Human Chorionic Gonadotropin Levels Research Articles

Outcomes of patients registered with the Queensland Trophoblast Centre diagnosed with gestational trophoblastic neoplasia who develop resistance to chemotherapy.

To audit outcomes of patients registered in the Queensland Trophoblast Centre (QTC) database who develop resistance to primary chemotherapy. To determine any risk factors that may predict first-line chemotherapy resistance in patients diagnosed with gestational trophoblastic neoplasia (GTN). Patients within the QTC who were diagnosed with GTN between January 2012 and December 2020 were reviewed. Of 138 patients with GTN registered in the QTC, 22 (15.9%) patients developed resistance to first-line chemotherapy. Three had high-risk GTN and 19 had low-risk GTN. Of the three high-risk patients, one patient died. This patient had an epithelioid trophoblastic tumour (ETT). The remaining two high-risk patients had complete hydatidiform moles (CHM) with GTN. Both achieved complete remission with salvage therapy. Of the 19 low-risk patients, one patient had a partial hydatidiform mole (PHM). This patient achieved remission following third-line treatment. The other 18 low-risk patients had CHM with GTN. All but two of these 18 patients were successfully treated with second-line chemotherapy, with the remaining two patients achieving remission with third-line chemotherapy. Five of the 18 patients received either actinomycin-D or methotrexate as salvage therapy. Thirteen patients were given multi-agent chemotherapy for second-line treatment. One patient in this group died but this was not due to her disease. Initial β human chorionic gonadotropin levels were not predictive of number of chemotherapy cycles or number of lines of chemotherapy required to achieve remission. GTN is a curable condition. If resistance to first-line chemotherapy occurred, most patients achieved remission with salvage therapy.

Maternal Serum Beta Human Chorionic Gonadotropin Level Estimation in Early Second Trimester as a Predictor for Pregnancy-induced Hypertension

Maternal Serum Beta Human Chorionic Gonadotropin Level Estimation in Early Second Trimester as a Predictor for Pregnancy-induced Hypertension

Epithelioid trophoblastic tumor in male patients with germ cell tumor: A clinicopathologic analysis of five cases

Epithelioid trophoblastic tumor (ETT) is an extremely rare chorionic-type neoplasm in the testis, with only seven cases reported in the literature. Here, we report five cases of testicular ETT from a single institution, constituting the largest series of this rare tumor to date. The patients had a mean age of 44 years (range, 20–68 years). Four patients had a previous history of testicular germ cell tumor (GCT) treated with chemotherapy, and they developed ETT in metastatic sites in a mean of 11 years (range, 3–15 years) after the initial diagnosis of testicular GCT. Only one patient had ETT in the testis. Three patients had a normal serum beta–human chorionic gonadotropin (β-hCG) level, and two patients had a level that was slightly elevated, but far below that typically seen in patients with choriocarcinoma. ETT was characterized by a proliferation of intermediate trophoblastic cells with abundant eosinophilic cytoplasm, and the tumors frequently had coagulative necrosis with eosinophilic debris, mimicking keratinizing squamous cell carcinoma. The trophoblastic phenotype of ETT was supported by its immunoreactivity for trophoblastic markers, including GATA-3 (3 of 3 cases tested), α-inhibin (3/4), p63 (3/5), and β-hCG (3/4). ETT was also positive for cytokeratin (4/4) and GCT marker SALL4 (3/3). Despite surgery and chemotherapy, two patients died of disease 17 months after ETT diagnosis, and three patients were alive with metastatic disease at a mean of 20 months (range, 15–28 months). Our results demonstrate that ETT may be an aggressive disease associated with distinct pathologic features and poor clinical outcome.

