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Abstract

Gestational trophoblastic disease (GTD) includes a wide variety of clinical and histopathologic entities that require prompt identification and definition by the integration of clinical, laboratory, and imaging data. Recently, the role of grayscale ultrasound and spectral and power/color Doppler techniques has become pivotal in the diagnosis, staging, and management of GTD, thanks to both technical improvements and the growing expertise of dedicated operators. The aim of this essay is to summarize the most recent data on the ultrasound and Doppler findings of GTD and to provide a pictorial overview, including useful prognostic and therapeutic implications for clinical practice.

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... For instance, gestational trophoblastic neoplasia (GTN) tumor is another cause of vascular malformation due to arterio-venous shunts deriving from neoangiogenesis phenomena within the tumor mass. Differential diagnosis of myometrial nodules is represented by benign masses such as uterine fibroids, which usually appear as solid or partially colliquated masses, or focal adenomyosis, which can be ruled out by the lack of exaggerated vascularity in color Doppler flow imaging [38]. This is particularly important Detection of vascular malformation within the uterus is not straightforward and differential diagnosis must be carried out to consider the full range of possibilities. ...
... For instance, gestational trophoblastic neoplasia (GTN) tumor is another cause of vascular malformation due to arterio-venous shunts deriving from neoangiogenesis phenomena within the tumor mass. Differential diagnosis of myometrial nodules is represented by benign masses such as uterine fibroids, which usually appear as solid or partially colliquated masses, or focal adenomyosis, which can be ruled out by the lack of exaggerated vascularity in color Doppler flow imaging [38]. This is particularly important when assessing the patient without knowledge of BhCG testing to indicate requirement for the test. ...
... This is particularly important when assessing the patient without knowledge of BhCG testing to indicate requirement for the test. This is particularly as the US picture of vascular abnormality can persist after negativization of BHCG [38]. ...
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An acquired uterine artery myometrial pseudoaneurysm can occur due to inflammation, trauma, or iatrogenic causes, such as surgical procedures, and can lead to profuse bleeding. The efficacy of uterine manipulators in gynecological surgery, particularly as a cause of a pseudoaneurysm, has been poorly discussed in the literature. In this paper, we discuss a case of a 39-year-old woman with profuse uterine bleeding that occurred seven days after operative laparoscopic surgery for endometriosis. The color Doppler ultrasound better evoked the arterial-like turbulent blood flow inside this cavity. These sonographic features were highly suggestive of uterine artery pseudoaneurysm, presumably related to a secondary trauma caused by the manipulator. The diagnosis was subsequently re-confirmed by angiography, and the patient was treated conservatively with uterine artery embolization. Ultrasound has been shown to be a valuable and safe tool for imaging pseudoaneurysm and guiding subsequent interventional procedures. Accordingly, we briefly review the most suitable manipulators used in benign gynecological surgeries to verify if the different types in use can guide the surgeon towards the correct choice according to surgical needs and thus prevent potentially dangerous trauma.
... However, PHM presents subtler US features so that its diagnosis is less common than CHM during first trimester. Early PHMs are characterized by cystic changes and increased echogenicity of the decidua and placenta in presence of embryonic tissue that can be identified as amorphous echoes (42,43). In those few cases that proceed above 11 weeks (late PHMs), US features are characterized by enlarged and irregular molar placenta with focal villous edema and an abnormal triploid fetus carrying severe abnormalities (ventriculomegaly, hydrocephalus, holoprosencephaly, increased nuchal translucency, renal defects). ...
... US findings of vascularized myometrial nodules after uterine evacuation can correlate with a high risk of malignant evolution (46). Arteriovenous shunts are also common due to neoangiogenesis phenomena occurring within the tumor (43). ...
... Their rarity makes diagnosis particularly challenging. US features are similar to other forms of GTN, i.e., the presence of myometrial nodules with a heterogeneous structure consisting of cystic cavities and solid masses (43). At US, they show different patterns of myometrial invasion: while ETT expands with sharp borders, PSTT penetrates between myometrium muscle fibers (47). ...
... Microscopic examination demonstrated a circumferential proliferation of abnormal hyperchromatic trophoblastic cells surrounding edematous hydropic villi invading the myometrium, with a few scattered trophoblastic cells within blood vessels (Figs. 4,5,6,7,8,9,10,11,12,13). ...
... Transabdominal ultrasonography (USG) is considered the first-line imaging method for the initial diagnosis of GTNs and for demonstrating the characteristic vesicular appearance. It is also reliable for monitoring processes in patients with elevated serum b-HCG [12]. However, transvaginal USG is considered to have higher specificity in differentiating pelvic masses, while computed tomography (CT) and magnetic resonance imaging (MRI) are recommended for the staging process and detecting metastatic lesions, as in our case [13]. ...
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Background Invasive mole is a subtype of gestational trophoblastic neoplasms (GTNs) that usually develops from the malignant transformation of trophoblastic tissue after molar evacuation. Invasive moles mostly occur in women of reproductive age, while they are extremely rare in postmenopausal women. Case presentation We present the case of a 55-year-old postmenopausal Syrian woman who was admitted to the emergency department at our hospital due to massive vaginal bleeding for 10 days accompanied by constant abdominal pain with diarrhea and vomiting. Following clinical, laboratory and radiological examination, total hysterectomy with bilateral salpingo-oophorectomy was performed. Histologic examination of the resected specimens revealed the diagnosis of an invasive mole with pulmonary metastases that were diagnosed by chest computed tomography (CT). Following surgical resection, the patient was scheduled for combination chemotherapy. However, 2 weeks later the patient was readmitted to the emergency department due to severe hemoptysis and dyspnea, and later that day the patient died in spite of resuscitation efforts. Conclusion Although invasive moles in postmenopausal women have been reported previously, we believe our case is the first reported from Syria. Our case highlights the difficulties in diagnosing invasive moles in the absence of significant history of gestational trophoblastic diseases. The present study further reviews the diagnostic methods, histological characteristics and treatment recommendations.
... The neoplasm is highly vascular and is associated with massive hemorrhage. Selective arterial embolization can effectively control the bleeding, and 3D PD using glass body surface rendering may aid in the POC color flow mapping of a uterine arteriovenous malformation with high vascularity associated with a gestational trophoblastic neoplasia [74]. ...
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Realistic reconstruction of angioarchitecture within the morphological landmark with three-dimensional sonoangiography (three-dimensional power Doppler; 3D PD) may augment standard prenatal ultrasound and Doppler assessments. This study aimed to (a) present a technical overview, (b) determine additional advantages, (c) identify current challenges, and (d) predict trajectories of 3D PD for prenatal assessments. PubMed and Scopus databases for the last decade were searched. Although 307 publications addressed our objectives, their heterogeneity was too broad for statistical analyses. Important findings are therefore presented in descriptive format and supplemented with the authors’ 3D PD images. Acquisition, analysis, and display techniques need to be personalized to improve the quality of flow-volume data. While 3D PD indices of the first-trimester placenta may improve the prediction of preeclampsia, research is needed to standardize the measurement protocol. In highly experienced hands, the unique 3D PD findings improve the diagnostic accuracy of placenta accreta spectrum. A lack of quality assurance is the central challenge to incorporating 3D PD in prenatal care. Machine learning may broaden clinical translations of prenatal 3D PD. Due to its operator dependency, 3D PD has low reproducibility. Until standardization and quality assurance protocols are established, its use as a stand-alone clinical or research tool cannot be recommended.
