CCA) cells, to elucidate whether aberrant miR-21 expression would affect the function of CCA cells, and to find out whether there was a relationship between miR-21 and AKT , PDCD4 , and PTEN in CCA cells. Methods: Fresh and formalin-fixed, paraffin-embedded trophoblastic tissues (normal first trimester placentas and HMs) were retrieved from the biobank in the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University. Choriocarcinoma JAR and JEG-3 cells were cultured. Expression of miR-21 in trophoblast cells and tissues was examined by quantitative real-time polymerase chain reaction. Location and distribution of miR-21 in trophoblast tissues were determinated by in situ hybridization and fluorescent in situ hybridization. The effect of miR-21 on JAR and JEG-3 cells was tested by miR-21 mimics and inhibitor transfection, followed by cell viability assay, flow cytometric analysis, and Transwell analysis. Interaction between miR-21 and its target genes in CCA cells was verified by quantitative real-time polymerase chain reaction, Western blot, and luciferase report system. Results: We originally found miR-21 was markedly upregulated in HM tissues compared with normal first trimester placentas. The expression of miR-21 was exclusively confined in trophoblastic layers. Furthermore, we discovered miR-21 was significantly increased in JAR and JEG-3 cells compared with normal primary human trophoblastic cells. Moreover, we demonstrated miR-21 could promote proliferation, migration, and invasion of CCA cells. We furthermore proved miR-21 negatively regulated PDCD4 and PTEN in CCA cells and targeted to PDCD4 3′UTR directly. In addition, we confirmed that miR-21 could activate Akt pathway by phosphorylating Akt at Ser 473. Conclusions: Our results suggested miR-21 was responsible for aggressive phenotype of gestational trophoblastic disease and had the potential diagnostic and therapeutic values for gestational trophoblastic neoplasm. [ABSTRACT FROM AUTHOR]

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Introduction: Preeclampsia is currently thought to be induced by a placental factor that triggers maternal endothelial activation. It is now well known that trophoblastic debris shed from the placenta into the maternal blood is associated with this disease. Hydatidiform mole is a pathological pregnancy characterised by hyperplastic trophoblast with little or no fetal development. Women with molar pregnancies may exhibit symptoms resembling preeclampsia. Deportation of trophoblastic debris occurs in molar pregnancies but, whether trophoblastic debris from molar pregnancies expresses pathogenic signals or activates endothelial cells is unknown.Methods: Trophoblastic debris were collected from either hydatidiform molar or normal first trimester placental explants and then exposed to monolayers of endothelial cell for 24 h. Endothelial cell activation was measured by quantifying cell-surface ICAM-1using ELISA. In addition, the expressions of High mobility group box 1(HMGB1) and heat shock protein 70 (HSP70) on molar placenta were examined by immunohistochemistry and western blotting. Circulating levels of sEndoglin in molar pregnancy was also measured.Results: Exposing trophoblastic debris from molar placentae increased endothelial cell surface ICAM-1 expression compared to endothelial cells exposed to trophoblastic debris from controls. Expression of HSP70 but not HMGB1 was significantly increased in hydatidiform molar placentae. The circulating levels of sEndoglin in hydatidiform molar pregnancy were not increased compared to controls.Discussion: Our results suggest that trophoblastic debris from molar pregnancies induces endothelial cell activation. HSP70 but not HMGB1 expressed on hydatidiform molar placenta may be a pathogenic signal to endothelial cells. [ABSTRACT FROM AUTHOR]

