Total Human Chorionic Gonadotrophin Research Articles

Total human chorionic gonadotropin is a more suitable diagnostic marker of gestational trophoblastic diseases than the free β-subunit of human chorionic gonadotropin

ObjectivesHuman chorionic gonadotropin (hCG) levels are essential for the management of trophoblastic diseases. This study aimed to compare the sensitivities and relationships of two hCG measurement methods (total hCG and the free β-subunit of hCG) in managing gestational trophoblastic disease (GTD). Design and MethodsWe analyzed data from patients treated for GTD at Chiba University Hospital between 2008 and 2019. We focused on cases where both total hCG (mIU/mL) and the free β-subunit of hCG (ng/mL) were measured on the same day. ResultsOut of 80 patients (mean age 38.9 ± 11.7 years) and 158 measurements, 26 had values below the sensitivity threshold for both tests. Fifty-nine measurements were positive for total hCG but below the sensitivity threshold for the free β-subunit of hCG, whereas only two showed the opposite. Seventy-one measurements were positive for both total hCG and the free β-subunit of hCG. There was a significant correlation between total hCG and the free β-subunit of hCG with both positive values, (r = 0.94, p < 0.001; Spearman's correlation test). Of the 85 measurements with undetectable free β-subunit levels, 26 also had undetectable total hCG levels. However, total hCG was detectable in 59 patients from these cases, with a median value (interquartile range) of 2.9 (1.75–4.9) mIU/mL. ConclusionsIn the management of GTD, the use of the free β-subunit system alone cannot be recommended.

First and second trimester maternal serum markers for prenatal aneuploidy screening: An update on the adjustment factors for race, smoking, and insulin dependent diabetes mellitus

ObjectivesThe concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM. MethodsThe study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups. ResultsThe study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study. ConclusionThe adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately.

Ефективність програм екстракорпорального запліднення (IVF/ICSI) у пацієнток із прогнозованою слабкою відповіддю яєчників

Purpose - to show the effectiveness of in vitro fertilization (IVF) programs in infertile women with a predicted poor ovarian response to stimulation with various gonadotropins and to study the course of pregnancy, childbirth and the condition of their newborns. Materials and methods. The Group І is 75 women, the controlled stimulation of superovulation in which by urinary gonadotropins was performed in the protocol with the use of gonadotropin-releasing hormone antagonist. The Group ІІ (comparison) is 65 women, the stimulation of superovulation in which was carried out according to an analogical scheme with recombinant gonadotropins. Confirmation or exclusion of biochemical pregnancy was carried out by determining the level of total human chorionic gonadotropin in blood serum 14 days after embryo transfer. Data processing was carried out using the Stat Soft Statistica 8.0 software package. Results. The frequency of cancellation of IVF cycle (IVF/ICSI) in the patients of the Group І was reliably lower than among the patients of the Group ІІ: in the Group І it was 2 (2.7%) cases against 8 (12.3%) cases in the Group ІІ (p&lt;0.05). IVF cycle cancellations among the patients of the Group І was reliably lower than among the women of the Group ІІ (OR=0.205; 95% СІ: 0.048-0.87; p&lt;0.05). Embryo transfer procedure was performed for 73 women of the Group І and 57 patients of the Group ІІ. The frequency of pregnancy on the IVF protocol and embryo transfer was 41.1% (30/73) and 36.8% (21/57), respectively. Absence of the further embryo development after implantation (biochemical pregnancy) was registered in 1 (3.3%) woman of the Group І and 1 (4.8%) patient of the Group ІІ. Non-developing pregnancy up to 12 weeks was diagnosed in 2 (6.6%) women of the Group І and 3 (14.2%) patients of the Group ІІ. Pregnancy that occurred after the IVF/ICSI program resulted in childbirth in 24 (32.9%) women out of 73 of the Group І and 13 patients out of 57 (22.8%) of the Group ІІ. Conclusions. In women who underwent the controlled stimulation of superovulation by urinary gonadotropins in the protocol using gonadotropin-releasing hormone antagonist compared to women who underwent the stimulation of superovulation with recombinant gonadotropins according to an analogical scheme, the frequency of pregnancy and completion of pregnancy by childbirth was reliably higher. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