A case report on renal metastasis as an unusual presentation of choriocarcinoma

BackgroundChoriocarcinoma is an aggressively invasive neoplasm, characterized by its rapid proliferation and propensity for metastasis to distant organs via hematogenous dissemination. Lungs (80%), vagina (30%), pelvis (20%), liver (10%), and brain (10%) are the most frequently metastasized organs. Renal metastases are very rare. The clinical manifestations of choriocarcinoma varies depending on the site of disease, making diagnosis challenging. In this report, we provide a clinical case of choriocarcinoma with metastases to the renal and pulmonary systems, displaying symptoms akin to those observed in ectopic pregnancy.Case presentationA 27-year-old female, G2P1, with a previous history of full-term pregnancy in 2018, presented to the hospital with the onset of vaginal bleeding and accompanying abdominal aches. Investigations uncovered a left adnexal mass with a human chorionic gonadotropin (hCG) level of 77,4 mIU/mL and a left pulmonary nodule measuring 31 mm x 21 mm. Laparoscopy was performed due to the high suspicion of an ectopic pregnancy. However, no visible villi were identified during the surgery, and postoperative blood hCG levels continued to rise. A diagnostic curettage also failed to reveal any villi, maintaining the suspicion of a persistent ectopic pregnancy. Following two ineffective courses of methotrexate therapy, the patient was referred to our facility. Prior to her referral, an ultrasound had indicated a mass in the right kidney. However, upon arrival at our hospital, subsequent ultrasonography failed to detect any renal masses. Despite two months of outpatient monitoring, there was a sudden and significant increase in her serum hCG levels. An emergency laparoscopy was performed, revealing no pregnancy-related lesion. After surgery, the patient’s hCG levels dropped dramatically to less than one-tenth of the original amount. Multisite enhanced computed tomography(CT)revealed suspicious lesions in both the renal and pulmonary regions. Upon thorough multidisciplinary consultation, a diagnosis of choriocarcinoma was entertained. Consequently, the patient successfully underwent eight cycles of chemotherapy and has remained recurrence-free for the past year.ConclusionsThis case underscores the potential for choriocarcinoma in women of reproductive age who exhibit radiological signs of renal masses. Early and accurate diagnosis, followed by prompt intervention, is essential to prevent needless surgery procedures.

A-337 The Utility of Urinary Human Chorionic Gonadotropin Testing in the Emergency Department

Abstract Background Human chorionic gonadotropin (hCG) levels are measured in both urine and blood as an indication of suspected pregnancy, and assessment of progress of conception. It is also measured in the investigation of patients presenting with acute abdomen and suspected of ectopic or molar pregnancy. This study reviewed the utility of urine pregnancy test in a large university teaching hospital. Methods Results of all urinary hCG tests (using hCG Combo Pregnancy kit, MEDLINE, IL) performed as point of care in the emergency department during the year 2023 were obtained. Corresponding plasma hcG levels performed (Total β-HCG Alinity immunoassay, Abbott Diagnostics, IL) were also obtained. Analysis of hCG testing outcomes were assessed. Results A total of 2848 urinary hCG tests were performed during the study period. The majority 2113 (74.2%) of samples were negative for hCG whereas 835 samples (29.3) were positive. Among the positive hCG urine samples, 401 patients (48%) had plasma hCG requested and performed. Plasma hCG values ranged from < 2.4 (26.5) to 219,462.5 mIU/mL (median 16,872.35 mIU/mL). One plasma sample with corresponding positive urinary hCG result had plasma hCG level <2.4 mIU/mL which is below the detection limit of the assay suggesting a false positive urinary hCG result. Among the 13 patients with serial plasma hCG values, only one patient exhibited doubling (48 hours) hCG values when less than 13,000 mIU/mL. One patient had a declining serial hCG plasma values suggesting failing conception. The remaining patients with consecutive plasma hCG values cannot be assessed as either the time gap was excessive or hCG values were markedly elevated (> 30,000 mIU/mL). Conclusions Although the utility of urinary hCG testing in the emergency department appeared appropriate, unnecessary repeat analysis with appropriate plasma request represented 3.2%. An electronic test request duplicate notification may help resolve this unnecessary repeat.

8645 An Exploratory Analysis to Understand the Race Difference in Serum Levels of Human Chorionic Gonadotropin in Early Pregnancy

8645 An Exploratory Analysis to Understand the Race Difference in Serum Levels of Human Chorionic Gonadotropin in Early Pregnancy

Fertility-sparing surgical interventions for low-risk, non-metastatic gestational trophoblastic neoplasia.