... Transvaginal ultrasound (US) has acquired a substantial role in diagnosing and managing GTNs with the development of Doppler techniques. [7][8][9] GTNs and other benign pregnancy-related uterine diseases can sometimes appear similar on greyscale and colour Doppler US, manifesting as focal lesions with rich blood flow signals. 10 Hence, it is crucial to develop new imaging methods as a complement to conventional US for diagnosing GTNs. ...
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Objective: We aimed to compare the imaging features of gestational trophoblastic neoplasias (GTNs) and benign pregnancy-related uterine diseases on contrast-enhanced ultrasound (CEUS) to explore the clinical value of CEUS in differentiating these two types of uterine lesions. Materials and methods: In this prospective study, patients with GTNs before and after chemotherapy and benign pregnancy-related uterine lesions received conventional US and CEUS. The imaging features and parameters of CEUS of the lesions were assessed. Results: A total of 73 patients were enrolled in this study, including 48 with GTNs and 25 with benign lesions. The enhancement pattern of newly diagnosed GTNs was mainly diffuse enhancement (70.8%), with a non-enhanced area of less than 1/3 of the entire lesion. For the benign group, the enhancement pattern was mainly ring-shaped enhancement (72.0%), and the non-enhanced area was more than 1/2 (68.0%), significantly different from that of GTNs (P = 0.000 and 0.002, respectively). Forty-one lesions demonstrated unclear boundaries on greyscale US but clearly displayed on CEUS. In both the benign and malignant groups, the measurements of lesion size on CEUS were larger than those on greyscale US (P = 0.000). The measurement differences (ΔD: D2-D1) of the malignant cases were higher than those of the benign cases (P = 0.001). Conclusion: GTNs and benign pregnancy-related uterine diseases have different imaging characteristics on CEUS. The boundary and involved range of the lesion can be clearly demonstrated on CEUS. CEUS possesses clinical value in diagnosing and evaluating GTNs and benign pregnancy-related diseases.
Article
Purpose: The aim of this study was to investigate the role of 18F-FDG PET/CT in predicting pathological prognostic factors, including tumor type and International Federation of Gynecology and Obstetrics (FIGO) score, in gestational trophoblastic disease (GTD). Methods: Retrospective monocentric study including 24 consecutive patients who underwent to 18F-FDG PET/CT from May 2005 to March 2021 for GTD staging purpose. The following semiquantitative PET parameters were measured from the primary tumor and used for the analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolisis (TLG). Statistical analysis included Spearman correlation coefficient to evaluate the correlations between imaging parameters and tumor type (nonmolar trophoblastic vs postmolar trophoblastic tumors) and risk groups (high vs low, defined according to the FIGO score), whereas area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive value of the PET parameters. Mann-Whitney U test was used to further describe the parameter's potential in differentiating the populations. Results: SUVmax and SUVmean resulted fair (AUC, 0.783; 95% confidence interval [CI], 0.56-0.95) and good (AUC, 0.811; 95% CI, 0.59-0.97) predictors of tumor type, respectively, showing a low (ρ = 0.489, adjusted P = 0.030) and moderate (ρ = 0.538, adjusted P = 0.027) correlation. According to FIGO score, TLG was instead a fair predictor (AUC, 0.770; 95% CI, 0.50-0.99) for patient risk stratification. Conclusions: 18F-FDG PET parameters have a role in predicting GTD pathological prognostic factors, with SUVmax and SUVmean being predictive for tumor type and TLG for risk stratification.
Chapter
In this chapter we describe on overview of placental development, and its physiologic and pathologic appearance on ultrasound examination, and for some features additional modalities such as magnetic resonance imaging (MRI). We explain the mechanisms of ultrasound and MRI, and the development of these techniques within the last decades. The main focus of this chapter will be on antenatal ultrasound imaging since other modalities are not readily available and are therefore less commonly applied in daily obstetric practice.
Article
High myopia continues to progress and the eye axis continues to grow, resulting in mechanical dilatation of the eyeball wall, and with the increase of age, resulting in a variety of myopic fundus pathological changes. Considering that in the late stage of fundus disease, patients can obviously feel the impact of the disease on vision, and ophthalmologists are needed for direct diagnosis, intervention and treatment. The impact of early lesions on vision is relatively weak, and patients can not detect the emergence of these lesions in time, which can only be found by fundus survey. Therefore, the automatic detection of early lesions of fundus disease (especially microaneurysms) is not only of great significance for early diagnosis and early treatment of fundus disease, but also a good reference for the detection of other fundus diseases. In this paper, color ultrasound can effectively analyze the origin of fundus diseases. The results showed that with the changes of age, eye axis and posterior sclera shape in high myopia, the area and range of myopic arc and choroidal atrophy arc expanded, the thickness of nerve fiber and choroid became thinner, and the fovea of macula mainly shifted vertically. In addition, it was also found that myopic arc, choroidal atrophic arc area, retinal thickness, nerve fiber thickness, choroidal thickness, vertical distance from macular fovea to optic disc center were correlated with age and eye axis.
Article
Objective To evaluate the role of hysteroscopy and ultrasound in early identification of gestational trophoblastic neoplasia (GTN) after molar evacuation. Methods This was a prospective study involving 52 women with an ultrasound diagnosis of complete hydatidiform mole, attending a tertiary centre in south India between August 2016 and August 2019. Baseline characteristics such as age, serum beta-human chorionic gonadotropin(β-hCG) level, gestational age, and uterine size were noted. After the evacuation of molar pregnancy, weekly follow-up with β-hCG was performed, until three consecutive values were normal and then monthly for six months. Findings of transvaginal ultrasound and diagnostic hysteroscopy, performed on follow up at three weeks, were noted. Primary outcome was the development of GTN. Area under the curve(AUC) was calculated to assess the usefulness of these methods in early identification of GTN. Results Thirteen women (25 %) developed GTN during follow up, within 6 months. Twenty six(50 %) cases had high-risk molar pregnancy. Positive findings on hysteroscopy and ultrasonography were noted in 44.2 % and 19.2 % respectively. AUC was 0.83(95 % CI, 0.70−0.97) for ultrasound and 0.82(95 % CI, 0.72–.92) for hysteroscopy. Sensitivity and specificity were 69.2 % and 97.4 % for ultrasound and it was 92.3 % and 71.8 % respectively for hysteroscopy in identifying those who developed GTN on follow-up. Conclusions Transvaginal ultrasound as well as hysteroscopy may help in early identification of women at risk of developing GTN following a molar evacuation. Being a non-invasive method with similar discriminative value, ultrasonographic evaluation may be used for early identification of women with GTN after validation in future studies.
