Human Chorionic Gonadotropin Isoforms in the Diagnosis of Ectopic Pregnancy

Abstract Background: Early diagnosis of ectopic pregnancy uses ultrasound with serial measurements of total human chorionic gonadotropin (hCG). The objective of this study was to explore the possibility that an isolated measurement of hCG isoforms/subunits rather than total hCG could be used as a single test for ectopic pregnancy. Methods: Total and intact hCG, free hCG β- and α-subunits (hCGβ and -α), and hCG β-core fragment were measured by RIA and IRMA in the serum and urine of 76 women presenting at outpatient emergency departments with a positive pregnancy test, lower abdominal pain, and/or vaginal bleeding. Final diagnoses were based on outcomes of pregnancies and tissue histology. Results: Twenty-seven of the 76 women were subsequently diagnosed with viable pregnancies, 37 with spontaneous miscarriage, and 12 with ectopic pregnancy. Concentrations of all forms of hCG were lower in cases of ectopic pregnancy and spontaneous miscarriage than in viable pregnancies. Serum samples gave better results than urine samples. The free hCGβ isoform (P <0.0001) had 100% sensitivity at a specificity of 79% at a 281 pmol/L (6.5 μg/L) cutoff. Total hCG (P = 0.005) had comparable ROC characteristics with a 100% sensitivity and 68% specificity at a cutoff value of 1053 pmol/L (375 IU/L). Neither hCGβ (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from spontaneous miscarriage. Conclusion: Measurement of serum free hCGβ at the time of presentation can identify women with a high probability of ectopic pregnancy who may benefit from closer surveillance, reducing the risk of tubal rupture.

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A Case of Successful Laparoscopic Surgery for Tubal Stump Pregnancy after Tubectomy

Clinical Medicine Insights Case Reports ◽

10.4137/ccrep.s20907 ◽

2015 ◽

Vol 8 ◽

pp. CCRep.S20907 ◽

Cited By ~ 3

Author(s):

Masakazu Nishida ◽

Yuko Miyamoto ◽

Yasushi Kawano ◽

Kanetoshi Takebayashi ◽

Hisashi Narahara

Keyword(s):

Laparoscopic Surgery ◽

Ectopic Pregnancy ◽

Fallopian Tube ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Japanese Woman ◽

Positive Pregnancy Test ◽

Old Japanese ◽

Gestational Sac ◽

Ectopic Pregnancies

The incidence of ectopic pregnancy is approximately 1.3∼2% of all pregnancies, and more than 90% of ectopic pregnancies are detected in the ampulla of the fallopian tube. Ectopic pregnancy occurring in tubal stump after tubectomy is extremely rare, and the frequency of tubal stump pregnancy is approximately 0.4% of all pregnancies. We report one of these rare cases of ectopic pregnancy in a 26-year-old Japanese woman, gravida 4, parity 1. She had undergone laparoscopic tubectomy because of a tubal pregnancy two years ago. She was presented to our hospital with a positive pregnancy test, but no gestational sac was detected in the uterus by echography, even though the level of human chorionic gonadotropin (hCG) in the blood was elevated to 8,900 mIU/mL. Laparoscopic surgery for ectopic pregnancy was performed. During surgery, the position of the pregnancy was found to be in the tubal stump, where tubectomy had already been performed, and the gestational sac was successfully removed. After the surgery, the condition of the patient uneventfully improved and she was discharged from the hospital three days after the surgery. The diagnosis of tubal stump pregnancy is more difficult than that of the more common positions of an ectopic pregnancy in the fallopian tube, and so it is more important to carefully examine the patients with suspected ectopic pregnancy. Laparoscopic surgery is one of the options for tubal stump pregnancy if diagnosed early and if the condition of the patient is stable.