Objective: Reports on the incidence of hydatidiform mole (HM) have varied depending on study population and methodology. This institutional-based study was undertaken to identify the incidence of HM in a modern obstetric practice using advanced laboratory diagnostic techniques. Methods: A retrospective review of consecutive hospital cases of HM was conducted for a 27-month period. Pathologic diagnoses of partial mole (PM) and complete mole (CM) were based on histopathologic assessment and selective use of p57 immunohistochemistry and molecular genotyping (MG) using formalin-fixed paraffin-embedded tissues. Results: During the study period, 14,944 obstetric deliveries took place at our institution. Forty-nine cases of HM (18 CMs, 31 PMs) were identified. Histopathology with the selective use of p57 immunohistochemistry was used in 25 of 49 HMs (18 CMs, 7 PMs). Histopathologic features were equivocal in the remaining cases (24/49 cases), and adjunctive MG was performed; all were PMs. The incidence of HM was 3.3/1000 deliveries. Partial mole was more prevalent with a CM (PM ratio, 1:1.72). Conclusions: Our observed incidence of HM is greater than previous studies and is attributable to improved detection of PM cases. Molecular genotyping and cytogenetic evidence indicate that CM is almost half as common as PM. This ratio may be useful in benchmarking laboratory diagnosis and HM registries. [ABSTRACT FROM AUTHOR]

Introduction: Development of normal placenta requires regulated apoptosis of trophoblasts. However, uncontrolled apoptosis has been seen in the pregnancy related complications like hydatidiform mole and pre-eclampsia. STAT5A is a transcription factor with well-known anti-apoptotic role. Thus, we sought to study the role of STAT5A and its epigenetic regulation in placental development and pathologies and its use as fetal DNA epigenetic marker.Methods: The present study was conducted on pregnant women who were enrolled in five groups, based on the three trimesters in normal pregnancy and two pregnancy related disorder groups: pre-eclampsia and hydatidiform mole. Placental villi samples and maternal blood were obtained from each pregnant woman and were analyzed for promoter region methylation (via methylation sensitive high resolution melting) and histone trimethylations (via chromatin immunoprecipitation) of STAT5A.Results: Our data revealed higher expression of STAT5A in first trimester villi, which decreased with advancing gestation with corresponding increased DNA methylation and H3 trimethylations. Development of choriocarcinoma was associated with DNA methylation associated lower expression of STAT5A. The pattern of promoter methylation of STAT5A in cell free DNA within maternal plasma was observed to be similar to its promoter methylation in placental villi during normal pregnancy, pre-eclampsia and molar complications, which suggested its use as a novel fetal DNA epigenetic marker.Discussion: Our results suggest the regulation of STAT5A via epigenetic mechanisms during normal pregnancy and the association of STAT5A epigenetic dysregulation in pregnancy related complications. Further, hypermethylated STAT5A can be utilized as novel fetal DNA epigenetic marker. [ABSTRACT FROM AUTHOR]

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Objective: The aim of the study was to evaluate potential changes in the clinical, diagnostic, and therapeutic parameters of complete hydatidiform mole in the last 25 years in Brazil. Methods: A retrospective cohort study was conducted involving the analysis of 2163 medical records of patients diagnosed with complete hydatidiform mole who received treatment at the Rio de Janeiro Reference Center for Gestational Trophoblastic Disease between January 1988 and December 2012. For the statistical analysis of the natural history of the patients with complete molar pregnancies, time series were evaluated using the Cox- Stuart test and adjusted by linear regression models. Results: A downward linear temporal trend was observed for gestational age of complete hydatidiform mole at diagnosis, which is also reflected in the reduced occurrence of vaginal bleeding, hyperemesis and pre-eclampsia. We also observed an increase in the use of uterine vacuum aspiration to treat molar pregnancy. Although the duration of postmolar follow-up was found to decline, this was not accompanied by any alteration in the time to remission of the disease or its progression to gestational trophoblastic neoplasia. Conclusions: Early diagnosis of complete hydatidiform mole has altered the natural history of molar pregnancy, especially with a reduction in classical clinical symptoms. However, early diagnosis has not resulted in a reduction in the development of gestational trophoblastic neoplasia, a dilemma that still challenges professionals working with gestational trophoblastic disease. [ABSTRACT FROM AUTHOR]