Measurement Of Human Chorionic Gonadotropin Research Articles

Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices.

Quantitative human chorionic gonadotropin (hCG) measurements are used to manage women classified with a pregnancy of unknown location (PUL). Two point of care testing (POCT) devices that quantify hCG are commercially available. We verified the i-STAT 1 (Abbott) and the AQT 90 FLEX (Radiometer) prior to use in PUL triage. Tests for precision, external quality assurance (EQA), correlation, hook effect and recovery were undertaken alongside a POCT usability assessment during this prospective multi-center verification. Coefficients of variation ranged between 4.0 and 5.1 % for the three i-STAT 1 internal quality control (IQC) solutions and between 6.8 and 7.3 % for the two AQT IQC solutions. Symmetric differences in POCT EQA results when compared with laboratory and EQA stock values ranged between 3.2 and 24.5 % for the i-STAT 1 and between 3.3 and 36.9 % for the AQT. Correlation coefficients (i-STAT 1: 0.96, AQT: 0.99) and goodness of fit curves (i-STAT 1: 0.92, AQT: 0.99) were excellent when using suitable whole blood samples. An hCG hook effect was noted with the i-STAT 1 between 572,194 and 799,089 IU/L, lower than the hook effect noted with the AQT, which was between 799,089 and 1,619,309 IU/L. When hematocrit concentration was considered in sample types validated for use with each device, hCG recovery was 108 % with the i-STAT 1 and 98 % with the AQT. The i-STAT 1 scored lower on usability overall (90/130) than the AQT (121/130, p<0.001, Mann-Whitney). Both hCG POCT devices were verified for use in clinical practice. Practical factors must also be considered when choosing which device to use in each unit.

Evaluation of a New Model for Human Chorionic Gonadotropin Rise in Pregnancies of Unknown Viability

Abstract For early pregnancy management, quantitative serum human chorionic gonadotropin (hCG) measurements and transvaginal ultrasonography are the standard clinical guides. Current guidelines use the change in hCG levels to determine likely location of the pregnancy but represent a minimal rate to predict viability. When incorrectly used, these are inaccurate. This study examined the performance of a new hCG threshold model and compared it with 3 established models. The study is a retrospective cohort study. All individuals with at least 2 consecutive quantitative hCG serum levels seen at the University of Missouri–Columbia from January 1, 2015, until March 1, 2020, were screened for study eligibility. Eligibility requirements were 3-fold: first, patients who presented with pregnancy of unknown viability; second, they had an initial hCG level between 2 and 5000 mIU/mL, maintaining the first interval of no greater than 7 days between testing; and third, the final pregnancy outcome was confirmed. Exclusion occurred for patients who had germ cell tumors, had molar pregnancies, had an intrauterine device in place, utilized hCG monitoring for a molar pregnancy or elective abortion, utilized assisted reproductive technology to achieve pregnancy, or were lost to follow-up. Results of the study came from a pool of 688 patients who met all the inclusion criteria. They contributed an average of 2.3 measurements per patient for a total of 1554 hCG measurements. There was an average of 10.1 days for follow-up. Of those patients included, 167 had viable intrauterine pregnancy (IUP) (24.3%), 463 experienced early pregnancy loss (67.3%), and 58 had ectopic pregnancies (8.4%). The rates of rise in values up to 4 days and again between 4 and 6 days were added for a total rate or rise. Because this was a retrospective study, a calculation was used when hCG levels were not available on day 4 or 6. The values were calculated to be conservative and to avoid incorrectly classifying any viable pregnancy as nonviable. Strengths of the study include its large sample size, its inclusion of all 3 pregnancy outcomes, verified pregnancy outcomes, and subsequent misclassification assessments based off of the aforementioned strength. This study confirmed 122 of 168 viable IUPs (72.6%) had live births, and the simple nature of the study allows for easy integration into clinical practice. Finally, the new model allows for greater variation in days on which a patient must present for care. Study limitations included imputed values from hCG samples not specifically collected on day 4 or 6. Despite this, application of the proposed model utilizing merely known values resulted in better performance. In addition, minimal rise for hCG rates in this data set may be a result of internal validation that may differ in larger, multi-institutional data sets. Furthermore, it must be remembered that current methods using hCG thresholds to determine pregnancy viability rely predominantly on mathematical data analysis and thereby do not reach 100% accuracy thresholds due to biologic variations. Based on this reason, hCG rises below cutoffs established should not mandate a reflexive nonviability diagnosis. The study concluded that although shared decision-making remains paramount in determining management steps, the proposed new model simultaneously reduced unnecessary interventions and optimized correct classification rates for all subgroups of pregnancy. Further prospective studies and investigations of cost-effectiveness are needed before widespread model implementation for pregnancy classification.

