Retrospective evaluation of 99th percentile hCG results to adjust clinical decision points

While accurate measurement of chorionic gonadotropin (hCG) is necessary, so are appropriate clinical decision points (CDPs) for patients of all ages. The CDP for hCG is intended to identify early pregnancy in patients of child bearing age; non-pregnant patients who are older frequently yield hCG results > 5 IU/L, making the use of a low hCG CDP problematic for these patients. Using a retrospective review of all hCG results generated over a 32-month period, 8507 hCG results from non-pregnant females of all ages were analyzed. Patients < 40 years of age comprised 74% of hCG measurements, and produced hCG results ≥ 5 IU/L 1% of the time, but this frequency increased in patients 40–49 (17% of hCG results; 4% ≥5 IU/L) and ≥50 (9% of hCG results; 20% ≥ 5 IU/L). While only 3% of hCG results were ≥5 IU/L in the overall data set, all (24/24) of hCG results 10–14 IU/L came from patients ≥ 40 years of age and all (3/3) hCG results ≥ 15 IU/L came from patients ≥ 50 years of age. The 99th percentile hCG results in the population were 3 IU/L in patients < 40, 7 IU/L in patients 40–49, and 13 IU/L in patients ≥ 50 years of age. These findings demonstrate a progressive increase in measurable hCG correlating to patient age and demonstrate a proof-of-concept that institutions could assess 99th percentile hCG results to assign more appropriate method-dependent CDPs to different age groups.     

Total hCG tests

IntroductionThere are 12 types of automated total hCG tests sold today, the Abbott Architect, Abbott AxSym, the Beckman Access 2. Beckman DxI 800, the Ortho Vitros EciQ, Roche Elecsys hCG + β, Siemens ACS180, Siemens Centaur, Siemens Dimension, Siemens Immulite and Siemens Stratus, and the Tosoh A1A. All tests claim to be total hCG tests but do not define what total means. Total hCG test needs to detect all hCG variants in order to be used for all hCG test clinical applications. Here we assess this ability.MethodsCoded samples of pure hCG, nicked hCG, hyperglycosylated hCG, nicked hCG missing C-terminal peptide, nicked hyperglycosylated hCG, asialo hCG, hCGβ, nicked hCGβ and β-core fragment were tested blindly in serum and urine at 10 independent laboratories.ResultsWhile the Siemens Immulite total hCG test detected 8 of 9 hCG variant standards, other assays poorly detected important determinants such as nicked hCG missing the C-terminal peptide, β-core fragment, hyperglycosylated hCG, nicked hCG, asialo hCG, and hCGβ. Four assay appropriately detected 4 of 9 variants, 2 assays detected 3 of 9, 4 assays detected 2 of 9 and 1 assay only appropriately detected 1 of 7 hCG variants.DiscussionCare is needed in selecting a total hCG test. The Siemens Immulite tests performed best at detecting all the hCG variants making it appropriate for all applications. Nine assays had limited applications, 3 of the assays were appropriate for advanced pregnancy testing only.     

Monozygotic twins discordant for body stalk anomaly.

We report on two cases of monozygotic twins discordant for body stalk anomaly, diagnosed prenatally in a multicenter ultrasound screening study at 10-14 weeks of gestation. Ultrasound showed a large abdominal wall defect with most of the abdominal contents and almost half of the body in the celomic cavity, in association with severe kyphoscoliosis and a very short umbilical cord. Both pregnancies were managed expectantly and delivered by Cesarean section. The abnormal babies died soon after birth and autopsy confirmed the sonographic diagnosis. Body stalk anomaly in twins is extremely rare. These are, to our knowledge, the first cases reported on monozygotic twins discordant for this anomaly, indicating that the incomplete twinning theory cannot uniformly explain the pathogenesis of the body stalk in twins.     

Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C

BACKGROUND: The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. METHODS: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. RESULTS: Only 74 of 537 patients (14%) had a biopsy size > or =25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False positives of fibrosis staging (3.5%) were associated with fragmented biopsies. CONCLUSION: In this series, the size of liver biopsy is adequate in only a minor proportion (approximately 14%) of patients with chronic hepatitis C. When biopsy and marker results are discordant, a reason can be identified in more than two-thirds of cases and, in those cases, biopsy failure is >7 times more common than diagnostic failure of markers.     

The need for a quantitative urine hCG assay

BackgroundThe USA uniquely does not use quantitative urine human chorionic gonadotropin (hCG) tests despite being invaluable in pregnancy testing and in monitoring cancer patients. We look at current hCG tests and their detection of the degraded forms of hCG predominant in urine. We examine levels of urinary hCG, its usefulness in pregnancy testing, and advantages of urine testing in false positive hCG cases and cancer cases.MethodshCG assays were blindly evaluated at 10 laboratories running different methodologies. Daily urine samples from 164 women were collected through 5 menstrual cycles or until pregnancy was achieved. Urines were assayed for total hCG. We also examined the use of quantitative urine hCG in confirming false positive serum hCG results in 80 clinical cases.ResultsOnly the Siemens Immulite test was shown to detect the degraded forms of hCG present in urine. This test equally recognized urine and serum hCG. We investigated background hCG in 9026 urines, the mean hCG level was 0.04 IU/L, and the 99th centile was 1.4 IU/L. In cycles where pregnancy was achieved, hCG could be detected in urine at 24.6 days of a 28.7 day menstrual cycle. At this time, the average hCG was 6.02 IU/L, setting a sensitivity level for quantitative urine hCG tests to detect pregnancy. Quantitative urinary hCG proved critical in detecting cancer in 3 of 80 cases complicated by false positive serum hCG.ConclusionsThe need for a quantitative urine hCG assay is undeniable and we invite manufacturers to produce a quantitative urine hCG test.     

