Uterine epithelioid trophoblastic tumor with the main manifestation of increased human chorionic gonadotropin:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotropin(hCG).This study reported a case of uterine ETT with the main manifestation being increased hCG.CASE SUMMARY A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022,complaining of increased hCG levels for 1 month.Magnetic resonance imaging revealed gestational trophoblastic tumor,and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed.The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results.Total laparoscopic hysterectomy and bilateral salpingectomy were performed,and hCG levels returned to normal.The patient was without recurrence during the postoperative 3-month follow-up.CONCLUSION This study reported a case of uterine ETT with the main manifestation being increased hCG,highlighting that ETT should be considered in the presence of abnormal hCG.A total laparoscopic hysterectomy is recommended.

Epithelioid trophoblastic tumor of the lower uterine segment and cervical canal:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT) is the rarest type of gestational trophoblastic tumor(GTT). It has been reported that more than 50% of ETTs arise in the uterine cervix or the lower uterine segment. Here, we report a case of ETT within the lower uterine segment and cervical canal and discuss its manifestations,possible causes, and related influencing factors.CASE SUMMARY A 35-year-old woman(gravida 7, miscarriage 3, induction 2 with 1 being twins,para 2 of cesarean section, live 2), who had amenorrhea for 9 mo after breastfeeding for 22 mo after the last cesarean section, was diagnosed with ETT. The lesion was present in the lower uterine segment and endocervical canal with severe involvement of the anterior wall of the lower uterine segment and the front wall of the lower uterine segment where the cesarean incisions were made.Laboratory tests showed slight elevation of serum beta-human chorionic gonadotropin. Intraoperative exploration showed the presence of a normal-sized uterus body with an enlarged tumor in the lower uterine segment. The surface of the lower uterine segment was light blue, the entire lesion was approximately about 8cm × 8 cm × 9 cm, with compression and displacement of the surrounding tissue.Histological examination diagnosed ETT. Immunohistochemical analysis showed positive expression of p63, with a Ki-67 proliferation index of 40%.CONCLUSION A search of the PubMed database using the search terms "cesarean section" and "epithelioid trophoblastic tumor" retrieved nine articles, including 13 cases of ETT and ETT-related lesions, all 13 cases had a history of cesarean section, and the lesions were all located at the cesarean section incision on the anterior wall of the lower uterine segment. The present case is the 14th reported case of ETT after cesarean section. Therefore, we deduced that cesarean section trauma had an important effect on the occurrence of ETT at this site.

Special epithelioid trophoblastic tumor:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT)is a special type of gestational trophoblastic tumor.However,its pathogenesis has been incompletely elucidated.ETT rarely occurs in the ovaries and fallopian tubes,unlike placental site trophoblastic tumor,requiring a histopathological biopsy and immunohistochemistry for further diagnosis.CASE SUMMARY A 29-year-old woman with irregular vaginal bleeding and elevated serum chorionic gonadotropin(β-hCG)levels presented similar symptoms to ectopic pregnancy.Transvaginal ultrasound revealed abnormal echoes of the left adnexa.Postoperatively,the pathology of the left ovary and fallopian tube was reported as ETT.The patient was followed up with regular hCG measurements and ultrasounds.The blood hCG values showed an upward trend 3 mo after the operation and then chemotherapy was prescribed.The current health status is normal.CONCLUSION For women of childbearing age with elevated serumβ-hCG levels,practitioners should consider ETT and be alert to the poor prognosis of the disease.After surgery,the patient’s condition should be closely observed to prevent recurrence and metastasis.Postoperative chemotherapy is only helpful for treating the disease to a certain extent.

Gestational Trophoblastic Neoplasia: Clinical and Therapeutic Profile in Madagascar

Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization. This includes complete and partial hydatidiform mole (HM) and gestational trophoblastic neoplasia (GTN). The aim of this study was to report the epidemiological, clinical and therapeutic profile of gestational trophoblastic neoplasia (GTN) over period of ten years in the department of Oncology Radiotherapy at the University Hospital Joseph Ravoahangy Andrianavalona (HJRA) Antananarivo Madagascar. Medical records of women diagnosed with GTD in the department of Oncology Radiotherapy at HJRA from January 1st, 2007 to September 2017 were retrospectively reviewed. Only patients with the FIGO diagnosis GTN were included, while those with the histological diagnosis of hydatidiform mole (HM), also sometimes classified as GTD, were not included in this study. Also excluded were all cases with incomplete or missing data. Twenty four patients were included. Median age of patients at the time of diagnosis was 37 years (range 18 - 60). Most patients developed GTN following molar pregnancy (75%), had disease duration from antecedent pregnancy of less than 6 months (58.20%), and had the pre-treatment hCG level more than 10,000 IU/L (58.27%). At diagnosis, 14 patients (58.33%) had localized disease (M0). Most common metastatic sites at initial diagnosis were the liver and brain (20.83%). After a median follow-up from initial diagnosis of six months (range 1 - 24), 58.33% were lost to follow up. This represented an increase in the percentage of patients lost to follow up prior to completion of therapy, when compared with our previous results for an earlier time period. GTN in Malagasy woman displays an aggressive clinic profile. Finding ways to increase treatment compliance provides the best way to minimize recurrences of this potentially deadly disease.

Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide

Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.

A COMPARATIVE STUDY OF TRANSVAGINAL ULTRASONOGRAPHY AND PELVIC ARTERIOGRAM IN ASSESSMENT OF PATIENTS WITH GESTATIONAL TROPHOBLASTIC TUMOUR

Objective:To compare the reliability of transvaginal ultrasonography with pelvic arteriography in the assessment of patients with gestational trophoblastic disease. Methods. Transvaginal ultrasonography was performed in 24 patients with gestational trophoblastic tumour. Within one week after ultrasound investigation, pelvic arteriography was carried out in each patient. Of 24 cases, 16 patients hadn’t been treated by chemical reagent, 5 had accepted 2 to 5 courses of chemotherapy, and 3 had achieved complete remission before both investigations performed. Results. In 3 patients with complete remission, 2 had no evidence of abnormal findings either on transvaginal ultrasonography or on pelvic arteriography, 1 showed intramyometrial lesions by both methods. In the remaining 21 patients, all demostrated a abnormal uterine image, and 5 of them accompanied with the finding of parametrium metastatic signs by transvaginal ultrasonography; these abnormal results were confirmed by pelvic arteriographic imaging. However, in two cases without clinical and ultrasonic signs of parametrium metastasis, pelvic arteriography indicated the early metastasis of parametrium ves- sels. Conclusions. Even though it is difficult to predict the early parametrium metastasis in patients with gestational trophoblastic disease by B-ultrasonic investigation, our data would support the introduction of transvaginal ultrasonography in the diagnosis and evaluation of gestational trophoblastic tumour.

THE ROLE OF HYSTERECTOMY IN THE THERAPY OF GESTATIONAL TROPHOBLASTIC TUMOR

To evaluate the role of hysterectomy for patients with gestational trophoblastic tumor. [WT5”BX]Methods.[WT5”BZ]We retrospectively analyzed 68 cases of gestational trophoblastic neoplasia treated by hysterectomy from 1985～1997 at PUMC hospital. Thirty eight cases were diagnosed of choriocarcinoma and 30 were invasive mole. [WT5”BX]Results.[WT5”BZ]Twenty three elder patients who didn’t desire to preserve fertility were selected for hysterectomy after shorter courses of chemotherapy, 22 of them had a complete remission(95 6%), the total aver age courses of chemotherapy was 4 2. Of twenty seven chemorefractory cases who were suspected of a refractory isolated lesion in the uterus, delayed hysterectomy as an adjunct to chemotherapy was performed, 20 of them got a complete remission(74 1%), the total average courses of chemotherapy were 9 4. Emergency hysterectomy is indicated in 18 patients with uterine perforation or life threatening hemorrhage, 17 cases had a complete remission(94 4%), the total average courses of chemotherapy were 7 6. [WT5”BX]Conclusion.[WT5”BZ]Although the development of effective chemotherapy has resulted in improved survival of patients with gestational trophoblastic tumor, hysterectomy remains an important adjuncts in the treatment of a selected subset of patients; in order to operate more completely and prevent recurrence, it’s better to perform extended hysterectomy for the indicated patients.

