This is a case of a 33-year-old, G3P3(3003) female patient with a clinical presentation of vaginal bleeding associated with on and off hypogastric pain. The patient was diagnosed and managed as a case of tubo-ovarian abscess and subsequently underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO). Microscopic sections of both ovaries, however, showed dual population of tumor cells composed of medium-sized, mononucleated cells admixed with multinucleated giant cells with marked pleomorphism, extensive hemorrhage and necrosis. Immunohistochemistry studies using beta-hCG was diagnostic of ovarian choriocarcinoma, favoring non-gestational in origin. Classification of non-gestational choriocarcinoma (NGOC) was established using diagnostic criteria for NGOC established by Saito et al., and Mangla et al. DNA analysis, however, remains to be the gold-standard for differentiating between gestational (GOC) and non-gestational (NGOC) etiology.

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.

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

Female ; Humans ; Endodermal Sinus Tumor/pathology* ; Adenocarcinoma/pathology* ; Choriocarcinoma/pathology*

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

Hydatidiform mole coexistent with a live fetus (CMCF) is a rare entity occurring in 1:20,000 to 1:100,000 pregnancies. Three mechanisms of this type are possible: (1) a singleton pregnancy consisting of partial mole with a triploid fetus, (2) a twin gestation consisting of an androgenic complete hydatidiform mole with a biparental diploid fetus, and (3) a twin gestation consisting of a biparental diploid fetus with a normal placenta and a partial hydatidiform mole (PHM) with a triploid fetus. The abnormal triploid fetus in a partial mole tends to die in the first trimester while the fetus coexisting with a complete or partial mole in the dizygotic twin pregnancy has a chance to survive. Early detection and diagnosis of a molar gestation with a viable fetus is needed to allow medical interventions, if available. Three cases of complete mole with a twin fetus (CMTF) that were diagnosed in the prenatal period by ultrasonography will be presented. This report will also discuss the indications for continuing the pregnancy, and review the literature on the recommended prenatal care, intrapartum management, and postpartum surveillance. This report aims to encourage others to document cases of CMTF in order to arrive at a consensus regarding its optimal management.
Hydatidiform Mole ; Pregnancy, Twin

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

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