Assessment of kisspeptin and trappin level in Iraqi women with early pregnancy loss: a cross sectional study

Background: Early pregnancy loss (EPL) is a prevalent medical condition that can have significant and long-lasting impacts on an individual's life. At present, the determination of the feasibility of initial gestation is ascertained through the measurement of serum human chorionic gonadotropin (hCG) concentrations. Notwithstanding, an elevated hCG level in women during their initial trimester who exhibit bleeding does not constantly imply a sustainable pregnancy. Kisspeptin, a well-established regulator of maturation that is widely present in the placenta, represents a valuable biomarker for the assessment of miscarriages and placental dysfunction. The objective of this investigation was to ascertain key biomarkers (namely kisspeptin, trappin, and hCG) in females who have experienced a previous miscarriage. Methods: The study included 90 participants, including 60 pregnant women having a history of abortion in the first trimester and 30 healthy individuals who attended Al Kadhimiya Teaching Hospital and Abu Ghraib Hospital Baghdad Governorate, and ranged in age from 18 to 38 years. Sera from all participants were tested to evaluate various research parameters. Results: Trappin levels were less crucial to hCG than kisspeptin levels. The risk of miscarriage decreases as kisspeptin levels increase. Conclusions: The development of a preliminary screening test aimed at identifying patients who are at risk of miscarriage could potentially offer benefits in terms of offering supplementary emotional assistance and continuation of medical care. Kisspeptin has been identified as a prospective indicator for placental performance. Kisspeptin exhibits potential as a biomarker for assessing the viability of pregnancy and holds promise for clinical utility in the development of a precise diagnostic tool for early pregnancy outcome prediction.

Medication Abortion and Uterine Aspiration for Undesired Pregnancy of Unknown Location: A Retrospective Cohort Study