The primary treatment approach for addressing low-risk nonmetastatic gestational trophoblastic neoplasia (LR-NMGTN) in women desiring fertility preservation involves chemotherapy. An alternative option for treatment is fertility-sparing surgical interventions, either alone or in combination with adjuvant chemotherapy. The hypothesised advantages of choosing fertility-sparing surgery in cases of LR-NMGTN include potential avoidance of adverse effects associated with chemotherapy, potential reduction in the number of chemotherapy cycles required to achieve complete remission, and potential reduction in time to remission. To measure the benefits and harms of fertility-sparing surgical interventions, with or without adjuvant chemotherapy, compared to primary chemotherapy alone, for the treatment of women with low-risk, non-metastatic gestational trophoblastic neoplasia (LR-NMGTN). We searched CENTRAL, MEDLINE, Embase, Web of Science, ClinicalTrials.gov and WHO ICTRP on 31 January 2024. We also searched abstracts of scientific meetings and reference lists of included studies. We included all randomised controlled trials (RCTs) comparing fertility-sparing surgical interventions, with or without subsequent adjuvant chemotherapy, versus primary chemotherapy as standard care for the treatment of women with LR-NMGTN. We employed standard Cochrane methodological procedures. We used the GRADE approach to assess the certainty of evidence for each outcome, if available. We focused on the following outcomes: treatment success rate, relapse, disease-specific mortality, death due to treatment, pregnancy rate, quality of life, and any adverse events. We included two RCTs, with a total of 151 participants contributing data to our analyses. Both studies used uterine curettage as the fertility-sparing surgical intervention. Fertility-sparing surgical intervention without subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 62 participants with varying hCG (human chorionic gonadotrophin) levels evaluated this comparison. Most of our outcomes of interest were not measured in this study. The relative risk of experiencing any adverse event could not be estimated as chemotherapy adverse effects were not reported. The study reported that there were no surgical complications. Chemotherapy was administered to 50% of participants in the intervention group after curettage because their hCG levels increased. Fertility-sparing surgical intervention with subsequent adjuvant chemotherapy versus primary chemotherapy alone One RCT involving 89 participants with hCG levels < 5000 IU/L evaluated this comparison. We judged the risk of bias in the study to be high. The evidence was very uncertain about the effect of uterine curettage with subsequent adjuvant chemotherapy on treatment success rate (RR 1.03, 95% CI 0.86 to1.23; 86 participants), relapse (RR 0.5, 95% CI 0.05 to 5.31; 86 participants), pregnancy rate (RR 0.86, 95% CI 0.31 to 2.34; 86 participants), and rate of adverse events (RR 1.15, 95% CI 0.63 to 2.13; 86 participants), all very low certainty evidence. The relative risks of disease-specific mortality and death due to treatment could not be estimated as there were no deaths in either group. There were no results for quality of life as this outcome was not reported. Uterine curettage is the only fertility-sparing surgical intervention for LR-NMGTN that has been evaluated in a randomised controlled trial. The evidence is very uncertain about the benefits and harms of uterine curettage, with or without subsequent adjuvant chemotherapy, compared to primary chemotherapy alone. The two available studies are small with a high risk of bias, and future research may find substantially different results for all reported outcomes. Larger RCTs, with appropriate clinical outcome measures, would be required to determine the benefits or harms of fertility-sparing surgical interventions for this population.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Assessment of Vitamin D, Vitamin B12, and Folate Levels in Recently Identified Pregnant Females.