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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.
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OBJECTIVES Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon’s test, logistic regression, and ROC analysis. RESULTS No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS Uterine Doppler flow velocimetry measurements, particularly pre- and post-molar evacuation pulsatility indices, can be useful for predicting postmolar gestational trophoblastic neoplasia.
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Gestational trophoblastic neoplasia (GTN) represents a group of diseases characterized by production of human chorionic gonadotropin (hCG). Since non-gestational tumors may occasionally secrete hCG, histopathological diagnosis is important for appropriate clinical management. However, a histopathological diagnosis is not always available. We therefore investigated the feasibility of extracting cell free DNA (cfDNA) from the plasma of women with GTN for use as a “liquid biopsy” in patients without histopathological diagnosis. cfDNA was prepared from the plasma of 20 women with a diagnosis of GTN and five with hCG-secreting tumors of unknown origin. Genotyping of cfDNA from the patient, genomic DNA from her and her partner and DNA from the tumor tissue identified circulating tumor DNA (ctDNA) (from 9% to 53% of total cfDNA) in 12 of 20 patients with GTN. In one case without a tissue diagnosis, ctDNA enabled a diagnosis of GTN originating in a non-molar conception and in another a diagnosis of non-gestational tumor, based on the high degree of allelic instability and loss of heterozygosity in the ctDNA. In summary ctDNA can be detected in the plasma of women with GTN and can facilitate the diagnosis of both gestational and non-gestational trophoblastic tumors in cases without histopathological diagnosis.
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As epithelioid trophoblastic tumor (ETT) shares similar clinical features with other gestational trophoblastic neoplasms (GTNs), it is likely to be clinically misdiagnosed and subsequently treated in an improper way. This study aimed to identify the sonographic features of ETT that are distinct from other GTNs, including placental site trophoblastic tumor (PSTT) and invasive mole/choriocarcinoma (IM/CC). Here, we retrospectively analyzed ultrasound images of 12 patients with ETT in comparison with those of 21 patients with PSTT and 24 patients with IM/CC. The results showed that maximal diameter and hemodynamic parameters were not significantly different among ETT, PSTT and IM/CC (P>0.05). However, a well-circumscribed border with hypoechogenic halo was identified in the gray-scale sonogram in all 12 cases of ETT, while only in 1 out of 21 cases of PSTT and 1 out of 16 cases of IM/CC (P<0.001 for ETT vs. PSTT or IM/CC). Moreover, a peripheral pattern of Doppler signals was observed in 11 out of 12 ETT lesions, showing relatively more Doppler signal spots around the tumor border than within the boundary, while a non-peripheral pattern of Doppler signals in all 21 PSTT cases and 14 out of 16 IM/CC cases: with minimal, moderate or remarkable signal spots within the tumor, but not along the tumor (P<0.001 for ETT vs. PSTT or IM/CC). These distinct sonographic features of ETT correlated with histopathologic observations, such as expansive growth pattern and vascular morphology. Thus, we draw the conclusions that the well-circumscribed border with peripheral Doppler signal may serve as a reliable sonographic feature to discriminate ETT from other types of GTNs. With further validation in a larger patient set in our ongoing multi-center study, this finding will be potentially developed into a non-invasive pre-operative GTN subtyping method for ETT.
Article
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Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β -hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity.
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Objective: To investigate potential performance of cell-free DNA (cfDNA) testing in maternal blood in detecting fetal triploidy. Methods: Plasma and buffy coat samples obtained at 11-13 weeks' gestation from singleton pregnancies with diandric triploidy (n=4), digynic triploidy (n=4), euploid fetuses (n=48) were sent to Natera, Inc. (San Carlos, Calif., USA) for cfDNA testing. Multiplex polymerase chain reaction amplification of cfDNA followed by sequencing of single nucleotide polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm which identifies copy number for each of the five chromosomes. Results: cfDNA testing provided a result in 44 (91.7%) of the 48 euploid cases and correctly predicted the fetal sex and the presence of two copies each of chromosome 21, 18 and 13. In diandric triploidy, cfDNA testing identified multiple paternal haplotypes (indicating fetal trisomy 21, trisomy 18 and trisomy 13) suggesting the presence of either triploidy or dizygotic twins. In digynic triploidy the fetal fraction corrected for maternal weight and gestational age was below the 0.5th percentile. Conclusions: cfDNA testing by targeted sequencing and allelic ratio analysis of single nucleotide polymorphisms covering chromosomes 21, 18, 13, X, and Y can detect diandric triploidy and raise the suspicion of digynic triploidy.
Article
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The Uterine Artery Pulsatility Index (UAPI) is an ultrasound measure of tumour vascularity. In this study, we hypothesised that a UAPI ≤1 (high vascularity) would identify women with gestational trophoblastic neoplasia (GTN) at increased risk of resistance to first-line single-agent methotrexate (MTX-R). Single-centre cohort study. Charing Cross Hospital, a UK national centre for the treatment of trophoblastic disease. All women with a GTN FIGO score 5-6 treated with methotrexate (n = 92), between 1999 and 2011, at Charing Cross Hospital. UAPI was measured before the start of chemotherapy, and women were monitored for the development of MTX-R. Frequency of MTX-R in women with UAPI ≤1 compared with UAPI >1. UAPI was measured before chemotherapy in 73 of 92 women with GTN FIGO score 5-6. UAPI ≤1 predicted MTX-R independent of the FIGO score (hazard ratio 2.9, P = 0.04), with an absolute risk of MTX-R in women with a UAPI ≤1 of 67% (95% CI 53-79%) compared with 42% (95% CI 24-61%) with a UAPI >1 (P = 0.036). Our results suggest UAPI is an independent predictor of MTX-R in women with FIGO 5-6 GTN.
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The aim of this study was to evaluate the usefulness of maternal serum markers in the early prenatal diagnosis of molar pregnancies. The ultrasound features, cytogenetic and histopathological findings of 10 cases of molar pregnancy diagnosed at 11-13 weeks of gestation were compared retrospectively with the maternal serum concentrations of human chorionic gonadotrophin (HCG), alpha fetoprotein (AFP), pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1). Free beta-HCG and intact HCG concentrations were very high [> or = 2.5 multiples of the median (MoM)] in all cases. AFP concentrations were extremely low in all cases of singleton complete moles (< or = 0.5 MoM) and were high in one case of twin complete mole, in one case of triploid partial mole and two cases of euploid partial mole (> or = 2.5 MoM). Serum PAPP-A and SP1 were high in complete moles. The combined use of ultrasound features, maternal serum proteins and fetal cytogenetic findings should enable the early differential diagnosis in utero and perinatal management of those molar pregnancies presenting with an anatomically normal fetus.
