BACKGROUND

Since the advent of chemotherapy, cure rates for gestational trophoblastic neoplasia (GTN) have improved significantly. With increased survival, patients must cope with long-term sequelae of their treatment, including early menopause. Unlike natural menopause, treatment-induced menopause may cause a sudden and dramatic decline in estrogen, which can lead to more severe symptoms.

This study aimed to evaluate the prevalence of menopausal symptoms among young GTN survivors and to determine the impact of these symptoms on their health-related quality of life (QoL).

Ninety GTN survivors (RESULTS

A total of 90 patients were enrolled in the study with a mean age of 33.06 years. Majority (81.1%) reported at least one menopausal symptom. The most prevalent symptoms were psychological symptoms, followed by somatic, then urogenital problems. Among those with an intact uterus, 8.2% reported permanent amenorrhea. Only Stage III/IV and the presence of total hysterectomy were significantly associated with menopausal symptoms. The presence of menopausal symptoms was significantly associated with poorer health-related QoL among the respondents.

Menopausal symptoms are prevalent among young GTN survivors, and these negatively affect their health-related QoL. Emphasis should be placed on recognizing and addressing these symptoms. Adjunctive procedures, especially hysterectomy, should be carefully considered because these are significantly associated with menopausal symptoms.

Objectives: This study aimed to determine the clinical outcomes of ultra high-risk gestational trophoblastic neoplasia (GTN) patients managed with and without induction chemotherapy in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital. Methods: Clinical and demographic data were collected retrospectively from ultra high-risk GTN patients admitted in the Division of Trophoblastic Diseases, Department of Obstetrics and Gynecology, Philippine General Hospital from January 2015 to December 2021. Rate of remission and early death of those who received induction chemotherapy were compared to those who did not. Results: A total of 21 patients with ultra high-risk GTN were included in the study, nine of whom underwent induction chemotherapy while 12 had no induction chemotherapy and was given the standard EMACO regimen. There was no significant difference in the rate of early death as well as the rate and time to achieve remission between those who received induction chemotherapy compared to those who were immediately started on EMACO. Conclusion A firm conclusion cannot be drawn from the results considering the small population included in the study. Further studies with larger sample size and prospective study design are recommended.
Induction Chemotherapy ; Gestational Trophoblastic Disease

This is the first reported case of the use of immunotherapy in chemo-resistant Gestational Trophoblastic Neoplasia (GTN) in the country. A 41-year-old, Gravida 4 Para 3 (3013) with a diagnosis of GTN, Stage III: WHO risk score of 13 (Choriocarcinoma) was initially managed with 10 cycles of multiple agent Etoposide, Methotrexate, Actinomycin D- Cyclophosphomide and Vincristine (EMACO) and 19 cycles of Etoposide, Cisplatin- Etoposide Methotrexate and Actinomycin D (EP-EMA). With continuous rise in beta human chorionic gonadotropin (ßhCG) levels, the patient was referred to a Trophoblastic Disease Center where there was note of tumor progression to the brain. She was started on third-line salvage chemotherapy of Paclitaxel and Carboplatin (PC) with concomitant whole brain irradiation completing three cycles after which chemoresistance was again diagnosed with increasing hCG titers and increase in the number and size of the pulmonary masses which were deemed unresectable. Immunotherapy was started with Pembrolizumab showing a good response with marked fall in ßhCG levels. The onset of immune-related adverse events (irAEs) caused a marked delay in subsequent cycles of immunotherapy. With management of the irAEs, two more cycles of Pembrolizumab with fifty percent dose reduction were given with corresponding drop in ßhCG levels. However, the patient subsequently developed gram-negative septicemia with possible hematologic malignancy and finally succumbed to massive pulmonary embolism. The case highlights the importance of prompt diagnosis and referral to a Trophoblastic Disease Center and the use of immunotherapy in chemo-resistant GTN.
Gestational Trophoblastic Disease ; Choriocarcinoma ; Pembrolizumab