A rare case of 48, XXYY syndrome in Taiwan

A rare case of 48, XXYY syndrome in Taiwan

Prenatal features in Beckwith-Wiedemann syndrome and indications for prenatal testing

BackgroundMost cases of Beckwith-Wiedemann spectrum (BWSp) are diagnosed after birth and few studies evaluated the prenatal phenotype; here, we investigate these aspects in a large series of patients with BWSp.MethodsEighty-nine...

Uterine artery pulsatility index and serum BMP-9 predict resistance to methotrexate therapy in gestational trophoblastic neoplasia: A cohort study

Methotrexate is the most common first-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Uterine artery pulsatility index (UAPI) is an ultrasound marker for tumor vascularity that has been associated with an increased risk of methotrexate resistance. The combination of circulating angiogenic factor levels with UAPI data may improve the capacity of this model to predict chemoresistance. This was a single-center cohort study of women newly diagnosed between January 2008 and June 2012 with low-risk GTN during postmolar surveillance and treated with single-agent methotrexate at Charing Cross Hospital, a UK national center for treatment of gestational trophoblastic disease. Two hundred seventeen women underwent an ultrasound for UAPI measurement prior to initiation of chemotherapy. To examine serologic markers of methotrexate resistance among this cohort, we performed a case-control study using archived serum from 76 patients who could be matched based on prognostic risk score. Serum samples were examined by immunoassay to measure 8 different angiogenic factors (VEGF-A, FGF-basic, PLGF-1, PDGF-BB, EGF, ANGPT2, BMP-9, and ENG). Receiver-operator characteristic area under the curve (AUC) values were calculated for the ability of each analyte to correctly classify patients as methotrexate sensitive (MTX-S) or resistant (MTX-R). Total human chorionic gonadotropin levels were similar between the MTX-S and MTX-R groups. UAPI values were significantly higher in MTX-S (median 1.30 [interquartile range {IQR} = 0.80-1.90]) compared to MTX-R patients (median 0.875 [IQR = 0.60-1.30]; P < 0.0001) with AUC 0.68 (95% confidence interval 0.61-0.76; P < 0.0001). In univariate analysis, only BMP-9 concentrations were significantly different between groups, lower among MTX-S (median of 225 ng/L, IQR = 170-287) compared to MTX-R patients (median 280 ng/L [IQR = 200-339]; P= 0.03). Combining UAPI with BMP-9 concentration improved prediction for chemoresistance with AUC 0.77 (95% confidence interval 0.66-0.88; P < 0.0001). Circulating levels of BMP-9 are elevated in newly diagnosed women with low-risk GTN destined to fail primary methotrexate therapy. A combined test using serum BMP-9 plus UAPI might improve prediction of MTX-R in low-risk GTN.

Risk of Severe Maternal Morbidity or Death in Relation to Prenatal Biochemical Screening: Population-Based Cohort Study

This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97-2.25) and DIA (aRR: 2.33; 95% CI: 1.98-2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum.

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.

How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?

Background Total human chorionic gonadotropin (hCGt) tumour marker testing is regarded as an "off label" application for most commercial methods. We compared four assays in patients with a hCGt tumour marker request. We hypothesised that regression slopes would be altered and that outliers would be more common with tumour marker than with pregnancy samples if the detection of malignancy associated hCG molecular forms differed amongst assays. Further such systematic differences would be obvious and large enough to change clinical management decisions. Results We measured hCGt in 390 samples from 137 females and 253 males with a tumour marker request and 208 pregnancy controls with the following methods: Access Total βhCG, Architect Total-βhCG, Cobas hCG + β and Immulite HCG. The between method regressions determined on tumour marker and pregnancy samples were not significantly different. The outlier rates were similar for male and female tumour marker and the pregnancy groups: 1.6% (95% confidence interval [CI] 0%-3.1%), 2.2% (95% CI 0%-4.7%) and 2.9% (95% CI 0.6%-5.2%). The outliers were randomly distributed amongst the methods and we were confident that they would not adversely influence clinical decisions. Conclusions The hCGt results were clinically equivalent with no systematic difference amongst the four assays.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models