Background: Pregnancy is a critical period where optimal maternal and fetal health depends on adequate nutritional status. Deficiencies in essential vitamins, such as vitamin D, vitamin B12, and folate, can result in adverse health outcomes. Objective: This study aims to assess the serum levels of vitamin D, vitamin B12, and folate in early pregnancy. Methodology: This cross-sectional research was conducted at Kurdistan Private Hospital in Duhok, Kurdistan Region of Iraq, from September 2022 to October 2023. The study included 150 pregnant women, with ages ranging from 18 to 45 years. Serum levels of vitamin D, vitamin B12, and folate were measured using the Automatic Clinical Chemistry Analyzer COBAS e 411 (Roche Diagnostics, Basel, Switzerland). Results: The mean age of the participants was 29 years (standard deviation [SD] = 6.2 years), with ages ranging from 18 to 45 years. The average serum human chorionic gonadotropin (HCG) level was 4,292 mIU/mL (SD = 3,947 mIU/mL), with a range of 98 to 10,000 mIU/mL. The mean serum levels were 17.8 ng/mL (SD = 11.6) for vitamin D, 367 pg/mL (SD = 245) for vitamin B12, and 11.5 ng/mL (SD = 4.6) for folate. The prevalence of vitamin D deficiency was significant, with 92 participants (61.3%) having levels below 20 ng/mL, 39 participants (26%) having insufficient levels ranging from 20 to 29 ng/mL, and only 19 participants (12.7%) having sufficient levels between 30 and 100 ng/mL. No cases of vitamin D toxicity (>150 ng/mL) were observed. Regarding vitamin B12, 32 participants (21.3%) had deficient levels (<200 pg/mL), while 118 participants (78.7%) had normal levels. Folate analysis revealed that 3 participants (2%) had moderate deficiency (2-3 ng/mL), 14 participants (9.3%) had mild deficiency (3-6 ng/mL), and there were no cases of severe folate deficiency (<2 ng/mL). Pearson correlation analysis showed weak correlations between the study variables, with the strongest being a weak negative correlation between age and serum folate levels (-0.18). Conclusions: The study found a high prevalence of vitamin D deficiency among the pregnant women included in the study, while the levels of folate and vitamin B12 were comparable to worldwide estimates. These findings focus attention on the importance of monitoring and addressing nutritional deficiencies at the beginning and throughout pregnancy. They also underline the need for preventive health interventions to correct these deficiencies and achieve the best outcomes for both maternal and fetal health.

Analysis of Risk Factors Associated with Gestational Diabetes Mellitus: A Retrospective Case-Control Study.

Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM. A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed. The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥30 years old, body mass index (BMI) in early pregnancy≥24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥30 years old (≥30 vs <30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183-3.878, p=0.012), BMI≥24.0 kg/m2 (≥24.0 kg/m2 vs 18.5-23.9 kg/m2, OR: 1.887, 95% CI: 1.041-3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022-3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046-7.863, p=0.041) were associated with GDM. Age of pregnant woman ≥30 years old, BMI≥24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.

Association between serum hormone levels in early pregnancy and risk of hypertensive diseases of pregnancy in women undergoing assisted reproduction.

We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction. Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated. A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317pg/mL, P4: 64 vs 29ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients. P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR.

Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq

ObjectiveA complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq. MethodsWe included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells. ResultsThe gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice. ConclusionRNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.

Recryopreservation impairs blastocyst implantation potential via activated endoplasmic reticulum stress pathway and induced apoptosis.

Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.

Morphological Diversity of the Endometrium in Choriocarcinoma Specimens and its Role in Differential Diagnosis.

Introduction: The morphological characteristics of the endometrium in patients with choriocarcinoma have not been well described. We described the endometrial morphology patterns in 46 choriocarcinomas and analyzed their relationship with the clinicopathological characteristics of these patients. Methods: Forty-six patients diagnosed with choriocarcinoma that had sufficient endometrial tissues for histopathological diagnosis were selected. Diagnoses of choriocarcinoma and secretory status of endometrium were reviewed. LHCGR expression of endometrium was evaluated by immunostaining. Results: Endometrial morphology was classified as secretory or nonsecretory. The 15 secretory specimens included 2 highly secretory and 13 common secretory specimens. The 31 nonsecretory patterns included 1 hyperplasia without atypia, 7 disordered proliferations, 13 typical proliferations, and 10 resting endometria. Among these, 11 specimens with overall nonsecretory patterns showed focally weak secretory changes surrounding the choriocarcinoma lesion. Secretory patterns were observed in classic choriocarcinomas (8/17) and monomorphic choriocarcinomas (7/21) but not in scanty-trophoblast choriocarcinomas (0/8). Secretory changes appeared significantly less frequently in patients who received multi-agent chemotherapy (4/25) than in those who did not (7/14) or received single-agent chemotherapy (4/7) (P = 0.030). The differences in age, months since the last pregnancy, pregnancy type, recurrence, specimen type, gross diameter, human chorionic gonadotropin (hCG) levels, and expression of hCG receptors were not statistically significant. Conclusions: The endometrial morphologies in choriocarcinoma were diverse, including various proliferative and secretory changes, but rarely hypersecretory changes, compared to the prevailing hypersecretory endometrium in hydatidiform moles. The variety in endometrial morphology was the consequence of ovarian hormonal disturbances of the hypothalamic-pituitary-gonadal axis by hCG from choriocarcinoma. Therefore, the endometrium may serve as a clue for histopathological diagnosis of choriocarcinoma. Our study presents the largest cohort reported to date to describe the diverse spectrum of endometrial changes in choriocarcinoma patients.