Background: During postmolar evacuation surveillance, beta-human chorionic gonadotropin (β-hCG) regression levels can predict invasive disease while Doppler ultrasound can assess in vivo tumor neovascularization and quantify uterine blood supply. As an ancillary tool to β-hCG monitoring, ultrasound can detect the early presence of viable trophoblastic tissues and identify patients at risk of developing postmolar gestational trophoblastic Neoplasia (PMGTN). Objective: The objective of this study was to correlate uterine artery Doppler ultrasound with β-hCG levels during pre- and postmolar evacuation surveillance among patients with complete mole. Materials and Methods: A cohort of patients with sonographic diagnosis of complete hydatidiform mole and managed with suction curettage in the same institution were prospectively followed up after evacuation. The pre- and postmolar evacuation surveillance period was at days 1, 7, 14, 21, 28, and 35. Monitoring of serum β-hCG levels was based on the standard regression curve. For Doppler ultrasound parameters, monitoring of the systolic/diastolic (S/D) ratio, pulsatility index (PI), resistance index (RI), and peak systolic velocity (PSV) was based on its relationship with its serum β-hCG levels. The ultrasound images generated were archived and reviewed by the authors. Descriptive and inferential statistics were utilized to analyze median differences. For the correlation of uterine artery Doppler flow parameters, analysis for the test of difference used Pearson correlation and multiple linear regression analysis for the odds ratio. Results: Sixteen of the 23 enrolled patients completed the protocol (16 of 23, 69.50%). A majority had spontaneous remission (13; 81%) while 3 cases (19%) presented increasing and plateauing β-hCG levels. The pre- and post evacuation median β-hCG levels showed a significant decrease (P = 0.001). As post evacuation β-hCG levels decreased, PSV also decreased (r = 0.478, P = 0.061) while Doppler parameters, RI, PI, and S/D ratio increased. However, when post evacuation β-hCG levels rose or plateaued, Doppler parameters decreased. These changes had statistical correlation (all P < 0.05). Moreover, the magnitude of the relationship for β-hCG and Doppler parameters was moderate and ranged from 0.524 to 0.581. Among the Doppler parameters, the S/D ratio and RI of the right uterine artery strongly predicted a rise in β-hCG levels. The odds ratio of predicting increased β-hCG levels and risk of gestational trophoblastic neoplasia by the right S/D ratio were − 2683.67 (confidence interval [CI] = −271.692–5095.655; P = 0.034) and by the right RI − 66,193.34 (CI = −161,818.107–29,431.433; P = 0.046). Notably, Doppler parameter changes appeared early at day 14 up to day 35 and before the appearance of abnormal β-hCG regression patterns. Conclusion There is a strong correlation between uterine artery Doppler flow changes and β-hCG levels during postmolar evacuation surveillance. The inverse relationship of the S/D ratio, PI and RI, and β-hCG regression patterns confirms spontaneous remission of the disease. For patients with abnormal β-hCG patterns, this relationship is altered. The Doppler changes become erratic, unpredictable, and significantly decreased. These changes were detected as early as 2 weeks post evacuation. Thus, the use of ultrasound as an adjunct to β-hCG post evacuation surveillance can predict abnormal β-hCG regression patterns and identify patients at risk of developing postmolar gestational trophoblastic neoplasia (PMGTN).
Hydatidiform Mole ; Gestational Trophoblastic Disease ; Hydatidiform Mole