EXPRESSION OF P53 PROTEIN AND PROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROPHOBLASTIC DISEASE

To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

DIAGNOSIS AND TREATMENT OF THE MALIGNANT GESTATIONAL TROPHOBLASTIC TUMOR WITH PULMONARY METASTASIS COMPLICATED WITH PULMONARY TUBERCULOSIS

Objective. To evaluate the diagnosis and treatment for malignant gestational trophoblastic tumor(MGTT) with pulmonary metastasis complicated with pulmonary tuberculosis. Methods. To analyze ten cases of MGTT with pulmonary metastasis complicated with pulmonary tuberculosis in our hospital from 1980 to 1997 retrospectively. Results.From the x ray film, there are great resemblances between MGTT with pulmonary metastasis and pulmonary tuberculosis. Of 10 patients, 7 of them were examined out pulmonary tuberculosis during the chemotherapy of MGTT. Pulmonary tuberculosis appeared six months before chemotherapy in three cases. All of the patients were treated with multiagent chemotherapy. Seven patients achiceved a complete remission, 2 patients developed drug resistance and died of cerebral haemorrhage and cerebral herniation, 1 woman who had achieved a complete remission from MGTT for 14 months died of miliary tuberculosis. Conclusion. It is very important to make differential diagnosis of the MGTT with pulmonary metastasis complicated with pulmonary tuberculosis. Trying to avoid excessive anti tumor treatment owing to mistake pulmonary tuberculosis for pulmonary metastasis, and avoiding missing an opportunity of anti tuberculosis treatment because of missed diagnosis should be emphasized.

Expression of c-erbB2 in Gestational Trophoblastic Disease and Its Clinical Significance

Summary: In order to explore a potential indicator of predicting the occurrence and development of gestational trophoblastic tumor, the expression of c-erbB2 oncogene in human normal placenta, hydatidiform mole and choriocarcinoma was investigated. The expression of c-erbB2 was detected immunohistochemically by monoclonal antibody against the gene on the formalin-fixed paraffin sections of 21 hydatidiform moles, 21 invasive moles, 20 choriocarcinomas and 30 normal placentas. Results showed that the expression level of c-erbB2 was significantly higher in gestational trophoblastic tumor than in hydatidiform mole and normal placenta of midterm and term pregnancy (P<0.05), while there was no significant difference between patients with gestational trophoblastic tumor of stage Ⅲ, Ⅳ and those of stage Ⅰ, Ⅱ. It was demonstrated that overexpression of c-erbB2 may closely associated with malignant transformation of hydatidiform mole, not only providing important insight into pathogenesis of gestational trophoblastic tumor, but also having an important significance for the early diagnosis and early treatment of gestational trophoblastic tumor.

How and Why Do Gestational Trophoblastic Neoplasms Overproduce Human Chorionic Gonadotropin?

From the published data, the present mini-review attempts to answer two fundamental questions about the gestational trophoblastic neoplasms. In addition, it extrapolates the findings to other cancers that produce small amounts of hCG and how a novel therapies could be developed.

Illness Perception in Gestational Trophoblastic Disease Patients: How Mental Representations Affect Anxiety, Depression, and Infertility-Related Stress

Gestational Trophoblastic Disease encompasses a group of pregnancy-related disorders that derive from the placenta. Taking Leventhal’s Common Sense Model as a starting point, this study aims to investigate how illness perception could influence patients’ psychological adaptation to these rare diseases. Thirty-seven women completed: the Illness Perception Questionnaire-Revised, the Beck Depression Inventory Short Form, the State-Trait Anxiety Inventory, and the Fertility Problem Inventory. Results show that the perception of severe illness consequences significantly predicts the level of anxiety patients reported at the time of questionnaire completion. Furthermore, mental representations of illness present a significant association with infertility-related stress. Specifically, the belief in the efficacy of the treatment results in fewer feelings of discomfort and isolation from family and social context due to infertility-related problems. Since patients’ illness perception was found to have a specific impact on both anxiety and infertility-related stress, this variable should be considered in the planning of a clinical intervention.