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To relate uterine artery blood flow characteristics to serum human chorionic gonadotropin (hCG) levels in patients with gestational trophoblastic disease (GTD). Twenty-one patients with GTD were investigated by serum hCG titers and Doppler ultrasonography of uterine arteries. The relations between the Doppler indices and the serum hCG titers were evaluated by paired-t, Mann-Whitney U tests, and Pearson's correlation analysis. Significant but weak negative correlations were observed between systole/diastole (S/D) ratios, resistance indices (RIs) and pulsatility indices (PIs) and the absolute values of serum hCG levels with correlation coefficients of -0.31, -0.37, and -0.33 (P < 0.05). However, the same Doppler indices had more significant and strong negative correlations with the logarithmic values of the serum hCG levels with correlation coefficients of -0.65, -0.58, and -0.63, respectively (P < 0.01). Five patients who received chemotherapy had significantly lower Doppler indices than those 16 patients with spontaneous regression (P < 0.001). Uterine artery Doppler indices might be used for the surveillance of the patients with GTD.
Article
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).
Article
Objective: To examine factors affecting the rate of failure to obtain a result from cell-free DNA (cfDNA) testing of maternal blood for fetal trisomies 21, 18 and 13 in singleton and twin pregnancies in the first trimester. Methods: This was a prospective study of 23 495 singleton and 928 twin pregnancies undergoing screening for fetal trisomy by targeted cfDNA testing at 10 + 0 to 14 + 1 weeks' gestation. Multivariate logistic regression analysis was used to determine significant predictors of failure to obtain a result after first sampling. Results: There was no result from cfDNA testing after first sampling in 3.4% (798/23 495) of singletons, 11.3% (91/806) of dichorionic twins and 4.9% (6/122) of monochorionic twins. Multivariate logistic regression analysis demonstrated that the risk of test failure, first, increased with increasing maternal age (odds ratio (OR), 1.02; 95% CI, 1.01-1.04) and weight (OR, 1.05; 95% CI, 1.04-1.05), decreasing gestational age (OR, 0.85; 95% CI, 0.79-0.91), serum pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) (OR, 0.56; 95% CI, 0.49-0.65) and free β-human chorionic gonadotropin (β-hCG) MoM (OR, 0.67; 95% CI, 0.60-0.74), second, was higher in women of black (OR, 1.72; 95% CI, 1.33-2.20) and South Asian (OR, 1.99; 95% CI, 1.56-2.52) than those of white racial origin, in dichorionic twin than in singleton pregnancy (OR, 1.75; 95% CI, 1.34-2.26) and in pregnancies conceived by in-vitro fertilization than in those conceived naturally (OR, 3.82; 95% CI, 3.19-4.55) and, third, was lower in parous than in nulliparous women (OR, 0.63; 95% CI, 0.55-0.74). Conclusions: Maternal age, weight, racial origin and parity, gestational age, dichorionicity, method of conception and serum levels of free β-hCG and PAPP-A are independent predictors of cfDNA test failure. The risk of test failure is higher in dichorionic twin than in singleton pregnancies, mainly because a higher proportion of twins are conceived by in-vitro fertilization and more of the women are nulliparous. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Article
One partial and three complete moles were studied using the HDliveFlow silhouette mode with HDlive silhouette mode (Voluson E10, GE Healthcare Japan, Tokyo, Japan). The case of typical complete mole was reported previously by our group, using different rendering techniques for 3D examinations of the molar pregnancy [1]. This article is protected by copyright. All rights reserved.
Article
Purpose Cell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). Methods A prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). Results Overall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. Conclusion cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.
Article
Purpose To assess the prospective sonographic diagnosis of molar pregnancy and compare sonographic features of complete versus partial molar pregnancy. Methods This institutional review board‐‐approved retrospective chart review conducted between 2001 and 2011 identified 70 women with a histopathologic diagnosis of molar pregnancy and with available sonograms. Clinical data, images, and reports were reviewed, and features enumerated by radiologists blinded to the final diagnosis. Results Mean age of patients was 30.5 ± 7.0 (SD) years (range, 16–49 years) with a mean gravidity of 3.2 ± 2.3 (SD) (range 1–11). Mean gestational age was 74.0 ± 19.1 day (range 39–138) and serum β‐human chorionic gonadotropin was 131 ± 156 mIU/ml (range 447–662,000). Pathologic results showed 48 partial and 22 complete molar pregnancies. Sonographically, partial moles more commonly showed a yolk sac (56.3% versus 0%, p < 0.0001), fetal pole (62.5% versus 4.6%, p < 0.0001), fine septa within the sac (25.0% versus 4.6%, p = 0.05), and normal (31.3% versus 0%, p = 0.002) or minimally cystic placenta (27.1% versus 4.6%, p = 0.49), while complete moles had larger gestational sacs (612 versus 44 mm, p = 0.005), were more often avascular on color Doppler imaging (45.5% versus 18.8%, p = 0.02), had more often abnormal tissue in the uterus (82.6% versus 20.8%, p < 0.0001) and placental masses (86.9% versus 16.7%, p < 0.0001), and were more often diagnosed prospectively (86.4% versus 41.7%, p = 0.0005). Conclusions Complete molar pregnancy is associated with marked cystic changes and mass formation and is often diagnosed sonographically. Partial molar pregnancy often presents with minor cystic changes of the placenta and remains underdiagnosed sonographically. However, correct prospective diagnosis was made more frequently in this study than in older reports, perhaps due to improved spatial resolution of sonographic equipment. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:72–78, 2017;
Article
Aim: The study aimed to describe prenatal diagnosis and the outcome of complete hydatidiform mole and coexistent normal fetus (CHMCF). Methods: This was a retrospective case series of 13 patients with CHMCF. Prenatal diagnosis, outcome and development of gestational trophoblastic neoplasia (GTN) were reviewed. Results: Ultrasound diagnosis was carried out in 12 of 13 cases at 17 ± 2.7 weeks of gestation (mean ± SD). Six patients showed abnormalities suggestive of subchorionic hematoma on first trimester ultrasonography (US). Prenatal invasive procedures were performed in 8 of 13 cases (62%). Two women decided to terminate their pregnancies. Four ended in late miscarriages (36%, 4 of 11) between 13 and 21 weeks, and early neonatal death occurred in 1 case (9%, 1 of 11); 5 women delivered a live baby with a mean gestational age of 31 weeks (range 26-37 weeks) with an overall neonatal survival of 45% (5 of 11). GTN occurred in 31% of cases (4 of 13). Conclusions: The first trimester US features of CHMCF are not well-documented. Our series showed that abnormalities of CHMCF could be misdiagnosed as subchorionic hematoma in the early first trimester. When CHMCF is confirmed by expert US, prenatal invasive procedures should be carefully evaluated depending on the associated US findings and exhaustive counseling should be performed.