Introduction: Obstetrical hemorrhage remains to be one of the most common causes of maternal morbidity and mortality. Postpartum hemorrhage occurs after delivery and is usually secondary to uterine atony, genital tract lacerations, and retained placental fragments. Case: A case of a 21-year old, primipara, presented with profuse vaginal bleeding and hemoptysis at 3 weeks' postpartum. A clinical diagnosis of gestational trophoblastic neoplasia was established after an elevated serum beta human chorionic gonadotropin was obtained and an intrauterine mass was seen on ultrasonography, including metastasis to the lungs and liver seen through imaging studies. Discussion Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin (EMACO) is the mainstay treatment for Stage IV disease. However, complications such as hemorrhage and tumor rupture are best managed surgically. Although rare, a diagnosis of choriocarcinoma should be considered in patients with persistent bleeding after a normal pregnancy to institute proper management and avoid associated complications of tumor progression.
Choriocarcinoma ; Gestational Trophoblastic Disease ; Postpartum Hemorrhage

Placental site trophoblastic tumor (PSTT) with uterine arteriovenous malformation (AVM) is a rare and potentially catastrophic occurrence. A high index of suspicion and immunohistochemistry secured the diagnosis. The use of appropriate imaging modalities led to the identification of the extent of the disease. Sequential planned management from neoadjuvant intensive chemotherapy, bilateral uterine artery embolization, and laparotomy, and coordinated among different medical disciplines resulted to a successful definitive treatment. Due to its relatively chemoresistant nature, hysterectomy is the mainstay of treatment. Adjuvant platinum-based intensive chemotherapy has been shown to improve overall survival in patients with metastatic disease and those with poor prognostic factors. This case of PSTT with a typical clinical profile was noteworthy due to the development of a significant AVM, a rare complication of PSTT. This case report included a review of treatment experiences as well as peculiarities that set PSTT apart from the more common gestational trophoblastic diseases.
Gestational Trophoblastic Disease ; Trophoblastic Tumor, Placental Site

Precision medicine is a form of medicine that utilizes information about a person’s own genes to prevent, diagnose, or treat disease. In trophoblastic disease, precision medicine is important for accurate diagnosis, risk stratification, prognostication, and management. Immunohistochemistry, particularly p57kip2, has become an important ancillary procedure for the accurate identification of complete hydatidiform mole (HM). Molecular genotyping, on the other hand, is now considered the gold standard for the accurate classification of HM. Both tests are important for prognostication and the determination of the appropriate follow‑up plan. For gestational trophoblastic neoplasia, immunohistochemical markers can confirm the histologic diagnosis of its various types. Molecular genotyping differentiates gestational from nongestational tumors with overlapping histology and allows for precise identification of the index or causative pregnancy of a choriocarcinoma.
Gestational Trophoblastic Disease ; Hydatidiform Mole ; Precision Medicine

Objective: Despite the widespread use and measurement of beta‑human chorionic gonadotropin (β‑HCG) among hydatidiform mole (HM) patients, models derived from this biomarker to predict the remission or postmolar gestational trophoblastic neoplasia (GTN) rarely perform well. The study aimed to generate cutoff points for postevacuation β‑HCG levels and evaluate their performance among women with complete molar pregnancies Methods: A retrospective cohort study composed of women with complete HM underwent bivariate procedures comparing characteristics between the comparison groups. Cut points using Liu’s and Youden’s indices were estimated, and their performance was evaluated using receiver operating characteristic curve analysis. Cox regression to compare time‑to‑progression across these proposed β‑HCG cutoffs was also performed. Results: The incidence of postmolar GTN among the 155 women in the study was 15.5% (95% confidence interval: 10.2%–22.2%). Postevacuation HCG levels had a better prediction of disease status than preevacuation and HCG ratio models (χ2 : 163.07, P < 0.01). A cutoff at 508 mIU/mL the 3rd‑week postevacuation (area under the curve [AUC]: 0.89, sensitivity: 87.5%, specificity: 90.1%) was comparable with the 185 mIU/mL cutoff at the 5th‑week postevacuation (AUC: 0.89, sensitivity: 91.7%, specificity: 87%). The hazards ratio of postmolar GTN was 29.74 (8.53–103.71) and 39.89 (8.82–180.38) for the 3rd and 5th weeks HCG after evacuation adjusting for clinically relevant variables Conclusion The first 3rd‑ and 5th‑week postevacuation levels of β‑HCG demonstrated potential in predicting postmolar GTN. However, further refinement and adjustment for clinically relevant risk factors are still needed.
Choriocarcinoma ; Gestational Trophoblastic Disease ; Prognosis