EMA/CO Regimen Chemotherapy for Gestational Trophoblastic Tumor

Objective To evaluate the efficacy and safety of etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide (EMA/CO) therapy for gestational trophoblastic tumor (GTT). Methods Medical records of all patients with low risk, middle risk and high risk GTT receiving EMA/CO regimen chemotherapy were analyzed retrospectively. Results\ Twenty one low risk and fourteen middle risk GTT received EMA/CO with 100% remission, six patients with high risk GTT received EMA/CO with 83% complete response and with 17% partial response; Gastrointestinal, hematologic and hepatic toxicity, as well as shed of hair is predictable, mild and reversible. Conclusion\ At present EMA/CO chemotherapy is the choice of our treatment for patients with high, middle and low risk GTT.\;

Effect of Ephrin-A1/EphA2 on Invasion of Trophoblastic Cells

The effect of axon guidance factors ephrin-A1/EphA2 on the invasion of trophoblastic cells and the possible mechanism were investigated in this study. The expression of EphA2 in vascular endothelial cells was detected by immunohistochemistry. The proliferation and invasion of TEV-1 cells （an extravillous trophoblastic cell line） in first trimester were determined by cell counting kit-8 （CCK-8） and Transwell invasion assay. Real-time PCR was used to detect the expression ofephrin-A1 in TEV-I cells treated with EphA2 at different concentrations （10, 50, 100, 500, 1000 and 5000 μg/L）. The results showed： （1） EphA2 was expressed in the vascular endothelial cells; （2） EphA2 could promote the proliferation of TEV-1 cells. The proliferative capacity reached a peak in TEV-1 cells treated with 100 μg/L EphA2 （P〈0.05）; （3） EphA2 could increase the invasion of TEV-1 cells. The invasive ability was the greatest in TEV-1 cells treated with 500 pg/L EphA2 （P〈0.05）; （4） in the presence of EphA2 （0-500 μg/L）, the expression of ephrin-A1 was increased concentration-dependently （P〈0.05）, but when the concentration of EphA2 was over 500 μg/L, the expression of ephrin-A 1 ceased to increase （P〉0.05）. It was concluded that EphA2 can promote the invasion and proliferation of the human extravillous trophoblastic cells probably by regulating the ephrin-A1 ligand.

Expression of epidermal growth factor and its receptor in gestational trophoblastic diseases

Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.

Metastasia Lesion of Gestation Trophoblastic Tumor in Abdominopelvic Cavity Diagnosed by Sonographic and Doppler Imaging

Objective: The purpose of this study was to review clinical data of metastasia lesion of gestation trophoblastic tumor (GTT) in abdominopelvic cavity by color Doppler ultrasound. Subjects and Methods: A retrospective analysis of 13 cases of GTT in China was performed. Clinical appearances, serum human chorionic gonadotropin (hCG) levels, sonographic findings, Doppler waveforms, and patient outcomes were followed up. Color Doppler ultrasound was performed to diagnose the presence of GTT, detect metastasia lesion in abdominopelvic cavity, assess disease recurrence, and monitor the efficacy of chemotherapy. Results: Of the 13 patients with GTT, 4 had choriocarcinoma which 3 cases occurred after an abortion, 1 after a year of dilation and suction evacuation for the hydatidform mole. Metastasia lesion in abdominopelvic cavity was detected by color Doppler ultrasound in all cases of choriocarcinoma, among which the metastasia lesion were found at uterine fundus, near uterus, colon and cystic vascular space near the uterus, repectively. 9 cases with an invasive hydatidiforn mole (IHM) occurred after one to three months of dilation and suction evacuation for the hydatidform mole, consistant with the hCG levels markedly elevating. Metastasia lesion in abdominopelvic cavity was also detected by color Doppler ultrasound besides invasive lesion in uterine muscular layer in all cases of IHM, among which 3 cases showed metastasia lesion in cystic vascular space near the uterus, 2 cases were detected in side wall of pelvic cavity, while the rest were found in abdominal cavity, right kidney, colon and near uterus, respectively. Meanwhile, the image of metastasia lesion with IHM was similar to choriocarcinoma’s. And the reticular structure, the cystic vascular space and solid lesion may be showed by ultrasound. The metastasia lesion had abundant flow. Doppler waveforms showed resistive indices of 0.34 (SD 0.07) for metastasia lesion. There was the same lower-impedance as invasive lesion in uterine muscular layer. Except an IHM with the renal metastasia lesion having been followed, abnormal sonographic and Doppler findings in other metastasia disease all disappeared after surgical operation or chemotherapy were successful. Conclusions: Sonography and Doppler imaging were helpful in detecting metastasia lesion in abdominopelvic cavity, and in following the effectiveness of chemotherapy. And it should be taken full examination for GTT by Color Doppler ultrasound in order to avoid mistake.