ABSTRACT Uncertain diagnosis can complicate the evaluation and treatment of patients presenting for undesired pregnancy termination at early gestational ages. Pregnant patients with no ultrasonography-identifiable pregnancy location receive classification of pregnancy of unknown location (PUL). Until receiving a definitive intrauterine pregnancy (IUP), ectopic pregnancy, or early pregnancy loss diagnosis, these patients are often managed expectantly with serial serum human chorionic gonadotropin (hCG) measurements and ultrasonography. Immediate treatment of undesired PUL with low-risk for ectopic pregnancy can be performed in ways that minimize the risk. This retrospective cohort study reviewed outcomes of pregnancies for PUL-diagnosed patients presenting at Planned Parenthood in Minnesota, North Dakota, and South Dakota to receive induced abortions between July 1, 2016, and December 31, 2019. Care of patients with PUL included assessment of health history, counseling, and ectopic pregnancy precaution reviews. Clinicians then proceeded to triage patients into low- and high-risk groups based on transvaginal ultrasonography findings and patient symptoms. For PUL patients deemed low risk for ectopic pregnancy, the choices of expectant management or induced abortion were given. Patients proceeding with induced abortions then proceeded with uterine aspiration or medication abortion. The primary objective compared the diagnosis of pregnancy location to time for 3 groups, which included the groups of patients choosing immediate treatment (via uterine aspiration or medical management), and the group of patients who initially chose expectant management (delay for diagnosis). Time to diagnosis, as measured in days, was recorded from initial PUL diagnosis until final pregnancy location diagnosis. A spontaneous decline of serum hCG after 48–72 hours in the delay-for-diagnosis group was recorded as a spontaneously resolved PUL consistent with spontaneous abortion. Incidence of ectopic pregnancies, complications such as transfusion-requiring hemorrhages, and failure to adhere with follow-up guidelines (greater than 60 days from PUL diagnosis without clinical contact and/or a pregnancy diagnosis) were also recorded. From a total of 19,151 abortion counters across the study period, 2.9% of patients (553) were diagnosed with PUL. High-risk diagnoses were given to 9.4% of patients (52), based on concerns from symptoms and ultrasounds (27 of these had ectopic pregnancies [51.9%]). Low-risk diagnoses were given to 90.6% of the remaining patients (501), who were given a choice of management. When compared with expectant management, results indicated that low-risk patients with undesired PUL experienced fewer days to diagnosis with immediate treatment by uterine aspiration (and a similar time frame to diagnosis with abortion via medication). For uterine aspiration, abortion treatment using simultaneous serial hCG trending was effective. Although this study lacked statistical power to detect differences between groups, there was an overall low complication rate (0.2%). Strengths of the study include the exclusive focus on true-PUL patients, as well as the large sample size. Generalizability was potentially increased by the fact that various physicians triaged PUL patients in the study setting without increases in complications. A weakness of the study was that even with a 60-day follow-up window, the 27% follow-up nonadherence rate was higher than the 16% of Goldberg et al. In addition, the retrospective nature of the study was also a weakness. Finally, given the inability to observe direct comparison for efficacy of delayed medication versus immediate abortion due to higher rates of spontaneous abortion in the delay-for-diagnosis group, the outcomes of the study are limited by small numbers. This study shows that proceeding with an induced abortion in patients with PUL and undesired pregnancy are effective and safe as long as a plan for close follow-up with hCG is in place.

Human Chorionic Gonadotropin-A Review of the Literature.

The measurement of human chorionic gonadotropin (hCG) levels in different body fluids is a commonly utilized tool in obstetrics and gynecology, as well as other fields. It is often one of the first steps in the medical workup of female patients, and the results and interpretation of this test can have significant downstream ramifications. It is essential to understand the uses and limitations of hCG as a testing and therapeutic measure to appropriately evaluate, counsel, and treat patients. The purpose of this article is to review the current literature on hCG, including its origins, structure, pharmacokinetics, metabolism, and utility in testing and medical treatment. Original research articles, review articles, and guidelines on hCG use were reviewed. While the primary function of hCG is to maintain early pregnancy, testing for hCG demonstrates that this molecule is implicated in a multitude of different processes where results of testing may lead to incorrect conclusions regarding pregnancy status. This could affect patients in a myriad of settings and have profound emotional and financial consequences. In addition, hCG testing may be revealing of alternative pathology, such as malignancy. It is imperative to understand the nuances of the physiology of hCG and testing methods to effectively use and interpret this test for appropriate patient management.

Impact of empathic physician contact on patient anxiety and distress during the waiting period after embryo transfer: a randomized controlled trial

Research questionCan an empathic physician phone call in the interval between embryo transfer and first serum human chorionic gonadotrophin measurement decrease anxiety and distress amongst patients undergoing IVF? DesignThis was a randomized controlled trial at a single academically-affiliated fertility centre including patients aged 18–43 undergoing their first embryo transfer with autologous fresh or euploid cryopreserved embryos following preimplantation genetic testing for aneuploidies (frozen embryo transfer, FET/PGT-A). After embryo transfer, participants were randomized to a 5-minute scripted phone call (intervention) from a single physician 3–4 days after embryo transfer or to routine care. The primary and secondary outcomes included were change in State-Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS) scores from the start of IVF stimulation to 8–9 days after embryo transfer, respectively. ResultsA total of 231 participants (164 fresh, 67 FET/PGT-A) were randomized to intervention (n = 116) or routine care (n = 115). While mean STAI and HADS scores increased in both groups, the intervention group experienced lower mean increases than the routine care group for both the STAI (3.3 [0.97] versus 7.8 [1.10], respectively; P = 0.002) and the HADS (0.3 [0.44] versus 2.4 [0.53], respectively; P = 0.003). Most participants in the intervention group found the call helpful (91.4%) and reported that it decreased distress and anxiety (81%). ConclusionsA brief empathic phone call from a physician during the waiting period resulted in significantly lower self-reported levels of patient anxiety and distress. As the intervention in this study averaged 5 min, implementing this in clinical practice would not be onerous and may ease the distress associated with the waiting period.