Article
Objective: To report the clinical features, management, and outcome of twin pregnancies consisting of a complete hydatidifom mole and a coexisting normal fetus. Methods: Between 1966 and 1997, seven women with complete hydatidiform mole and coexisting normal fetus were treated at the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School. Clinical features, including presenting symptoms, gestational dates, hCG levels, and complications, as well as route of delivery or evacuation, pregnancy outcome, genetic analysis, and need for chemotherapy were assessed. Results: Four women required uterine evacuation before 20 weeks' gestation because of vaginal bleeding or medical complications, one woman required an emergency hysterotomy because of hemorrhage at 24 weeks, and two women delivered normal, viable infants at 26 and 34 weeks. The pathologic diagnosis of complete hydatidiform mole was confirmed in each case and the chromosome complement was 46,XX in all molar gestations. Four of seven women required chemotherapy for treatment of nonmetastatic gestational trophoblastic tumors, including both women who delivered viable infants and two of the five women whose pregnancies were evacuated before 24 weeks' gestation. All four patients were treated with five to seven cycles of a 5-day methotrexate regimen and achieved complete remission. Conclusion: Patients with a twin pregnancy consisting of a complete mole and a normal fetus are at increased risk for hemorrhage and medical complications, as well as the development of persistent gestational trophoblastic tumor.
Article
The aim of this study was to evaluate the usefulness of maternal serum markers in the early prenatal diagnosis of molar pregnancies. The ultrasound features, cytogenetic and histopathological findings of 10 cases of molar pregnancy diagnosed at 11–13 weeks of gestation were compared retrospectively with the maternal serum concentrations of human chorionic gonadotrophin (HCG), alpha fetoprotein (AFP), pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific β1-glycoprotein (SP1). Free β-HCG and intact HCG concentrations were very high [≥ISOdia≥2.5 multiples of the median (MoM)] in all cases. AFP concentrations were extremely low in all cases of singleton complete moles (≤ISOdia≤0.5 MoM) and were high in one case of twin complete mole, in one case of triploid partial mole and two cases of euploid partial mole (≥ISOdia≥2.5 MoM). Serum PAPP-A and SP1 were high in complete moles. The combined use of ultrasound features, maternal serum proteins and fetal cytogenetic findings should enable the early differential diagnosis in utero and perinatal management of those molar pregnancies presenting with an anatomically normal fetus.
Article
Objective: The objective of this study was to provide a consensus review on gestational trophoblastic disease diagnosis and management from the combined International Society for the Study of Trophoblastic Disease, European Organisation for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup. Methods: A joint committee representing various groups reviewed the literature obtained from PubMed searches. Results and conclusions: Guidelines were constructed on the basis of literature review. After initial diagnosis in local centers, centralization of pathology review and ongoing care is recommended to achieve the best outcomes.
Article
Hyperreactio luteinalis (HL) is a rare benign condition complicating pregnancy with multicystic bilateral ovarian enlargement, increased serum βhCG levels and spontaneous regression after delivery. HL has been associated with complications of pregnancy and the aim of our research was to review the literature, and add a new unpublished case from our group. We searched the internet-based medical databases for case reports and case series of hyperreactio luteinalis and we evaluated diagnostic path, treatment and outcome of pregnancies. We found 96 cases of HL from 1955 to 2013. HL was asymptomatic in 28% of cases but in 72% of patients there were symptoms like lower abdominal pain, nausea and vomiting, ascites and signs of virilization. Suspicion of malignancy was raised in 38% of cases. Surgical treatment of various types was performed in 48% of cases, with oophorectomy in 40% of this group. Several complications were associated with HL, in particular preeclampsia (PE) occurred in 24% of cases and fetal growth restriction (FGR) in 12%. Mean gestation at delivery was 35 weeks (range 25-42). Although preoperative diagnosis occurred in most cases, suspicion of malignancy was extensive, as was oophorectomy, demonstrating suboptimal understanding of the underlying physiopathology. We propose a diagnostic algorithm for this condition. Training of obstetricians in making the correct diagnosis may prevent unnecessary oophorectomies and may lead to early diagnosis and correct management of associated complications.
Article
Weekly serum β-hCG measurements and transvaginal ultrasound scans coupled with color Doppler flow were performed on 8 patients with hydatidiform mole. Two patients later developed persistent trophoblastic disease, necessitating chemotherapy. The correlation coefficients between Doppler flow indices, systolic-diastolic (S/D) ratio and pulsatility index (PI) with log β-hCG were ––0.96 and ––0.97, respectively. The weekly S/D and PI indices were plotted on an individual curve. Only the 2 patients who developed persistent gestational trophoblastic disease had PI index levels of < 1.5 as early as 2 weeks after molar evacuation. At that stage their serum β-hCG levels were not different from some of the other patients. In this preliminary report, the regression of the disease could be reliably assessed by observing the changes in low resistance flow which paralleled the gradual decrements in serial β-hCG levels. Thus, the contribution of this noninvasive imaging technique encourages the authors to further investigate Doppler flow monitoring among a larger sample of patients suffering from various gestational trophoblastic diseases.Copyright © 1996 S. Karger AG, Basel
Article
Objective: To investigate clinical features and ultrasound findings in cases of placental site trophoblastic tumor (PSTT). Methods: Fourteen cases of PSTT treated at our institution between May 2004 and October 2010 were identified and the clinical features and findings on transvaginal sonography (TVS) were investigated. Pathological confirmation of PSTT was obtained in all cases. Results: The most frequent symptoms associated with PSTT were abnormal vaginal bleeding, which was present in 11 cases, and amenorrhea, which was present in five cases. The interval from antecedent pregnancy to diagnosis was 4-36 (median, 12.5) months. Blood serum was positive for beta-human chorionic gonadotropin (β-hCG) at the time of ultrasound examination, although the level was generally low, with a median of 166.2 IU/L (range, 4.5-3480.2). Sonographic presentation of PSTT was classified into one of three types according to the characteristics observed on TVS: Type I, heterogeneous solid mass in the uterine cavity (four cases), with minimal to a moderate degree of vascularization on color Doppler imaging; Type II, heterogeneous solid mass in the myometrium (six cases), with minimal to a high degree of vascularization (only one case was highly vascularized); and Type III, cystic lesions in the myometrium (four cases) with a high degree of vascularization (lacunar-type lesions). Conclusions: Combined with clinical features, characteristics demonstrated by TVS provide evidence for the suspicion of PSTT and could contribute to clinical decision making.
Article
Methotrexate (MTX) resistance is defined on the basis of the human chorionic gonadotropin (hCG) curve. The aim of this study was to identify low-risk non-metastatic patients with gestational trophoblastic neoplasia (GTN) who can achieve resolution by continuing MTX treatment despite a transient hCG plateau. Before starting chemotherapy, 24 patients with FIGO Stage I GTN underwent transvaginal ultrasonography with power Doppler in order to identify myometrial lesions (areas of increased echogenicity and increased power Doppler signal). Ultrasound response to chemotherapy was defined when myometrial lesions decreased in echogenicity, Doppler signal or size. When ultrasound response occurred, despite chemoresistance defined by hCG values, MTX treatment was continued. MTX was continued in three out of seven chemoresistant patients because ultrasound suggested response to MTX. All three of these patients achieved a complete response, thus nearly halving the MTX-resistance rate. Among patients who are candidates for second-line treatment on the basis of hCG, ultrasound may identify those in whom further MTX administration can induce a delayed complete response.
