Single point biochemical measurement algorithm for early diagnosis of ectopic pregnancy

Article

Butler, S., Abban, T., Borrelli, P., Luttoo, J., Kemp, B. and Iles, R. 2013. Single point biochemical measurement algorithm for early diagnosis of ectopic pregnancy. Clinical Biochemistry. 46 (13-14), pp. 1257-1263. https://doi.org/10.1016/j.clinbiochem.2013.06.019
TypeArticle
TitleSingle point biochemical measurement algorithm for early diagnosis of ectopic pregnancy
AuthorsButler, S., Abban, T., Borrelli, P., Luttoo, J., Kemp, B. and Iles, R.
Abstract

Objectives:
Tubal rupture as a result of an ectopic pregnancy is the leading cause of first trimester maternal mortality. Currently, the diagnosis of ectopic pregnancy depends on transvaginal ultrasound and serial serum measurements of human chorionic gonadotrophin (hCG), which requires follow up. The objective of this study was to examine whether single point measurements at presentation could distinguish between women with ectopic pregnancy, viable pregnancy, and spontaneous miscarriage.
Design and methods:
Serum total hCG (hCGt), hyperglycosylated hCG (hCGh), free beta subunit of hCG (hCGβ), progesterone (P), and CA-125 were measured by chemiluminescence immunoassay over a 3 month period in 441 women presenting at the emergency room with abdominal pain and a positive pregnancy test. Patient outcomes were followed and confirmed by histology. 65 samples were excluded due to poor sample storage, or lost to follow up.
Results:
The pregnancy outcomes were 175 viable pregnancies, 175 spontaneous miscarriages, and 26 ectopic pregnancies. A serum hCGt < 3736 mIU/mL cut off was 100% sensitive, with 76% specificity, for distinguishing ectopic pregnancy from viable pregnancy; but did not differentiate spontaneous miscarriage. Serum CA125 < 41.98 U/mL produced 100% sensitivity and 43% specificity in distinguishing ectopic pregnancy from spontaneous miscarriage. Sequential application of hCGt and CA-125 cut off followed by ultrasound could detect 100% of ectopic pregnancies with 87% specificity for all intrauterine pregnancies.
Conclusion:
The combination of serum hCGt < 3736 mIU/mL, followed by CA125 < 41.98 U/mL is a promising algorithm for detecting all ectopic pregnancy at initial presentation.

PublisherElsevier
JournalClinical Biochemistry
ISSN0009-9120
Publication process dates
Deposited07 Nov 2013
Output statusPublished
Digital Object Identifier (DOI)https://doi.org/10.1016/j.clinbiochem.2013.06.019
LanguageEnglish
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Jacoby, E., Kicman, A. and Iles, R. 2003. Identification of post-translational modifications resulting from LH beta polymorphisms by matrix-assisted laser desorption time-of-flight mass spectrometric analysis of pituitary LH beta core fragment. Journal of molecular endocrinology. 30 (2), pp. 239-252. https://doi.org/10.1677/jme.0.0300239
The recently identified homodimeric beta-beta subunit of human chorionic gonadotrophin (hCGbb) is no more biologically active than the free beta subunit (hCGb)
Butler, S. and Iles, R. 2004. The recently identified homodimeric beta-beta subunit of human chorionic gonadotrophin (hCGbb) is no more biologically active than the free beta subunit (hCGb). Tumor Biology. 25 (1-2), pp. 18-23. https://doi.org/10.1159/000077719
Serum amino-terminal propeptide of type 1 procollagen (P1NP) in prostate cancer: a potential predictor of bone metastases and prognosticator for disease progression and survival.
Thurairaja, R., Iles, R., Jefferson, K., McFarlane, J. and Persad, R. 2006. Serum amino-terminal propeptide of type 1 procollagen (P1NP) in prostate cancer: a potential predictor of bone metastases and prognosticator for disease progression and survival. Urologia internationalis. 76 (1), pp. 67-71.