Early prediction of post-molar gestational trophoblastic neoplasia and resistance to methotrexate, based on a single serum human chorionic gonadotropin measurement

BackgroundClinicians are unable to provide individualized counseling regarding risk of progression for patients with a complete hydatidiform mole (CHM). We developed nomograms enabling early prediction of post-molar gestational trophoblastic neoplasia (GTN) and resistance to methotrexate (MTX) based on a single serum human chorion gonadotropin (hCG) measurement. MethodsWe generated two nomograms with logistic regression: to predict post-molar GTN, and MTX resistance. For patients with high probability to progress to post-molar GTN or MTX resistance, we determined hCG cut-offs at 97.5% specificity to select patients for additional- or adjustments in current treatment. ResultsThe nomograms had a good to excellent ability to distinguish either between patients with uneventful hCG regression versus progression to post molar GTN, or between patients cured by MTX versus patients in whom resistance would occur. At 97.5% specificity, we identified 66% (95%CI 56–75) of the 149 patients who would progress to post-molar GTN, four weeks after initial curettage. For patients treated with MTX, we identified 55% (95%CI 23–83) of the 43 patients who would become resistant, preceding their third course at 97.5% specificity. ConclusionThe nomograms and cut-off levels can be used to assist in counseling for patients diagnosed with CHM.

The current situation of health services for hydatidiform mole in Cambodia

Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n=29), provincial hospitals (n=42), district hospitals (n=20), health centers (n=6), and others (n=29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

Placental Villous Explant Culture 2.0: Flow Culture Allows Studies Closer to the In Vivo Situation.

During pregnancy, freely floating placental villi are adapted to fluid shear stress due to placental perfusion with maternal plasma and blood. In vitro culture of placental villous explants is widely performed under static conditions, hoping the conditions may represent the in utero environment. However, static placental villous explant culture dramatically differs from the in vivo situation. Thus, we established a flow culture system for placental villous explants and compared commonly used static cultured tissue to flow cultured tissue using transmission and scanning electron microscopy, immunohistochemistry, and lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG) measurements. The data revealed a better structural and biochemical integrity of flow cultured tissue compared to static cultured tissue. Thus, this new flow system can be used to simulate the blood flow from the mother to the placenta and back in the most native-like in vitro system so far and thus can enable novel study designs.

An enzyme immunoassay to determine human chorionic gonadotropin (HCG) in serum and urine samples using an ultra-microanalytical system