Article
Gestational trophoblastic disease is a spectrum of disorders of varying malignant potential arising from trophoblastic cells and encompassing hydatidiform moles and persistent trophoblastic neoplasia. Ultrasound is the initial imaging investigation of choice when gestational trophoblastic disease is suspected. Complete hydatiform mole, the most common form of molar pregnancy, usually has a characteristic "cluster of grapes" appearance, especially on second-trimester ultrasounds. Persistent trophobastic neoplasia usually appears as a focal, hypervascular myometrial mass on pelvic ultrasound. Pelvic magnetic resonance imaging is often used as a problem-solving tool in equivocal or complicated cases of gestational trophoblastic disease to assess the degree of invasion into the myometrium and surrounding tissues. Chest x-ray, brain magnetic resonance imaging, and body computed tomography scans are primarily used for the evaluation of metastatic disease, which usually occurs in the context of choriocarcinomas. Choriocarcinoma metastases are usually hypervascular and have a tendency to bleed, features that are reflected in their imaging appearance.
Article
Placental mesenchymal dysplasia is a benign condition that can be confused with a molar pregnancy by ultrasound scanning and gross examination. Conservative management should be considered with a normal-appearing singleton fetus and a cystic-appearing placenta. We present a case of placental mesenchymal dysplasia with a favorable outcome.
Article
Gestational trophoblastic disease encompasses a range of pregnancy-related disorders, consisting of the premalignant disorders of complete and partial hydatidiform mole, and the malignant disorders of invasive mole, choriocarcinoma, and the rare placental-site trophoblastic tumour. These malignant forms are termed gestational trophoblastic tumours or neoplasia. Improvements in management and follow-up protocols mean that overall cure rates can exceed 98% with fertility retention, whereas most women would have died from malignant disease 60 years ago. This success can be explained by the development of effective treatments, the use of human chorionic gonadotropin as a biomarker, and centralisation of care. We summarise strategies for management of gestational trophoblastic disease and address some of the controversies and future research directions.
Article
Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of beta-human chorionic gonadotropin (beta-hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low-resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2-year remission, a low rise in serum beta-hCG was observed. Transvaginal ultrasound revealed a well-circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental-site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers.
Article
The purpose of this study was to identify prognostic factors associated with development of gestational trophoblastic neoplasia (GTN) after hydatidiform mole (HM). A retrospective analysis of 189 patients with HM was performed. We recorded features such as maternal age, HM history, blood group, gestational age, uterine volume at evacuation, presence of theca lutein cysts, vaginal bleeding, and transvaginal ultrasonography with color Doppler imaging. We considered risk predictors to be the presence of nodules and hypervascularization within the myometrium or endometrium (positive ultrasound imaging). An univariate and multivariate analysis, with the COX nominal logistic model, was performed. Fourteen patients experienced GTN (7.4%). After univariate analysis, uterine size (P = .0139) and positive ultrasound results (P < .0001) were associated significantly with GTN development. At multivariate analysis, only positive ultrasound results maintained significance (likelihood ratio test: chi(2) = 0.0000). The risk of GTN is increased in patients with uterine involvement that is assessed by ultrasound imaging. None of the other prognostic factors that were evaluated was predictive of GTN development.
Article
To investigate the changes of the clinical features of hydatidiform mole. A total of 113 cases of hydatidiform mole treated in Peking Union Medical College Hospital during 1989-2006 were reviewed retrospectively, and a comparison was made to historic data from 1948-1975 using the chi2 test. The median age was 28 years (range, 20-55). The median gestational age was 90.2 days. Vaginal bleeding remains the most common presenting symptom, occurring in 94 of 113 cases (83.2%). Of 113 cases, 52 (46%) presented with excessive uterine size. Preeclampsia, hyperemesis, hemoptysis and theca lutein cysts occurred in 4 of 113 (3.5%), 12 of 113 (10.6%), 4 of 113 (3.5%) and 19 of 113 cases (16.8%), respectively. The incidence of postmolar trophoblastic neoplasia was 21% (24 of 113). Compared to historic data, the incidence of vaginal bleeding and preeclampsia were statistically lower (p < 0.005). The incidence of postmolar gestational trophoblastic neoplasia was increased moderately without statistical significance compared to historic data. Because of the wide use of ultrasonography and serum human chorionic gonadotropin test, current patients with hydatidiform mole have been diagnosed earlier in gestation and the clinical features have changed. Patterns of medical practice should be changed as well.
Article
We undertook a study to determine whether partial hydatidiform mole could be distinguished from other cases of first-trimester missed abortion using ultrasound. Scans from 22 cases of pathologically proved partial hydatidiform mole and 33 cases of first-trimester missed abortion were independently reviewed by three radiologists, each unaware of the final pathologic diagnosis. Using a standard data form, each radiologist recorded the dimensions, shape, and contents of the gestational sac, the sonographic appearance of the decidual reaction/placenta and myometrium, and the presence or absence of adnexal cysts. The following two criteria were found to be significantly associated (P less than .05) with the diagnosis of partial mole: 1) ratio of transverse to anteroposterior dimension of the gestational sac greater than 1.5, and 2) cystic changes, irregularity, or increased echogenicity in the decidual reaction/placenta or myometrium. There was high interobserver correlation for both criteria, as measured by the kappa statistic. In 50% of the cases, either both or neither of these criteria were met. When both criteria were met, the frequency of partial mole was 87%; when neither criterion was met, the frequency of missed abortion was 90%. These results indicate that ultrasound can be of value in predicting a high likelihood of partial mole prior to curettage.
Article
Although commonly encountered in spontaneous abortions, triploidy is rarely seen in fetuses surviving beyond mid-pregnancy. Mid-trimester sonographic findings in three triploid fetuses are described and compared with those reported in six prior cases. While sonographic characteristics are variable, common features include: 1) second trimester-onset fetal growth retardation with a reduced growth potential pattern of anthropometric growth, 2) body asymmetry with relative macrocephaly and an elevated head:abdominal circumference ratio, 3) hydrocephalus, 4) oligohydramnios, and 5) an abnormally large and/or hydropic placenta (in cases of paternal origin). Genetic amniocentesis and amniotic fluid chromosome studies should be performed when ultrasound findings suggestive of fetal triploidy are identified.
Article
Three women with gestational trophoblastic disease were examined using transvaginal color Doppler at the initial diagnosis and after each course of chemotherapy. In all cases, the examination before chemotherapy revealed hypoechoic areas surrounded by irregular echogenic areas and numerous intramyometrial flow signals. Pulsed Doppler examination revealed a low pulsatility index (PI) in the uterine arteries. After the completion of chemotherapy, a decrease in the vascularity and increase in the PI of the uterine arteries were demonstrated in two cases. These findings were closely consistent with the decrease in serum levels of beta-human chorionic gonadotropin. However, in the patient who developed permanent arteriovenous communication, hypervascularity persisted and the PI of the uterine arteries remained low, even after clinical remission was achieved. The present study indicates that transvaginal color Doppler ultrasonography is useful for the evaluation of gestational trophoblastic disease, both at the time of diagnosis and after chemotherapy.