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Lung neoplasm mimicking as ectopic pregnancy due to paraneoplastic secretion of human chorionic gonadotropin: a case report and literature review

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-020-05927-2 ◽

2021 ◽

Author(s):

Jin Peng ◽

Shangge lv ◽

Lin Liu ◽

Shuai Feng ◽

Naidong Xing

Keyword(s):

Systematic Review ◽

Ectopic Pregnancy ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Lung Neoplasm ◽

High Serum ◽

Pregnancy Test ◽

Positive Pregnancy Test ◽

Β Hcg ◽

Present Systematic Review

Abstract Purpose The present systematic review aimed to examine the relationship between lung neoplasm and human chorionic gonadotropin (HCG). Especially, women with lung neoplasm mimicking as ectopic pregnancy were explored. Methods A rare case of lung neoplasm with high serum β-HCG, which was initially thought to be ectopic pregnancy, was reported. A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2020. Results Studies assessed lung neoplasm patients with positive HCG were included. Twenty studies, including 24 patients, were included. These cases illustrate the importance of considering the possibility of paraneoplastic secretion of β-HCG in patients who have a positive pregnancy test. This may prevent a delay in the diagnosis and treatment of malignancy in young women. Of the 24 cases, only 7 (29.17%) were managed surgically; others were managed conservatively or with chemotherapy or radiation. Conclusion The present systematic review shows the need to re-awaken awareness and high index of suspicion to lung neoplasm diagnosis in patients with positive pregnancy test.

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Ectopic pregnancies in disguise: human chorionic gonadotropin (hCG) curves in women with an ectopic pregnancy mimic other outcomes and differ by race and ethnicity

Fertility and Sterility ◽

10.1016/j.fertnstert.2012.07.312 ◽

2012 ◽

Vol 98 (3) ◽

pp. S86

Author(s):

K.E. Dillon ◽

V.D. Sioulas ◽

K. Chung ◽

M. Sammel ◽

P. Takacs ◽

...

Keyword(s):

Ectopic Pregnancy ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Race And Ethnicity ◽

Ectopic Pregnancies

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Predictive value analysis of measurements of human chorionic gonadotropin, pregnancy specific β1-glycoprotein, placental lactogen, and cystine aminopeptidase for the diagnosis of ectopic pregnancy

Fertility and Sterility ◽

10.1016/s0015-0282(16)46759-2 ◽

1983 ◽

Vol 39 (1) ◽

pp. 62-67 ◽

Cited By ~ 19

Author(s):

Glenn D. Braunstein ◽

Ricardo H. Asch

Keyword(s):

Ectopic Pregnancy ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Predictive Value ◽

Placental Lactogen ◽

Value Analysis

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Serum human chorionic gonadotropin measurement in the diagnosis of ectopic pregnancy when transvaginal sonography is inconclusive

Fertility and Sterility ◽

10.1016/s0015-0282(98)00278-7 ◽

1998 ◽

Vol 70 (5) ◽

pp. 972-981 ◽

Cited By ~ 74

Author(s):

Ben W.J Mol ◽

Petra J Hajenius ◽

Simone Engelsbel ◽

Willem M Ankum ◽

Fulco Van der Veen ◽

...

Keyword(s):

Ectopic Pregnancy ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Transvaginal Sonography

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Clinical Utility of Hyperglycosylated hCG in Serum Taken before Hydatidiform Mole Evacuation to Predict Persistent Trophoblastic Disease

The International Journal of Biological Markers ◽

10.1177/172460080602100107 ◽

2006 ◽

Vol 21 (1) ◽

pp. 45-49 ◽

Cited By ~ 3

Author(s):

H. Ngo Duc ◽

N.E. van Trommel ◽

F.C.G.J. Sweep ◽

L.F.A.G. Massuger ◽

C.M.G. Thomas

Keyword(s):

Diagnostic Accuracy ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Hydatidiform Mole ◽

Subsequent Development ◽

Serum Samples ◽

Roc Curve Analysis ◽

Trophoblastic Disease ◽

Central Registry ◽

Hydatidiform Moles

Objective Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG β-subunit (free hCGβ), “total” hCG (hCG+hCGβ) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGβ/hCG+hCGβ, hCGβ/ITA and hCG+hCGβ/ITA could predict the later development of PTD. Design A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD. Methods Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGβ, total hCG, and ITA. From these analytes we also calculated the ratios hCGβ/hCG+hCGβ, hCGβ/ITA, and hCG+hCGβ/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC >0.9 or <0.1) to poor (AUC 0.4–0.6). Results The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGβ (0.610) and hCG+hCGβ (0.622). Conclusions ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.