Immunoassay detection of human chorionic gonadotrophin beta (hCGb) expression by prostate cancer is of no clinical significance
Otite, U., Baithun, S., Chinegwundon, F., Nargund, V. and Iles, R. 2006. Immunoassay detection of human chorionic gonadotrophin beta (hCGb) expression by prostate cancer is of no clinical significance. Tumor Biology. 27, pp. 181-186.
Gonadotropins and prostate cancer: revisited.
Thwaini, A., Naase, M., Chinegwundon, F., Baithun, S., Ghali, L., Shergill, I. and Iles, R. 2006. Gonadotropins and prostate cancer: revisited. Urologia internationalis. 77 (4), pp. 289-296. https://doi.org/10.1159/000096330
Ectopic hCGbeta expression by epithelial cancer: malignant behaviour, metastasis and inhibition of tumor cell apoptosis
Iles, R. 2007. Ectopic hCGbeta expression by epithelial cancer: malignant behaviour, metastasis and inhibition of tumor cell apoptosis. Molecular and Cellular Endocrinology. 260-26, pp. 264-270. https://doi.org/10.1016/j.mce.2006.02.019
An introduction to mass spectrometry based proteomics-detection and characterization of gonadotropins and related molecules
Kicman, A., Parkin, M. and Iles, R. 2007. An introduction to mass spectrometry based proteomics-detection and characterization of gonadotropins and related molecules. Molecular and Cellular Endocrinology. 260-26, pp. 212-227. https://doi.org/10.1016/j.mce.2006.02.022
Towards the development of an electrochemical biosensor for hCGβ detection
Kassanos, P., Iles, R., Bayford, R. and Demosthenous, A. 2008. Towards the development of an electrochemical biosensor for hCGβ detection. Physiological Measurement. 29 (6), pp. S241-S254. https://doi.org/10.1088/0967-3334/29/6/S21
The role of glycoprotein hormones in endometrial cancer. (in Part 7: Hormones & hormone receptor)
Bax, C., Davies, S., Chatzaki, E., Butler, S. and Iles, R. 2003. The role of glycoprotein hormones in endometrial cancer. (in Part 7: Hormones & hormone receptor). in: Nishida, M. and Kuramoto, H. (ed.) Cell and molecular biology of endometrial carcinoma. London Springer. pp. 195-206
Molecular cell biology and genetic disorders
Iles, R. 2009. Molecular cell biology and genetic disorders. in: Kumar, P. and Clark, M. (ed.) Kumar & Clark’s clinical medicine. Edinburgh Elsevier Saunders. pp. 19-52
Chapter 1: Basic sciences: the cell.
Iles, R. 2008. Chapter 1: Basic sciences: the cell. in: Nargund, V., Raghavan, D. and Sandler, H. (ed.) Urological oncology. London Springer. pp. 3-36
Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy
Iles, R., Borrelli, P., Butler, S. and Staite, E. 2003. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clinical Chemistry. 49 (12), pp. 2045-2049. https://doi.org/10.1373/clinchem.2003.022095
Enhanced affinity capture MALDI-TOF MS: orientation of an immunoglobulin G using recombinant protein G
Iles, R., Bansal, S., Jacoby, E., Neubert, H., Cowan, D. and Kicman, A. 2002. Enhanced affinity capture MALDI-TOF MS: orientation of an immunoglobulin G using recombinant protein G. Analytical Chemistry. 74 (15), pp. 3677-3683. https://doi.org/10.1021/ac025558z
Identification of placental transforming growth factor-beta and bikunin metabolites as contaminants of pharmaceutical human chorionic gonadotrophin preparations by proteomic techniques
Iles, R., Kicman, A., Malatos, S. and Neubert, H. 2005. Identification of placental transforming growth factor-beta and bikunin metabolites as contaminants of pharmaceutical human chorionic gonadotrophin preparations by proteomic techniques. Molecular and Cellular Proteomics. 4 (7), pp. 984-992. https://doi.org/10.1074/mcp.M500085-MCP200
Ectopic human chorionic gonadotropin beta secretion by epithelial tumors and human chorionic gonadotropin beta-induced apoptosis in Kaposi's sarcoma: is there a connection?