Article
Uterine morphology assessed by transvaginal ultrasound and the hemodynamics of intratumoral vessels assessed by color Doppler ultrasound were prospectively correlated with the clinical outcome of 25 patients with trophoblastic tumors. Twenty patients were followed without treatment (observation group) and 16 achieved complete local resolution. The four subjects with local persistence were combined with five patients referred from other institutions and received chemotherapy (treatment group). In the observation group both techniques had 100% accuracy in predicting local resolution or local persistence. Persistence was predicted 1–3 weeks before the increase of β-human chorionic gonadotropin (β-hCG) levels, whereas resolution was observed up to 8 weeks before the disappearance of β-hCG. In one patient normal uterine morphology and vascularization in the presence of elevated hCG levels was associated with extrauterine spread. In the treatment group, normal uterine ultrasound morphology and negative color Doppler results had 100% negative predictive value. False-positive results were observed in two cases. We conclude that ultrasound evidence of abnormal uterine morphology or persistent vascularization on color Doppler examination with persistent hCG levels is indicative of local persistence. Normal uterine morphology with negative color Doppler results may be associated with extrauterine spread. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology
Article
Weekly serum beta-hCG measurements and transvaginal ultrasound scans coupled with color Doppler flow were performed on 8 patients with hydatidiform mole. Two patients later developed persistent trophoblastic disease, necessitating chemotherapy. The correlation coefficients between Doppler flow indices, systolic-diastolic (S/D) ratio and pulsatility index (PI) with log beta-hCG were -0.96 and -0.97, respectively. The weekly S/D and PI indices were plotted on an individual curve. Only the 2 patients who developed persistent gestational trophoblastic disease had PI index levels of < or = 1.5 as early as 2 weeks after molar evacuation. At that stage their serum beta-hCG levels were not different from some of the other patients. In this preliminary report, the regression of the disease could be reliably assessed by observing the changes in low resistance flow which paralleled the gradual decrements in serial beta-hCG levels. Thus, the contribution of this noninvasive imaging technique encourages the authors to further investigate Doppler flow monitoring among a larger sample of patients suffering from various gestational trophoblastic diseases.
Article
To analyze the results of prenatal findings and the outcome of triploidy and to organize an efficient approach to prenatal diagnosis during the second trimester. We reviewed 70 cases of triploidy presenting between 13 and 29 weeks' gestation over a 10-year period. Each fetus had at least one measurement below the normal range, and 50 cases (71.4%) presented with asymmetrical growth restriction and normal placental appearance. All cases of triploidy associated with partial mole were diagnosed before 25 weeks. Structural fetal defects were observed antenatally in 65 (92.9%) cases. The most common defects were abnormalities of the hands (52.3%), bilateral cerebral ventriculomegaly (36.9%), heart anomalies (33.8%), and micrognathia (26.2%). The most frequent combination of abnormalities was malformation of the hands and ventriculomegaly. Decreased red blood cell counts and high mean cell volume were found in the 50 cases tested. Vaginal bleeding in the first or second trimester was the most common maternal symptom reported. The major features that should alert the sonographer to the possible diagnosis of triploidy are partial molar changes or severe asymmetrical fetal growth restriction in the presence of an apparently normal placenta.
Article
Color Doppler sonography has replaced pelvic arteriography as well as real-time ultrasound in the assessment of patients with gestational trophoblastic disease. In about 25% of patients in whom human chorionic gonadotropin (hCG) levels are suggestive of trophoblastic disease, there will be no evidence of abnormal vessels in the uterus. In these cases it is assumed that hCG was produced by metastatic lesions. We present here three cases in which color Doppler examination was negative and where myometrial biopsies containing tumor were obtained by means of hysteroscopy. The fact that color Doppler, in its present form, does not detect small areas of trophoblastic tumor might also have implications for other kinds of tumors. Knowledge of the exact microscopic diagnosis in molar patients with persistent disease may have an impact on management.
Article
The objective of this study was to investigate the role of ultrasound in the differential diagnosis and management of early pregnancies presenting with placental molar changes. Placental features were recorded over a 10-month period in women undergoing ultrasound examination at 10-14 weeks of gestation. In cases of a molar pregnancy, the fetal karyotype was obtained in utero and, if the pregnancy continued, the maternal concentration of human chorionic gonadotropin (hCG) and uterine artery resistance to flow were measured serially. A histopathological examination of the placenta was performed in all cases after delivery. During the study period, 9425 women had an early scan and 11 molar pregnancies were identified including one classical mole, four hydatidiform moles coexisting with a normal pregnancy, three partial triploid moles and three partial moles associated in one case with a fetus presenting congenitial anomalies diagnostic of Beckwith-Wiedemann syndrome. The hCG levels were high in all cases except one case of triploidy and remained high during the rest of the pregnancy in cases of hydatidiform moles coexisting with a fetus. In these cases, the uterine artery resistance was normal. The present data indicate that placental ultrasound examination can correctly identify molar changes in early pregnancy and together with hCG level and uterine Doppler measurements can establish the differential diagnosis in utero of the various forms of placental molar transformations.
Article
Our purpose was to investigate the role of ultrasonography and maternal serum human chorionic gonadotropin in the early prenatal diagnosis of triploid pregnancies. A retrospective study on 61,314 consecutive singleton pregnancies examined by ultrasonography at 10 to 14 weeks' gestation was performed to identify the prenatal features of those complicated by triploidy. When available, the serum human chorionic gonadotropin level was measured and ascertained retrospectively. Cases lost to follow-up or for which no karyotype was available were excluded from the final analysis. Overall there were 18 cases of triploidy identified in a population of 58,862 singleton pregnancies, giving a prevalence of 1 in 3270. Fetal defects were observed in 8 (44.4%) of these cases; these included holoprosencephaly (n = 4), exomphalos (n = 3), and posterior fossa cyst (n = 1). In 6 (33.3%) cases the placenta showed molar changes. The fetal crown-rump length was below the 5th percentile in 10 of the 16 (62.5%) cases for which the menstrual age was also available. Fetal nuchal translucency thickness was above the 95th percentile in 12 (66.7%) cases, and the fetal heart rate was below the 5th percentile in 4 of the 13 (30.8%) cases evaluated. The maternal human chorionic gonadotropin level was high in 11 of the 13 (84.6%) cases tested, with similar distribution of the high values in molar and nonmolar triploidies. The combination of ultrasonographic examination of the fetoplacental features and measurement of the maternal serum level of human chorionic gonadotropin enables the diagnosis of most cases of triploidy at 10 to 14 weeks' gestation.