The determination of Human Chorionic Gonadotropin (HCG) in biological fluids is of great interest in the early pregnancy diagnostics, the evaluation of pregnancy disorders, as a tumor marker, as a screening procedure for anti-doping control, and many other purposes. A simple sandwich-type UltraMicro Enzyme-Linked ImmunoSorbent Assay (UMELISA) has been developed for the measurement of HCG in serum and urine samples. Strips coated with a high affinity MAb directed against HCG are used as solid phase, to ensure the specificity of the assay. The HCG assay was completed in 1.5 h, with a measuring range of 0.76–400 mIU/mL. The intra- and inter-assay coefficients of variation were lower than 10 %, depending on the HCG concentrations evaluated. Recovery percentages were 96.43–97.16 % (serum) and 98.10–99.04 % (urine). The assay detected intact HCG, nicked HCG, HCG β, and nicked HCG β, and did not recognize any of the interfering molecules tested. Regression analysis showed a good correlation with Elecsys in serum (n = 1459, r = 0.952, ρc = 0.948) and urine (n = 869, r = 0.988, ρc = 0.978). A good correlation was also found with 84 RIQAS samples analyzed with the kits Elecsys (r = 0.969, ρc = 0.957), Architect (r = 0.982, ρc = 0.970), Dimension (r = 0.989, ρc = 0.977), and Bioscience (r = 0.992, ρc = 0.980), all with a p < 0.01. Comparison with transvaginal ultrasonography in early pregnancy detection showed a specificity and a sensitivity of 100 % (n = 2385, κ = 1). The analytical performance characteristics of UMELISA HCG endorse its use for the quantification of HCG in serum and urine samples. This assay will make a cost-effective diagnostic kit accessible to low-income countries and is now available in the Cuban Public Health System.

The Application of the EP9-A Protocol in the Analysis of the Performance of the Immunofluorescence Assay for HCG Detection.

ObjectiveThe present study aims to evaluate the comparability of the results of two methodologies for detecting human chorionic gonadotropin (HCG) to assess whether the immunofluorescence method for detecting HCG is adequate for clinical applications.MethodsReferring to the protocol requirements of the American Clinical Laboratory Standards Institute (CLSI) EP9-A2 (methodological matching and bias assessment with patient samples), we collected 40 fresh serum specimens from our outpatients and inpatients, including 20 specimens with abnormal HCG concentrations (eight samples with different concentration ranges were selected daily and HCG was measured simultaneously with the two testing systems for five consecutive days). The assays were performed on a Dxl 800 fully automated immunoassay analyzer from Beckman Coulter Inc., USA, as a comparative method and on a Jet-iStar 3000 immunoassay analyzer from Zhonghan Shengtai Inc. as an experimental method. Methodological comparison and bias assessment of the results of the two methods for HCG detection were performed. The OLR regression model was used for calculating bias and regression analysis, and Spearman’s rank correlation coefficient was used for correlation analysis. The correlation and comparability of the two systems were calculated based on the results of the analysis.ResultsA good correlation in HCG results in the range of 5–50,000 U/mL was obtained from the two assay systems (r = 0.998) with the regression equation of y = 1.020x + 12.96. The estimated deviation was within the permissible deviation and acceptable.ConclusionThe results of HCG measurement by the two different assay systems were well correlated and comparable.

Gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in a retrospective cohort of 7761 patients in France

The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring strategies for certain patients. This study aimed to determine the risk of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in women with molar pregnancy and identify risk factors for this type of malignant transformation to optimize follow-up protocols after human chorionic gonadotropin normalization. This was a retrospective observational national cohort study based at the French National Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020 for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned spontaneously to normal. Among 7761 patients whose human chorionic gonadotropin levels returned to normal, 20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar pregnancy. The median time to diagnosis of malignant transformation after human chorionic gonadotropin normalization was 11.4 months (range, 1-34 months). At diagnosis, 16 of 20 patients (80%) had the International Federation of Gynecology and Obstetrics stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients (45%), the most common first-line treatment was combination chemotherapy. A quarter of these tumors (5 of 20) were histologically proven placental site or epithelioid trophoblastic tumors. In univariate analysis, the factors significantly associated with a higher risk of developing gestational trophoblastic neoplasia after the end of the normal human chorionic gonadotropin monitoring period were age of ≥45 years (odds ratio, 8.3; 95% confidence interval, 2.0-32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio, 7.7; 95% confidence interval, 1.1-335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3-206; P<.001). In this group of patients with gestational trophoblastic disease, none of the those with pathologically verified partial mole had malignant transformation, supporting the current recommendation of stopping human chorionic gonadotropin monitoring after 3 successive negative tests. In cases of complete mole or twin molar pregnancy, weproposed to extend the monitoring period with quarterly human chorionic gonadotropin measurements for an additional 30 months in patients with the identified risk factors for late malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization, ≥8 weeks).