Iles, R. and Butler, S. 2003. Ectopic human chorionic gonadotropin beta secretion by epithelial tumors and human chorionic gonadotropin beta-induced apoptosis in Kaposi's sarcoma: is there a connection? Clinical Cancer Research. 9 (13), pp. 4666-4673.
Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte
Wen, S., Tozer, A., Li, D., Docherty, S., Al-Shawaf, T. and Iles, R. 2008. Human granulosa-lutein cell in vitro production of progesterone, inhibin A, inhibin B, and activin A are dependent on follicular size and not the presence of the oocyte. Fertility and Sterility. 89 (5), pp. 1406-1413. https://doi.org/10.1016/j.fertnstert.2007.03.086
Follicular fluid levels of inhibin A, inhibin B, and activin A levels reflect changes in follicle size but are not independent markers of the oocyte's ability to fertilize
Wen, S., Tozer, A., Butler, S., Bell, C., Docherty, S. and Iles, R. 2006. Follicular fluid levels of inhibin A, inhibin B, and activin A levels reflect changes in follicle size but are not independent markers of the oocyte's ability to fertilize. Fertility and Sterility. 85 (6), pp. 1723-1729. https://doi.org/10.1016/j.fertnstert.2005.11.058
The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome
Tozer, A., Iles, R., Iammarrone, E., Gillott, C., Al-Shawaf, T. and Grudzinskas, J. 2004. The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome. Human Reproduction. 19 (3), pp. 522-528. https://doi.org/10.1093/humrep/deh096
Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF
Tozer, A., Iles, R., Iammarrone, E., Gillott, C., Wen, S., Al-Shawaf, T. and Grudzinskas, J. 2004. Characteristics of populations of granulosa cells from individual follicles in women undergoing 'coasting' during controlled ovarian stimulation (COS) for IVF. Human Reproduction. 19 (11), pp. 2561-2568. https://doi.org/10.1093/humrep/deh487
The free monomeric beta subunit of human chorionic gonadotrophin (hCG beta) and the recently identified homodimeric beta-beta subunit (hCG beta beta) both haveautocrine growth effects
Butler, S. and Iles, R. 2004. The free monomeric beta subunit of human chorionic gonadotrophin (hCG beta) and the recently identified homodimeric beta-beta subunit (hCG beta beta) both haveautocrine growth effects. Tumor Biology. 25 (1-2), pp. 18-23. https://doi.org/10.1159/000077719
Cross-Reaction with luteinizing hormone ß-Core is responsible for the age-dependent increase of immunoreactive ß-Core fragment of human chorionic gonadotropin in women with nonmalignant conditions
Iles, R., Javid, M., Gunn, L. and Chard, T. 1999. Cross-Reaction with luteinizing hormone ß-Core is responsible for the age-dependent increase of immunoreactive ß-Core fragment of human chorionic gonadotropin in women with nonmalignant conditions. Clinical Chemistry. 45 (4), pp. 532-538. https://doi.org/10.1093/clinchem/45.4.532
The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma
Crawford, R., Iles, R., Carter, P., Caldwell, C., Shepherd, J. and Chard, T. 1998. The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma. Journal of Clinical Pathology. 51 (9), pp. 685-688. https://doi.org/10.1136/jcp.51.9.685
Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract
Ind, T., Iles, R., Carter, P., Lowe, D., Shepherd, J., Hudson, C. and Chard, T. 1994. Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract. Journal of Clinical Pathology. 47 (11), pp. 1035-1037. https://doi.org/10.1136/jcp.47.11.1035