hCG, five independent molecules

INTRODUCTION: The hCG amino acid sequence supports 5 glycoproteins. All are called hCG forms. This review examines all 5 molecules, the hormone as produced by the placental syncytiotrophoblast cells, the sulfated hormone produced by the pituitary gonadotrope cells, the hyperglycosylated hCG autocrine made by placental cytotrophoblast cells, and the autocrine cancer promoters hyperglycosylated hCG, hCG? and hyperglycosylated hCG? as made by all malignancies. This review examines all the molecules and multiple proven functions, ranging from evolution to cancer promotion to hormone action. RESULTS AND DISCUSSION: hCG forms are critical super-growth factors in humans, with an exceptional wide range of functions.     

Procedure for pregnancy testing

This article summarises the procedure for assessing and undertaking a test to determine if a woman is pregnant.     

Pregnancy in a discordant couple

An HIV-discordant couple repeatedly failed to conceive through in vitro fertilization. Following the death of the HIV-positive father, embryo transfer resulted in pregnancy and birth of an HIV-negative child.     

Human choriogonadotropin (hCG): comparisons between determinations of intact hCG, free hCG beta-subunit, and "total" hCG + beta in serum during the first half of high-risk pregnancy.

We have studied the concentrations of intact human choriogonadotropin (hCG) and the free hCG beta-subunit in blood samples from singleton pregnancies at risk for habitual or threatened abortion. The samples were obtained weekly between the 6th and 12th weeks and in the 14th and 16th weeks of gestational age. The concentrations of intact hCG, of the free hCG beta-subunit, and of "total" hCG (i.e., intact hCG and the free hCG beta-subunit: hCG + beta) were measured in serum by specific immunoassays. The distributional statistics (the 5th, 50th, and 95th percentiles) of "total" hCG + beta and of intact hCG showed very similar patterns, whereas the response curves for the free hCG beta-subunit showed very much lower serum concentrations. From these data we also estimated distributional statistics of the percent molar ratios of free hCG beta-subunit to intact hCG. We conclude that (a) the relatively small proportion of free hCG beta-subunit in serum during the first half of singleton pregnancy is far too low to interfere with the applied "total" hCG assay, as compared with the serum values obtained for intact hCG, and (b) the percent molar ratios of free hCG beta-subunit to intact hCG, or to "total" hCG + beta, never exceeded 1.0% throughout the period of pregnancy studied.     

胎膜早破阴道后穹窿冲洗液β—hCG测定

探讨阴道后穹隆冲洗液β-hCG水平测定对于诊断胎膜早破(PROM)的意义。方法 采用放射免疫法测定30例胎膜早破孕妇(胎膜早破组)和60例正常孕妇(对照组,其中30例妊娠28～32周为对照组1,30例妊娠36～42周为对照组2)后穹隆冲洗液(3ml无菌生理盐水)β-hCG水平。结果 胎膜早破组后穹窿冲洗液β-hCG测定结果为324.82mlU/ml,观察组后穹窿冲洗液β-hCG测定结果为5.36mlU/ml,观察组后穹隆冲洗液β-hCG水平明显高于对照组,差异有显著性(P<0.01)。对照组1 β-hCG测定结果为6.14ml/Uml,对照组2 β-hCG测定结果为4.66mIU/ml,无显著差异(P>0.05)。结论 妊娠中晚期与妊娠晚期阴道后穹隆冲洗液β-hCG水平测定无显著差异:阴道后穹隆冲洗液β-hCG水于测定可作为胎膜早破的诊断指标之一。     

Identical twins discordant for ulcerative colitis with colon cancer.

A 22-year-old patient with a 16-year history of ulcerative colitis who developed multifocal anaplastic colon cancer is presented. His identical twin, proven by blood type, HL-A, and fingerprint analyses, has been completely asymptomatic. This report suggests that ulcerative colitis results from a polygenic predisposition without full penetrance. Subsequent development of colon cancer seems more likely related to the inflammatory disease that an independent genetic determinant.     

Three-dimensional sonographic features of discordant twins

Three-dimensional sonography clearly revealed significant antenatal differences in size in three pairs of fetal twins. The benefits and advantages of the use of three-dimensional sonography to visualize discordant twins in utero are visual recognition of difference in fetal size and complete impression of fetal interrelationships.     

Procedure for Trichomonas vaginalis cultivation

The investigation was undertaken to design a nutrient medium that could reduce the duration of a culture test in the diagnosis of trichomoniasis and to comparatively evaluate its effectiveness. A procedure was proposed to cultivate Trichomonas vaginalis, which was based on the use of the nutrient medium containing casein hydrolysate, yeast autolysate, and serum, added by 0.6 ml of liquid Ferrum Lec (iron (III) hydroxide polyisomaltose), which reduced the time taken to identify Trichomonas vaginalis (on day 2). At the same time, the higher content of iron [III] hydroxide with polyisomaltose was shown to produce no positive effect.