Early Serum hCG in IVF: Are We Trending in the Right Direction?

Human chorionic gonadotropin (hCG) measurements may be the earliest indicator of fertility cycle success, available several weeks before an ultrasound would be diagnostic for pregnancy. Outcomes of these cycles are high stakes for a couple, and the earliest reassurance of a normal pregnancy would be beneficial for their well-being. Additionally, earlier diagnosis can allow for more rapid management by providers in the case of abnormal pregnancies. Therefore, establishing normal values for initial hCG level and early hCG kinetics is of great interest. There are many factors involved in assisted reproductive techniques that may lead to alterations in hCG kinetics when compared with spontaneous pregnancies. We aim to characterize normal hCG values for in vitro fertilization (IVF) pregnancies and review how different aspects of the IVF process may alter these trends in order to establish how best to counsel patients during the waiting period.

Manejo Conservador de Retención de Productos de la Concepción con Anticonceptivos Orales Combinados. Presentación de Caso

RESUMEN Objetivo: presentar el caso de una paciente con retención de productos de la concepción (RPC) después de aborto médico, tratada con anticonceptivos orales combinados (ACOC), y efectuar revisión de la literatura. Caso Clínico: paciente de 37 años, con sangrado genital escaso y leve dolor pélvico, quien tuvo aborto provocado con misoprostol cuatro días antes, acude sin signos de infección, con endometrio mixto de 18,5 mm. Durante seis semanas de seguimiento persiste sangrado y endometrio mixto engrosado, con disminución lenta de la gonadotrofina corionica humana (GCH); se sospecha RPC, se suministra ciclo de ACOC y al terminarlos expulsa completamente el tejido retenido. Metodología: búsqueda bibliográfica en bases de datos Google Scholar, Science Direct, RIMA, PubMed. Revisión de literatura: la RPC se presenta después de parto o aborto (más frecuente). Criterios diagnósticos: sangrado persistente, hallazgos ecográficos y medición de GCH. Diagnóstico diferencial: enfermedad trofoblastica gestacional y malformaciones arteriovenosas uterinas. Es factible el manejo conservador, con bajas tasas de infección o procedimientos quirúrgicos. Ante la evolución prolongada, presencia de signos de infección o hemorragia importante, se impone la evacuación quirúrgica, tradicionalmente con dilatación y legrado, y más recientemente resección histeroscópica. La bibliografía reciente sugiere el uso de ACOC como manejo médico. En nuestro caso, la paciente tomó un ciclo de ACOC y al terminarlos presentó expulsión de los restos retenidos. Conclusiones: el manejo conservador de la RPC con ACOC surge como una opción en casos seleccionados; son necesarios estudios controlados para definir su utilidad.Palabras clave: misoprostol, aborto incompleto, anticonceptivos orales combinados.

The potential use of urinary hCG measurements in the management of pregnancies of unknown location

Multiple measurements of serum human chorionic gonadotropin (hCG) are used to predict the final pregnancy outcome for women with a pregnancy of unknown location (PUL) and monitor the management of ectopic pregnancy (EP). Urine-based testing would be more convenient and economical. This prospective cohort study involving 80 women assessed the degree of correlation between serum and urine hCG levels and whether urine hCG levels have the potential to impact clinical decision making in the management of women with a PUL. Paired urine and serum hCG measurements differed quite widely but were well correlated and the degree of correlation improved after creatinine correction. Although serial serum hCG measurements appear to be better for the overall prediction of pregnancy outcome in PUL (AUC 0.77–0.94 compared to corrected urine AUC 0.69–0.84), serial urine hCG measurements may have a role in identifying subtypes of low-risk PUL (AUC 0.83–0.84).

Increased Circulating Levels of Tissue-Type Plasminogen Activator Are Associated with the Risk of Spontaneous Abortion During the First Trimester of Pregnancy.