Background: Gestational trophoblastic neoplasia (GTN) is considered one of the most curable malignancies, especially when diagnosis and treatment are commenced early. Identifying predictors for the development of GTN will enable prompt management equating to an excellent prognosis. Objectives: The objectives of this study were to determine the validity of uterine artery Doppler parameters (UADPs) as predictors for postmolar GTN, compare UADP values before and after evacuation, determine cutoff values and relationship with beta‑human chorionic gonadotropin (hCG) levels. Materials and methods: This was a prospective cohort study, which included histopathologically confirmed hydatidiform mole (HM) patients who underwent suction curettage. UADPs (pulsatility index (PI), resistive index, and systolic/diastolic [S/D] ratio) were measured preevacuation, 4 weeks postevacuation, and 6 weeks postevacuation. Patients were followed up to determine whether they will develop postmolar GTN or not. Results: A total of 31 HM patients were admitted during the study period, 84% (26/31) of whom underwent suction curettage. Of these, 92% (24/26) had histopathology of complete HM and were recruited. However, only 17 patients followed up and completed the study. Results showed that there was an increasing trend of the UADP from preevacuation to 6 weeks postevacuation and the trend between those with and without postmolar GTN was statistically significant. There was also an inverse relationship between the UADP and baseline β‑hCG values. UADP showed lower values among patients who developed postmolar GTN compared to those who did not. The cutoff values recommended by the area under curve (AUC) that can be a possible predictor were 4th‑week right PI of 2.14 (AUC = 0.71) and right S/D ratio of 2.60 (AUC = 0.73) and 6th‑week left PI of 2.80 (AUC = 0.70) and right PI of 2.53 (AUC = 0.74). Conclusion Neoangiogenesis, a hallmark of malignancy, is correlated with invasive disease and will show increased myometrial vascularization with lower uterine artery indices. Doppler ultrasound may be a useful tool for postmolar follow‑up and GTN diagnosis. However, the small sample size in this study is a limitation and a larger multicenter study is recommended.
Gestational Trophoblastic Disease ; Hydatidiform Mole

Background: Gestational trophoblastic neoplasia (GTN) presents as vascular mass of varying morphology on ultrasound and confirmed through quantitative serum β subunit human chorionic gonadotrophin (β‑hCG). In regions with limited access to β‑hCG, ultrasound plays a crucial role in the initial diagnosis for timely management. Objectives: This study aimed to investigate the associations between ultrasound vascular morphologic features, serum β‑hCG levels, and histopathology in GTN cases. Methodology: A cross‑sectional review was conducted on 113 cases with ultrasound impression of GTN over an 8‑year period. The patient data were extracted from case records, and ultrasound images were categorized based on the distinct features. Associations with β‑hCG levels and histopathology were analyzed using the Chi‑square test and Mann–Whitney U‑test. Statistical significance was set at P < 0.05. Results: A significant association was observed between ultrasound category and serum β‑hCG (P < 0.0001). The compact and diffuse types were more prevalent with β‑hCG levels between 104 to <105 mIU/mL, while the lacunar type was common among patients with ≥105 mIU/mL. However, there was no significant association between ultrasound categories and mean β‑hCG levels. Regarding histopathology, the lacunar type was more common in invasive moles, whereas the compact and diffuse types tended to be seen with choriocarcinoma, although these were not statistically significant (P = 0.182). Conclusions Morphologic types of GTN by gray scale and Doppler ultrasound vary across the different levels of serum β‑hCG and may suggest the histopathological diagnosis. This study provides valuable insights into the ultrasonographic characteristics of GTN, which can aid in its diagnosis and management.
Gestational Trophoblastic Disease ; Ultrasonography, Doppler