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Evaluation of Nicked Human Chorionic Gonadotropin Content in Clinical Specimens by a Specific Immunometric Assay

Clinical Chemistry ◽

10.1093/clinchem/45.1.68 ◽

1999 ◽

Vol 45 (1) ◽

pp. 68-77 ◽

Cited By ~ 10

Author(s):

Galina Kovalevskaya ◽

Steven Birken ◽

Tatsu Kakuma ◽

John Schlatterer ◽

John F O’Connor

Keyword(s):

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Normal Pregnancy ◽

Physical Separation ◽

Vitro Fertilization ◽

Clinical Specimens ◽

Reference Preparation ◽

Ectopic Pregnancies

Abstract We report the development and characterization of an IRMA for the direct measurement of nicked human chorionic gonadotropin (hCGn) in blood and urine. hCGn derived from a reference preparation of hCG used as an immunogen elicits monoclonal antibodies (mAbs) with enhanced recognition of human luteinizing hormone epitopes. The most specific assay for pregnancy hCGn is an IRMA composed of one mAb to choriocarcinoma-derived hCGn (C5) and a second mAb developed from immunization with normal-pregnancy hCGn. This assay was used to evaluate hCGn profiles in normal, in vitro fertilization, Down syndrome, and ectopic pregnancies. In all pregnancies, hCGn was usually present in much lower concentrations than the non-nicked hCG isoform. Our results suggest that some form of physical separation from the overwhelming quantities of non-nicked hCG present in clinical specimens will be required before accurate immunochemical estimations of hCGn can be made.

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Discordant Results in Human Chorionic Gonadotropin Assays

Clinical Chemistry ◽

10.1093/clinchem/38.2.263 ◽

1992 ◽

Vol 38 (2) ◽

pp. 263-270 ◽

Cited By ~ 47

Author(s):

Laurence A Cole ◽

Andrew Kardana

Keyword(s):

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Terminal Segment ◽

Beta Subunit ◽

Alpha Subunit ◽

Individual Sample ◽

Serum Samples ◽

Subunit C ◽

Core Fragment ◽

Alpha Type

Abstract Discordance has been reported in human chorionic gonadotropin (hCG) concentrations measured by different immunoassay kits. We examined the results for 40 serum samples assayed with 10 different hCG immunoassay kits. Results varied considerably. Individual sample results varied by as much as 58-fold. Average results for different kits varied by as much as 1.4-fold for pregnancy (20 samples) and 2.2-fold for trophoblast disease (20 samples) serum. We investigated the causes of this discordance. hCG or hCG beta are general names for mixtures of hCG, hCG alpha, or hCG beta immunoreactive molecules in serum. These mixtures include regular hCG, nicked hCG (missing peptide linkages at beta 44-45 or beta 47-48), carbohydrate variants of hCG, hCG missing the beta-subunit C-terminal segment, free beta-subunit, beta-core fragment, and free alpha-subunit. We prepared standards for each of these major variants and measured their reactivities in the 10 hCG immunoassay kits. Free beta-subunit reactivity varied from nonrecognition (anti-beta:anti-alpha type kits; Hybritech Tandem-R and others) to overrecognition (one kit had five-fold greater affinity for free beta than for hCG). Kits with antibodies to beta-subunit C-terminal segment (Organon NML and others) failed to recognize hCG missing this segment, a component of serum hCG in trophoblast disease. Kits with anti-hCG antibodies (Serono MAIA-clone and others) had minimal recognition of nicked hCG (12%), a component of all serum hCG samples, and consistently gave the lowest values with all serum samples. We conclude that differences in recognition of nicked hCG, free beta, and these other hCG variants cause discordance in hCG immunoassay results.

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