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

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

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

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

Gestational trophoblastic diseases are histologically different types of tumors originating from the placenta with an incidence of 0.2–5.8/1000 pregnancies. Ectopic pregnancy is the implantation of the fertilized ovum outside the uterine cavity, and a 0.64% incidence is reported. Ectopic cornual pregnancy and molar pregnancy are rare cases, and a combination of these two rare entities occurring simultaneously is even rare and very few cases have been reported in the literature. A cornual pregnancy refers to the implantation and development of a gestational sac in one of the upper and lateral portions of the uterus, whereas an interstitial pregnancy is a gestational sac that implants within the proximal, intramural portion of the fallopian tube that is enveloped by the myometrium. We present one of the rare combinations of molar pregnancy and cornual/interstitial ectopic pregnancy in a 30‑year‑old G3 P1 who presented with a triad of amenorrhea, vaginal bleeding, and abdominal pain. Laparotomy was done in view of an ultrasound which was suggestive of a well‑defined complex thick‑walled lesion of size 3.2 × 3.3 with a gestational sac and no cardiac activity in the right fallopian tube/adnexa suggesting tubal ectopic pregnancy. Beta‑human chorionic gonadotropin (β‑hCG) levels were done and noted to be as high as 9998 mIU/mL. Intraoperatively, a cornual ectopic pregnancy was found with no hemoperitoneum which was excised. Histopathology showed chorionic villi with variable size and hydropic change, myxoid stromal changes, and cistern formation with polar trophoblastic proliferation, based on which a diagnosis of molar pregnancy was made. Although ultrasonography and higher than usual serum β‑hCG levels are diagnostic of uterine molar pregnancy, they do not yield a proper diagnosis in ectopic molar pregnancy, hence, making it difficult to distinguish between an early ectopic molar pregnancy from a nontrophoblastic tubal pregnancy. The final diagnosis is usually made only after histopathology. A high degree of clinical suspicion of cornual pregnancy followed by histopathological examination of the products of conception is the standard for arriving at an appropriate diagnosis. Serial serum β‑hCG level follow‑up is recommended to rule out its malignant potential.
Pregnancy, Cornual ; Pregnancy, Ectopic ; Hydatidiform Mole

Sad fetus syndrome is a rare gestational trophoblastic disease wherein a hydatidiform mole coexists with a live fetus. We report a case of a 40‑year‑old G4P2 (2012) with 29 weeks gestational age who came in with vaginal bleeding and labor pains. A previous ultrasound done at 16 weeks of gestation showed a live fetus, a normal placenta, and a focal multicystic uterine mass. The beta‑human chorionic gonadotropin level was 1,500,000 mIU/mL. She delivered a live preterm female fetus weighing 900 g by partial breech extraction. The placenta was grossly normal. Postpartum hemorrhage secondary to uterine atony was encountered and a total hysterectomy with bilateral salpingectomy was performed. Cut section of the specimen revealed molar tissue at the anterofundal area with evidence of gross myometrial invasion. The histopathologic finding was consistent with a diagnosis of partial hydatidiform mole. This paper describes the incidence, pathology, clinical presentation, diagnosis, treatment, and postpartum course of this rare condition.
Hydatidiform Mole

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

Objective: This study aimed to determine if the beta-human chorionic gonadotropin (hCG) levels during the first 5 weeks after a molar evacuation predict progression to gestational trophoblastic neoplasia (GTN). Materials and Methods: This was a retrospective cohort study of complete mole cases managed at a Philippine tertiary hospital from January 2009 to December 2018. Extracted data were analyzed using applicable statistical tools. The level of significance was set at a P < 0.05 using two-tailed comparisons. Results: One hundred and fifty-five complete patient records were available for review. Disease progression in 15.48% of cases while regression in 84.52% were noted. Uterine size was larger in those who eventually had postmolar GTN (t: −3.12, df: 32.64, P: 0.01). Analysis of the receiver operating characteristic curve showed that optimum cut-off levels for predicting GTN at 1, 3, and 5 weeks after evacuation were 4,152 mIU/ml (sensitivity: 50%, specificity: 94.7%, area under the curve [AUC]: 0.75), 804 mIU/ml (sensitivity: 62.5, specificity: 96.9%, AUC: 0.94), and 541 mIU/ml (70.8%, specificity: 97.7%, AUC: 0.96), respectively. Conclusion The level of hCG within the first 5 weeks after molar pregnancy evacuation is predictive of progression to GTN.
Gestational Trophoblastic Disease ; Hydatidiform Mole

Background: The clinical presentation of patients with hydatidiform mole have changed in recent years due to earlier diagnosis as a result of widespread use of ultrasonography and availability of assays for human chorionic gonadotrophin. Objective: To determine the clinicopathologic profile of patients diagnosed with hydatidiform mole at the Philippine General Hospital from January 2013 to August 2018. Methods: This retrospective cross-sectional study included all patients with histologically confirmed diagnosis of hydatidiform mole managed at the Philippine General Hospital from January 2013 to August 2018. Medical records of patients were retrieved. All abstracted variables were analyzed retrospectively. The level of significance for all sets of analysis was set at p-value < 0.05 using two-tailed comparisons. Results: From January 2013 to August 2018, a total of 435 patients diagnosed with hydatidiform mole were managed at the Philippine General Hospital with a prevalence rate of 15.7/1,000 pregnancies. Diagnosis was made in the first trimester in 52% of patients. A quarter of the patients had pre-evacuation B-hCG levels of more than 1 million mIU/mL. Vaginal bleeding was the most frequent presenting symptom but only 59% of the patients had anemia requiring blood transfusion. Majority (90.57%) had a histopathologic diagnosis of complete hydatidiform mole. Conclusion The prevalence and clinicopathologic profile of patients with hydatidiform mole in the Philippine General Hospital have remained largely unchanged.
hydatidiform mole ; Pregnancy ; Female ; gestational trophoblastic diseases

Background: Administration of chemotherapy to prevent postmolar gestational trophoblastic neoplasia was first implemented in the 1960’s. However, its use has remained controversial. Objectives: This study aimed to describe the effect of chemoprophylaxis in preventing progression of hydatidiform mole to gestational trophoblastic neoplasia among patients managed in a tertiary hospital in Davao City from 2011 to 2015. Materials & Method: This retrospective cross-sectional study evaluated 123 cases of hydatidiform mole who were managed at a tertiary hospital in Davao City from the years 2011 to 2015. The patients’ charts were retrieved to get the clinicodemographic profile, progression to gestational trophoblastic neoplasia, and occurrence of adverse effects secondary to chemoprophylaxis. Patients with rising or plateauing beta human chorionic gonadotropin titer were identified within the 3-year period from molar evacuation. Collected data were analyzed using frequency and percentage distribution. Results: The mean age of the patients was 30.5 years, 24% of whom were noted in women more than 40 years of age. The average age of gestation on admission was 14.89 weeks. All patients had a histopathologic diagnosis of complete mole and at least one risk factor for developing postmolar gestational trophoblastic neoplasia. Patients did not experience any significant side effect to chemoprophylaxis. None of the patients developed gestational trophoblastic neoplasia within the 3-year period of monitoring. Conclusion The administration of chemoprophylaxis to patients diagnosed with hydatidiform mole may be effective against the development of postmolar gestational trophoblastic neoplasia.
Pregnancy ; Female ; Gestational Trophoblastic Disease ; Hydatidiform Mole ; Neoplasms ; Chemoprevention