Increased Human Chorionic Gonadotropin Level in a Nonsexually Active Young Female

BackgroundQuantitative and qualitative human chorionic gonadotropin (hCG) tests are obtained in the emergency department (ED) to determine if a female of child-bearing age is pregnant. A positive hCG result is commonly assumed to indicate an intrauterine or other form of pregnancy. However, elevated hCG levels can also result from various other conditions, such as ovarian tumors, pituitary tumors, and thyroid disorders. Intracranial germ cell tumors, rare central nervous system tumors capable of secreting hCG, primarily affect adolescent and young adult females. Case ReportA 16-year-old female student without significant past medical history presented to our ED with a complaint of intermittent bilateral frontal headache for two days. Last menstrual period started two days prior to presentation. The headache was associated with phonophobia, photophobia, nausea, and vomiting. Serum quantitative hCG was elevated. She denied history of sexual activity or sexual assault. Transabdominal ultrasound was negative for intrauterine pregnancy. Obstetrics and gynecology as well as pediatric oncology were consulted. Subsequent investigations, including brain imaging, revealed a 3.5 cm mass in the right caudate nucleus and corpus callosum. The patient was diagnosed with an intracranial nongerminomatous germ cell tumor, necessitating hospitalization and prompt initiation of chemotherapy. Why Should an Emergency Physician Be Aware of This?An elevated quantitative hCG is not always indicative of pregnancy, especially in a young patient without sexual history. In the case of a nonrevealing transabdominal ultrasound, obstetrics and gynecology should be consulted for discussion of further testing and imaging. Emergency physicians should include malignancy high on their differential since prompt initiation of chemotherapy, evaluation by surgical services, and family planning will be required.

Gestational Trophoblastic Disease: Complete versus Partial Hydatidiform Moles.

Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty oocyte (complete hydatidiform mole (CHM); mostly 46,XX) or two sperms fertilize one oocyte (partial hydatidiform mole (PHM); mostly 69,XXY). Notably, recurrent occurrences are associated with abnormal genomic imprinting of maternal effect genes such as NLRP7 (chromosome 19q13.4) and KHDC3L (chromosome 6q1). Ongoing efforts to enhance identification methods have led to the identification of growth-specific markers, including p57 (cyclin-dependent kinase inhibitor 1C; CDKN1C), which shows intact nuclear expression in the villous cytotrophoblast and villous stromal cells in PHMs and loss of expression in CHMs. Treatment of hydatidiform moles includes dilation and curettage for uterine evacuation of the molar pregnancy followed by surveillance of human chorionic gonadotropin (HCG) levels to confirm disease resolution and rule out the development of any gestational trophoblastic neoplasia. In this review, we provide a synopsis of the existing literature on hydatidiform moles, their diagnosis, histopathologic features, and management.

A 20 year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital – a retrospective review

BackgroundNon-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital.MethodsThis is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis.ResultsWithin the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy.ConclusionsIntralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.