Spontaneous abortion is a common complication in early pregnancy, with an incidence of around 20%. Ultrasound scan and measurement of human chorionic gonadotropin are used to identify patients at risk of spontaneous abortion; however, there is a clinical need to find new biomarkers to prospectively identify patients before the onset of clinical symptoms. Here, we aim to investigate potential biomarkers of spontaneous abortion taken in the first clinical appointment of pregnancy. A case–control study was conducted based on a prospectively collected cohort in which cases and controls were retrospectively stratified based on pregnancy outcome: normal healthy pregnancies (controls = 33) and pregnancies that ended in spontaneous abortion (cases = 10). We evaluated extracellular vesicles isolated by precipitation with ExoQuick™ and protein concentrations of tissue plasminogen activator, leptin, and adiponectin measured by ELISA. The extracellular vesicles showed the typical morphology and membrane proteins: CD63, Alix, and Flotilin-1. The size distributions of the isolated extracellular vesicles were 112 ± 27 and 118 ± 28 nm in diameter for controls and spontaneous abortion, respectively, and the total amount of extracellular vesicles did not show any difference between controls and the spontaneous abortion group. The tissue plasminogen activator showed a significant difference (p = 0.0004) between both groups, although neither adiponectin nor leptin revealed significant changes, indicating that women who had spontaneous abortions have significantly higher levels of tissue plasminogen activator than women who had normal pregnancies.

A tutorial on dynamic risk prediction of a binary outcome based on a longitudinal biomarker.

Dynamic risk predictions based on all available information are useful in timely identification of high‐risk patients. However, in contrast with time to event outcomes, there is still a lack of studies that clearly demonstrate how to obtain and update predictions for a future binary outcome using a repeatedly measured biomarker. The aim of this study is to give an illustrative overview of four approaches to obtain such predictions: likelihood based two‐stage method (2SMLE), likelihood based joint model (JMMLE), Bayesian two‐stage method (2SB), and Bayesian joint model (JMB). We applied the approaches to provide weekly updated predictions of post–molar gestational trophoblastic neoplasia (GTN) based on age and repeated measurements of human chorionic gonadotropin (hCG). Discrimination and calibration measures were used to compare the accuracy of the weekly predictions. Internal validation of the models was conducted using bootstrapping. The four approaches resulted in the same predictive and discriminative performance in predicting GTN. A simulation study showed that the joint models outperform the two‐stage methods when we increase the within‐ and the between‐patients variability of the biomarker. The applicability of these models to produce dynamic predictions has been illustrated through a comprehensive explanation and accompanying syntax (R and SAS®).

State-of-the-Art Workup and Initial Management of Newly Diagnosed Molar Pregnancy and Postmolar Gestational Trophoblastic Neoplasia.

Gestational trophoblastic disease refers to a series of interrelated tumors arising from the placenta, including benign molar pregnancies as well as the malignant conditions termed gestational trophoblastic neoplasia (GTN). GTN most commonly follows a molar pregnancy but may develop after any gestation. The wide availability of first trimester ultrasound and serum human chorionic gonadotropin (hCG) measurement has changed the presentation of molar pregnancy in recent decades from a second trimester to a first trimester disease, such that most patients have few symptoms at diagnosis. With identification of molar pregnancy at earlier gestations, accurate diagnosis increasingly relies on expert histopathology coupled with ancillary molecular and genetic techniques. However, earlier diagnosis has not changed the risk of postmolar GTN. Although most molar pregnancies are treated with dilation and curettage, hysterectomy may be appropriate in select cases when future fertility is not desired. After treatment of molar pregnancy, close surveillance with serial hCG monitoring is essential to diagnose GTN and identify the need for chemotherapy. Physicians following hCG levels should understand the performance characteristics of the test, including common causes of false-positive and false-negative results. After a diagnosis of postmolar GTN is made, selection of single-agent or multiagent chemotherapy depends on accurate assignment of the clinical stage and risk stratification by the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system. Surgical treatment of postmolar low-risk GTN, including both second uterine curettage and hysterectomy, may decrease subsequent need for or duration of chemotherapy. Cure rates for postmolar low-risk GTN approach 100%, and subsequent pregnancy outcomes for patients reflect those of the general population.