Article
To determine whether routine imaging using grey-scale ultrasound, pulse and color Doppler flow, endovaginal ultrasound and magnetic resonance imaging (MRI) provide information that significantly helps determine therapy in patients with nonmetastatic gestational trophoblastic disease. A literature search was performed to seek all publications in English and German that reported on investigations of imaging by ultrasound and MRI in patients with a diagnosis of trophoblastic tumor without evidence of metastases. Studies performed to make a diagnosis of hydatidiform mole were excluded. Included were studies that investigated the clinical usefulness and efficacy of these imaging methods in the diagnosis of invasive mole as a visual confirmation of the diagnosis based on human chorionic gonadotropin (hCG) and histology. Furthermore, the usefulness and efficiency of imaging in determining the effectiveness of chemotherapy were investigated. Analysis of these reports showed that lesions are detectable by imaging modalities at relatively high levels of hCG but may not be visualized at lower levels of hCG, when chemotherapy is nevertheless indicated and the diagnosis of neoplasia is fully justified. Moreover, myometrial lesions have been observed by MRI in patients who subsequently achieved spontaneous resolution of their disease without chemotherapy. At lower levels of hCG (< 700 mIU/mL), intramyometrial lesions may not be visualized by either ultrasound or MRI. Myometrial abnormalities may persist with resolution of the tumor. Thus, the sensitivity of either method is no better than 70% and the specificity is even lower. Weekly serial levels of serum hCG remain the most accurate, reliable and definitive arbiter of treatment management. Pelvic ultrasound or MRI need not be an integral part of pretreatment assessment. Imaging techniques are expensive yet not decisive in managing nonmetastatic trophoblastic disease. This finding applies to nonmetastatic disease only. With metastases, ultrasound, MRI and computed tomography do play an integral role in diagnosis, staging and management.
Article
To report the clinical features, management, and outcome of twin pregnancies consisting of a complete hydatidiform mole and a coexisting normal fetus. Between 1966 and 1997, seven women with complete hydatidiform mole and coexisting normal fetus were treated at the John I. Brewer Trophoblastic Disease Center of Northwestern University Medical School. Clinical features, including presenting symptoms, gestational dates, hCG levels, and complications, as well as route of delivery or evacuation, pregnancy outcome, genetic analysis, and need for chemotherapy were assessed. Four women required uterine evacuation before 20 weeks' gestation because of vaginal bleeding or medical complications, one woman required an emergency hysterotomy because of hemorrhage at 24 weeks, and two women delivered normal, viable infants at 26 and 34 weeks. The pathologic diagnosis of complete hydatidiform mole was confirmed in each case and the chromosome complement was 46,XX in all molar gestations. Four of seven women required chemotherapy for treatment of nonmetastatic gestational trophoblastic tumors, including both women who delivered viable infants and two of the five women whose pregnancies were evacuated before 24 weeks' gestation. All four patients were treated with five to seven cycles of a 5-day methotrexate regimen and achieved complete remission. Patients with a twin pregnancy consisting of a complete mole and a normal fetus are at increased risk for hemorrhage and medical complications, as well as the development of persistent gestational trophoblastic tumor.
Article
Complete hydatidiform moles are now being diagnosed earlier in gestation, thus the clinical presentation and pathologic findings of complete molar pregnancy have changed. We studied the sonographic appearance of first trimester moles and the ability of ultrasound to detect them. We reviewed the sonographic interpretation and sonograms, when available, from all patients with first trimester complete moles diagnosed at our institution from January 1988 to March 1996. Of the 24 patients in our study, the mean gestational age at time of the sonogram was 8.7 +/- 2.0 weeks (mean +/- SD) with a range of 5.7-12.3 weeks. The initial sonographic interpretation was a complete mole in 17 (71%) cases, partial mole versus failed pregnancy in two (8%), and failed pregnancy in five (21%) cases. Of the 22 patients with sonograms available for review, interpretation on review of the images was a complete mole in 18 (82%) cases, partial mole versus failed pregnancy in one (5%), and failed pregnancy in three (14%) cases. The typical sonographic appearance of a first trimester complete mole was a complex, echogenic, intra-uterine mass containing many small cystic spaces. The majority of first trimester complete moles demonstrate a typical ultrasound appearance such that the diagnosis can be made with ultrasound in most cases.
Article
Early ultrasound examination is being used increasingly in the diagnosis of molar pregnancy. The aim of this study was to examine the diagnostic implications of routine ultrasound examination for histologically confirmed molar pregnancies. This was a retrospective review of sonographic and histological findings in a series of consecutive cases referred to the National Trophoblastic Disease Surveillance Centre with suspected molar pregnancies. In 194 cases referred to the center over a 6-month period in whom results of a preceding ultrasound examination were documented, review of ultrasound findings and final histological diagnosis was carried out. There were 155 cases with a reviewed histological diagnosis of complete or partial hydatidiform mole. In 131 (67%) cases, the sonographic diagnosis was that of a missed miscarriage/anembryonic pregnancy with no documented suspicion of molar pregnancy, referral being on the basis of histological examination of products of conception. In 63 cases, ultrasound examination suggested molar pregnancy; in 53 (84%) of these, the diagnosis of molar pregnancy was correct. Overall, 37 of 64 (58%) complete moles had sonographic evidence of molar pregnancy compared to 16 of 91 (17%) partial moles. Of 155 histologically confirmed complete or partial hydatidiform moles, only 53 (34%) were suspected as molar sonographically. The majority of cases of molar pregnancy now present as missed miscarriage/anembryonic pregnancy sonographically, highlighting the importance of histological examination to diagnose gestational trophoblastic disease.
Article
We assessed 77 twin pregnancies, comprising complete hydatidiform mole (CHM) and healthy co-twin, to ascertain the risks to the mother and baby of continuing the pregnancy, versus termination. 24 women with histologically confirmed CHM and healthy co-twin pregnancies decided to have a termination. 53 women continued with their pregnancies, though two had to have terminations because of severe pre-eclampsia, and 23 spontaneously aborted (<24 weeks' gestation). 28 pregnancies lasted 24 weeks or more, resulting in 20 livebirths. Chemotherapy to eliminate persistent gestational trophoblastic disease (pGTD) was required in three of 19 women (16%; 95% CI 3-39) who terminated their pregnancies in the first trimester, and in 12 of 58 (21%; 95% CI 11-33%) who continued their pregnancies. CHM and healthy co-twin pregnancies have a high risk of spontaneous abortion, but about 40% result in livebirths, without significantly increasing the risk of pGTD.
Article
Ten women, referred because of a strong suspicion of gestational trophoblastic neoplasia, were examined by abdominal real-time ultrasound and color Doppler. The results were compared to those of pelvic angiography. In all but one case color Doppler examination revealed areas of increased vascularity. In all cases the findings of color Doppler and pelvic angiography agreed. Real-time ultrasound failed to detect abnormal uterine echoes in three of the patients where the other methods indicated tumor. The present study indicates that color Doppler could be of great value in a non-invasive assessment of trophoblastic tumors.