A Case of Partial Molar Pregnancy Complicated by HELLP and PRES

Introduction: The term gestational trophoblastic disease encompasses premalignant and malignant conditions arising from trophoblastic cells. Premalignant disorders include complete or partial hydatidiform mole, whereas malignant disorders include invasive mole, choriocarcinoma, and placental-site trophoblastic tumor. Partial hydatidiform moles are triploid in nature and occur when 2 sperm fertilize a single ovum. Preeclampsia is a syndrome complicating 2-8% of pregnancies which presents as new-onset hypertension plus proteinuria. The occurrence of hemolysis, elevated liver enzymes and low platelet count, referred to as HELLP syndrome, is a severe form of preeclampsia. A related severe manifestation is posterior reversible encephalopathy syndrome (PRES) - a clinicoradiological syndrome characterized by symptoms including headache, seizures, altered consciousness and visual disturbances. PRES is commonly associated with acute hypertension. The symptoms of PRES vary widely: i.e., the visual disturbance can vary from blurred vision and homonymous hemianopsia to cortical blindness. Seizures and status epilepticus are common. Although preeclampsia and HELLP syndrome rarely occur before 20-weeks of gestation, reports have suggested early occurrences of these hypertensive disorders specifically in the setting of a molar pregnancy. Case Report: The patient is a 23-year-old, female gravida 1 at 16 week 5 days who presented to an outside emergency department with a 3-day history of progressive abdominal pain which radiated to her back, arms, and shoulders. At the outside facility, the patient had multiple systolic blood pressures greater than 160 mmHg and had a witnessed 30-second seizure which resolved with an intravenous (IV) injection of 2-mg of Lorazepam and 4-gram magnesium sulfate loading dose. She was initiated on magnesium sulfate maintenance pending transfer to our institution. On admission, the patient met criteria for eclampsia and HELLP (platelets 79,000 K/uL, AST 144 U/L, ALT 96 U/L, LDH 482 U/L, Hemoglobin 8.7 g/dL). The beta human chorionic gonadotropin level (HCG) was greater than 200,000 mIU/mL. Bedside ultrasound suggested the presence of an enlarged cystic placenta and a growth restricted fetus (estimated fetal weight 124g, 2%). The patient and her family were counseled and the decision was made to proceed with misoprostol induction and termination of the pregnancy due to maternal indications. During the induction, the patient developed significant vaginal bleeding and was taken to the operating room for an uncomplicated dilation and evacuation. After the procedure, the patient developed progressive visual blurring with 4+ hyperreflexia. Magnetic resonance imaging (MRI) of the brain with and without contrast was obtained with findings significant for PRES. The MRI revealed T2 high-signal lesions within the cortex of the bilateral occipital lobes. Neurology was consulted and recommended blood pressure control and initiation of levetiracetam for seizure prophylaxis. She was initiated on long-acting nifedipine with subsequent blood pressure control. Patient’s visual symptoms and hyperreflexia resolved. Her liver function tests, platelets, and LDH also returned to normal. The patient received contraceptive counseling to prevent pregnancy during gestational neoplastic disease surveillance period. She underwent weekly beta-hCG until negative, followed by three weekly consecutive negative levels before spacing measurements to every 3 months for a period of six months per National Comprehensive Cancer Network (NCCN) guidelines. The pathology results indicated the presence of chorionic villi composed of both large hydropic and smaller normal-appearing villi, a 69.3-gram female fetus compatible with caudal neurocutaneous defect with abnormal localization of brain tissue. The genetic profile of the villous tissue consisted of two sets of dispermic paternal alleles in addition to one set of maternal alleles consistent with a partial mole diagnosis. Discussion: There is an association between preeclampsia and molar pregnancy. Of partial hydatidiform molar pregnancies, 41.9% will develop the symptoms of preeclampsia if left untreated. Although the pathophysiology of eclampsia spectrum disorders is incompletely understood, some evidence points to the role of increased death of trophoblasts and the maternal inflammatory response to trophoblast deportation. Additional evidence points to angiogenic factor imbalance and interestingly, molar placentas produce high levels of antiangiogenic factors. Other causative agents include placental factors that trigger maternal endothelial activation. It is known that trophoblastic debris shed from the placenta into the maternal blood is associated with this condition. It has been demonstrated that trophoblastic debris from molar pregnancies also induces endothelial cell activation through heat-shock protein 70 (HSP70) expressed on a hydatidiform molar placenta, which may be a pathogenic signal to endothelial cells. This case reiterates the association between hydatidiform moles and the hypertensive disorders of pregnancy possibly supporting the theories that such disorders may share an etiologic linkage through trophoblast debris and angiogenic factor imbalance. This case also supports screening molar pregnancies for severe preeclampsia syndrome.