Hyperglycosylated human chorionic gonadotropin as a predictor of ongoing pregnancy

Hyperglycosylated human chorionic gonadotropin, the predominant human chorionic gonadotropin variant secreted following implantation, is associated with trophoblast invasion. To determine whether the initial serum hyperglycosylated human chorionic gonadotropin differs between ongoing and failed pregnancies, and to compare it to total serum human chorionic gonadotropin as a predictor of ongoing pregnancy. Women undergoing fresh/frozen invitro fertilization cycles at a university-based infertility clinic with an autologous day 5 single embryo transfer resulting in serum human chorionic gonadotropin >3 mIU/mL (n= 115) were included. Human chorionic gonadotropin was measured 11 days after embryo transfer in a single laboratory (coefficient of variation <6%). Surplus frozen serum (-80oC) was shipped to Quest Laboratories for measurement of hyperglycosylated human chorionic gonadotropin (coefficient of variation <9.1%). Linear regression analyses adjusted for oocyte age a priori were used to compare human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin in ongoing pregnancies (>8 weeks of gestation) and failed pregnancies (clinical pregnancy loss, biochemical and ectopic pregnancies). A total of 85 pregnancies (73.9%) were ongoing. Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated (Pearson correlation coefficient 92.14, P < .0001), and mean values of both were positively correlated with blastocyst expansion score (P value test for trend <.0004). Mean human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin were significantly higher in ongoing vs failed pregnancies. Among ongoing pregnancies vs clinical losses, mean hyperglycosylated human chorionic gonadotropin, but not human chorionic gonadotropin, was significantly higher (19.0 vs 12.2 ng/mL, β-8.1, 95% confidence interval-13.0 to-3.2), and hyperglycosylated human chorionic gonadotropin comprised a higher proportion of total human chorionic gonadotropin (4.6% vs 4.1%; risk ratio, 0.79; 95% confidence interval, 0.66-0.94). Measured 11 days after single blastocyst transfer, hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated, but only mean hyperglycosylated human chorionic gonadotropin and its ratio to total human chorionic gonadotropin were significantly higher in ongoing pregnancies vs clinical pregnancy losses. Further evaluation of hyperglycosylated human chorionic gonadotropin, including in multiple embryo transfers and multiple pregnancy, and using serial measurements, is required.

A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer.

Clinical practice guidelines for the management of germ cell tumors recommend the measurements of human chorionic gonadotropin (hCG) and/or free hCGβ subunit for earlier diagnosis/recognition of the residual disease, for the prognostic evaluation and for the post-chemotherapy surveillance. However, the marketed hCG assays are validated and approved only for pregnancy purposes, with the sole exception of the Elecsys 'hCG+β' assay (Roche Diagnostics), cleared in Europe for oncological application. Theoretically, the hCG assay design for oncological purposes should fulfil the recommendations of the International Society of Oncology and Biomarkers requiring the use of antibodies displaying an equimolar recognition of both intact hCG and hCGβ monomer. Further analytical requirements should also be considered, such as optimal analytical sensitivity to allow an early tumor detection and low cross-reactivity for luteinizing hormone (LH). For the Elecsys assay, the detection limit (0.2 U/L) and the reported cross-reactivity for LH (0.12%) may be considered adequate if compared with the recommended requirements. Another issue is the definition of decision limits for oncologic purposes. After 3 years of clinical experience using the Elecsys assay in the oncology setting, we were able to define limits partitioned by sex and age as follows: males <50 years, 0.3 U/L; males >50 years, 2.3 U/L; female <50 years, 2.1 U/L; female >50 years, 5.6 U/L. There is an urgent need to disseminate appropriate educational information and to boost the clinical use of selective, highly sensitive and precise assays, specifically manufactured for cancer application.