BackgroundThe proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGβ, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort.MethodsWe studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models.ResultsWe found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGβ higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity.ConclusionsAlthough the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts.Trial registrationInternational Standard Randomised Controlled Trial number ISRCTN14030412, Date of registration 6/09/2007, retrospectively registered.

Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition

Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy.

Utility of βhCG monitoring in the follow-up of medical management of miscarriage.

To evaluate the percentage change in total βeta-unit human chorionic gonadotropin (βhCG) levels (%ΔβhCG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13weeks. A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total βhCG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound (TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %ΔβhCG ((baseline βhCG - follow-up βhCG)/baseline βhCG×100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. %ΔβhCG was calculated for cases with βhCG levels within twodays of misoprostol and TVUS; calculation interval determined case number. The median %ΔβhCG for 24 cases with a persistent sac (6-9day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% (IQR: 95.44-98.43); P<0.0001). The median %ΔβhCG for eight cases needing surgery on clinical criteria (5-9day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% (IQR: 64.63-91.15; maximum 94.06) vs 97.68% (IQR: 95.61-98.50); P<0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %ΔβhCG>87% predicted no sac at TVUS. %ΔβhCG>94.5% predicted no surgery on clinical criteria. %ΔβhCG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage.

Proficiency testing of maternal serum prenatal screening in second trimester in China, 2015.

IntroductionPrenatal screening and diagnosis is important for the detection of birth defects and genetic diseases. The nationwide proficiency testing (PT) of maternal serum prenatal screening in second trimester in China has been launched since 2003 and partly reflected the performance of screening laboratories. This study analysed the 2015 PT results to examine the performance of clinical laboratories and different platforms.Materials and methodsFifteen lyophilized samples with different concentrations divided into three panels, were distributed to 613 clinical laboratories in 2015. Acceptable performance was defined as scores more than 80% of acceptable responses with the evaluation criterion of ± 30%. The robust coefficient of variation (CV) was also analysed. Chi-square (χ2) test was used to compare the acceptable performance while Kruskal-Wallis test and Mann-Whitney test were applied to compare the robust CV among analytes and mainstream platforms.ResultsOverall, 605, 61, 214, 416, 303 laboratories submitted effective results for alpha fetoprotein (AFP), total human chorionic gonadotropin (t-hCG), β-hCG, unconjugated estriol (uE3) and free β-hCG. The acceptable performances of AFP (μg/L), AFP (KIU/L), t-hCG, β-hCG, uE3, and free β-hCG were 98.45%, 99.24%, 95.58%, 98.72%, 94.50%, and 98.66%, respectively. The χ2 test indicated significant differences existed in the acceptable performances among different analytes and platforms for uE3. Kruskal-Wallis test and Mann-Whitney test suggested the robust CV differed significantly in different analytes and platforms.ConclusionsThe majority of results were acceptable. However, further effort is needed to achieve the standardization and harmonization among analytes and various platforms, particularly for uE3.

Influence of Behçet's disease on first and second trimester serum screening markers.

Behçet's disease (BD) is a rare and multisystemic vasculitis disease. In this study, we investigated whether BD had any effect on the biochemical components of first and second trimester aneuploidy screening tests. A case-control retrospective study was conducted with 32 pregnant women with BD and 60 healthy pregnant women as controls. All pregnant womens' first trimester maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin and second trimester serum alpha-fetoprotein, unconjugated estriol and total human chorionic gonadotropin levels were examined from medical records. First and second serum screening markers were compared between pregnancies with BD and without. There was no difference in age, body mass index and obstetric history between the groups. No significant difference was observed between the groups in terms of first and second trimester serum screening test results in the absence of aneuploidy or neural tube defect. Gestational age at birth, birth weight and neonatal intensive care admission rate were also similar between the groups. Both first and second serum screening tests for Down syndrome may be recommended to pregnant women with BD without the need to readjust these markers. Pregnancy with BD was not associated with adverse perinatal outcome with respect to gestational age at birth or birth weight.