Macroscopic hematuria as a presentation of gestational trophoblastic neoplasia in an adolescent woman

Gestational trophoblastic neoplasia (GTN) is a hemorrhagic malignancy with highly rapid potential metastasis via hematogenous spreading. Renal metastasis is of infrequent occurrence. Among previous case reports of renal metastasis in GTN, this is the youngest woman presenting a large renal lesion concurrent with pulmonary and brain metastases. Disease remission had been achieved by treatment with combined chemotherapy and whole brain radiation, although acute myeloblastic leukemia (AML) developed later.

A rare cause for gestational trophoblastic neoplasia: Placental site trophoblastic tumor

Placental site trophoblastic tumor is a rare sub-group of gestational trophoblastic neoplasia. There is a wide clinical spectrum of presentation and behaviour ranging from a benign condition to an aggressive disease with a fatal outcome. We report a case of placental site trophoblastic tumor in 23-year-old women with irregular vaginal bleeding during postpartum lactation period. In addition to persistent low level β-hCG titers, ultrasound examination revealed a suspicious low-echoic area in the myometrium consistent with gestational trophoblastic disease. After histopathological examination of the specimen achieved by ultrasound-guided dilatation and curettage of the uterus, the placental site trophoblastic tumor diagnosis was made and subsequently total abdominal hysterectomy was performed. The patient had an uneventful recovery, and no recurrence was detected for 40 months in the follow-up period.

Possible link between congenital uterine malformations and epitheliod trophoblastic tumor

Background: Epitheloid trophoblast tumor (ETT) is a tenuous type of gestational trophoblastic disease. Although clinically ETT behave in variable fashion, it is considered as a potentially malignant tumor, fatal malignancy occurs in 10% of the cases. Case and Conclusion: A 41 years old patient, who previously underwent Tompkins operation because of congenital uterine septum was admitted to our clinic due to irregular bleeding. Despite of serum hCG levels under the upper limit of normal, histopathology analysis of D&C obtained endometrial samples confirmed the presence of ETT by immunostainings. Henceforth we performed prompt abdominal hysterectomy and preserved the normal structured ovaries. According to the müllerianosis theory of endometriosis aberrant differentiation or migration could cause spreading of cells throughout the fetal organogenesis of the uterus. These cells in an apoptosis week environment might correlate with the initiation of ETT. As a conclusion we suggest further studies to assess the link between ectopic cells and ETT, to gain a better understanding in the pathomechanism of the tumor.

Doppler Ultrasound in Post-Molar Gestational Trophoblastic Neoplasia

Objectives: To evaluate the role of Doppler ultrasound in prediction and follow up during management of gestational trophoblastic neoplasia (GTN). Methods: The study was performed at Oncology Unit, Maternity Hospital, Ain Shams University in the period from November 2015 to December 2018. Forty cases of complete mole, after evacuation and follow up of serum human chorionic gonodotrophin (β-hCG) titre until it reached zero level (group I) and forty post molar GTN cases (group II) were included in the study. Doppler ultrasound of the subendometrial and intramural blood flow was done for all cases of group I and II. Doppler included two dimensional and three dimensional power Doppler indices. Group II received Methotrexate (MTX) and folinic acid in a dose of 8-day MTX-FA regimen. Doppler follow up for six months of group II concurrently with the chemotherapy regimen was done. Results: A statistically significant difference was found between group I and II regarding initial readings of all Doppler parameters. Follow up for 6 months of GTN cases revealed progressive statistically significant decrease of intramural and subendometrial three dimensional power Doppler (3DPD) indices, while there was a significant increase in two dimensional (2D) Doppler parameters. Four cases were resistant to Methotrexate chemotherapy. Cut off values were determined for prediction of GTN. Multivariate analysis revealed that the most predictive parameter was the subendometrial pulsatility index (PI), odds ratio = 10.63 (95% CI: 1.30 - 86.89). The cut-off point for sub-endometrial PI was: 2.05 (AUC, 90%;sensitivity, 88%;specificity, 76%, PPV 78%, and NPV 86%) with a diagnostic accuracy of 87%. To and Fro sign may be considered a pathognomonic intramural ultrasound sign for prediction of GTN chemo-resistance or choriocarcinoma. Conclusion: Cut off values for Doppler parameters can be used for early predication of GTN. Doppler ultrasound indices can be used during follow up of GTN cases concurrently with serum β-hCG to monitor the response to treatment.