GCT-17. EXPLORING NEW THRESHOLDS FOR BETA-HCG IN CENTRAL NERVOUS SYSTEM GERMINOMA

Abstract BACKGROUND Human chorionic gonadotropin (beta-HCG) levels in serum and cerebrospinal fluid (CSF) are critical in the management of patients with germinoma. The threshold for beta-HCG diagnosis is a topic of debate and differs in Europe, ≤50 IU/L, North America ≤100 IU/L, and ≤200 IU/L in Brazil/Japan. METHODS We conducted a meta-analysis of English-language publications (1990-2023) to assess how beta-HCG cut-off levels impact treatment outcomes. Standard descriptive statistics summarized all data. RESULTS Forty-nine patients with biopsied germinoma were identified. Eighteen had beta-HCG level of 50-100 IU/L (cohort 1), 21 had 100-200 IU/L (cohort 2), and 10 had &amp;gt;200 IU/L (cohort 3). In cohort 1, treatment with chemotherapy plus radiotherapy was administered to 9 patients. Eight of them received radiotherapy like germinoma treatment (≤30Gy), primarily employing whole ventricle irradiation (WVI). Nine patients received radiotherapy alone with total dose 30-59.6Gy. Fifteen patients in cohort 2 received chemotherapy plus radiotherapy. Eight of them received radiotherapy ≤30Gy for different fields [WVI – 4, whole brain (WB) – 3, cerebrospinal irradiation (CSI) – 1). In 7 patients the dose of radiotherapy exceeded 30Gy (local radiotherapy – 4, CSI – 3). Radiotherapy alone was used in 5 patients, chemotherapy alone – 1 patient. In cohort 3, radiotherapy only was primarily used. Six patients received CSI (50-54Gy), one – CSI+WB+local radiotherapy (12.8Gy+27.2Gy+50.6Gy). One patient received combined treatment and 2 patients received chemotherapy alone. Relapses occurred in each cohort. In cohort 1 – 2 metastatic relapses (1 after WVI 24Gy, 1 after radiotherapy &amp;gt;30Gy). Three children from cohort 2, who received chemotherapy plus radiotherapy were diagnosed with relapse (1 after WB 23.4Gy, 2 after radiotherapy &amp;gt;30Gy). In cohort 3 two metastatic relapses were diagnosed – only after chemotherapy. CONCLUSIONS Relapse rates across all beta-HCG level are similar. However, study groups are small and treatment regimens vary, warranting further investigation.

Single day 14 serum hCG values allow prediction of viable pregnancy and are significantly higher in frozen as compared to fresh single blastocyst transfer

PurposeTo evaluate if single serum human chorionic gonadotropin (hCG) level measurements are sufficient for pregnancy monitoring after single embryo transfer (sET) and to compare the hCG levels between fresh (FRET) and frozen embryo transfers (FET) in medically assisted reproduction.MethodsThis was a retrospective exploratory cohort study including all patients who met the inclusion criteria, who received a single FRET (n = 249) or FET (n = 410) of a day five blastocyst at the IVF clinic at the Johannes Kepler University Linz between 2011 and 2020. hCG levels were measured on day 14 after embryo transfer. Threshold values for the viability of pregnancies were determined using receiver operating characteristic (ROC) curves.ResultsSignificantly higher hCG levels were found in those who received FET than in those who received FRET (1222.8 ± 946.7 mU/ml vs. 862.7 ± 572.9 mU/ml; p < 0.001). Optimal threshold values predicting a viable pregnancy were 368.5 mU/ml and 523 mU/ml in the FRET and FET groups, respectively.ConclusionsAfter FET, higher hCG values after 14 days of embryo transfer must be considered in pregnancy monitoring. Additionally, a single threshold hCG value seems to be sufficient for determining pregnancy viability. To exclude ectopic pregnancies, subsequent ultrasound examination is a mandatory requirement.