Comparative study of tumor markers in patients with colorectal carcinoma before and after chemotherapy.

Colorectal carcinoma (CRC), the second leading cause of cancer-related deaths in US, has a rising time-trend in India. Tumour markers in CRC are extensively researched, and there's still debate on their diagnostic and prognostic values. In this hospital-based longitudinal study in north India, 51 male diagnosed CRC cases (pre-chemotherapy) were contrasted against 50 age and sex matched controls. Nine biomarkers: carcinoembryonic antigen (CEA), prolactin (PRL), alfa feto protein (AFP), total human chorionic gonadotropin (hCG), cancer antigen-125 (CA-125), serum testosterone, prostate specific antigen (PSA) and ferritin were measured by direct chemiluminescence technique. Further, follow-up was done on 47 cases after treatment with six cycles of 5-flurouracil (5-FU) and oxaliplatin. Mean serum CEA (case: 5.94±8.27 ng/mL, control: 2.5±0.79 ng/mL, P<0.05), PRL (case: 28.12±13.39 ng/mL, control: 14.24±13.13 ng/mL, P<0.0001), AFP (case: 10.9±6.65 ng/mL, control: 4.02±1.26 ng/mL, P<0.0001) levels were significantly raised in CRC cases compared to controls. On the contrary, mean testosterone level (P<0.05) was lower among the cases. After chemotherapy, the mean serum CEA (P<0.05), AFP (P<0.0001) and CA-125 (P<0.05) levels among the cases decreased significantly compared to their pretreatment levels. The present study strongly indicates the role of CEA, PRL, AFP, CA-125 and testosterone as important biomarkers in male CRC patients from north India. Further, AFP, CA-125 and CEA may be used to assess the effectiveness of chemotherapy in such patients.

Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin (Podcast)

Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin (Podcast)

Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein A and total human chorionic gonadotropin.

This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG). The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n = 129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls. Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM] ≤ the 10th percentile in nulliparous or ≤ the 5th percentile in multiparous) or high total hCG (MoM ≥ the 90th percentile in nulliparous or ≥ the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively). Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia.

First and second trimester maternal serum markers in pregnancies with a vanishing twin.

The aim of this study was to assess the concentration of the first and second trimester maternal serum markers in pregnancies with a vanishing twin. This is a retrospective case-control study of pregnancies screened for Down syndrome in one Ontario center. Singleton pregnancies with ultrasound evidence of a vanishing twin were identified, and each was matched with five normal singleton controls for ethnicity, maternal age, gestational age, and blood sampling date. The median MoM of the first and second trimester serum markers was compared between cases and controls. The differences were assessed using the Mann-Whitney U-test. The study included 174 pregnancies that had a vanishing twin. Compared with control pregnancies, pregnancy associated plasma protein A increased by 21% (p = 0.0026), alpha-fetoprotein (AFP) increased by 10% (p < 0.0001), and dimeric inhibin A (DIA) increased by 13% (p = 0.0470) in pregnancies with a vanishing twin. Unconjugated oestriol and total human chorionic gonadotrophin were not significantly changed in these pregnancies. Pregnancy associated plasma protein A is not an adequate marker for pregnancies with a vanishing twin. The impact of elevated AFP on risk estimation is offset by that of DIA to certain extent. Further studies are needed to establish an adequate adjustment method for AFP and DIA to improve the accuracy of screening results for these pregnancies.

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract

Background:Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables.Methods:We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan–Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ⩾2 IU l−1.Results:A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set.Conclusions:Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

Free β-human Chorionic Gonadotropin, Total Human Chorionic Gonadotropin and Maternal Risk of Breast Cancer

We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information.