Received on May 16, 2003
Accepted on September 17, 2003

Endocrinology and Metabolism

Human Chorionic Gonadotropin Isoforms in the Diagnosis of Ectopic Pregnancy

¹ Williamson Laboratory, Department of Obstetrics and Gynaecology, Barts and The London Queen Mary School of Medicine, London EC1A 7BE, UK and Centro di Diagnosi Prenatale, Dipartimento di Ginecologia, Ostetricia e Neonatologia, Seconda Università degli Studi di Napoli, Naples, Italy
² Williamson Laboratory, Department of Obstetrics and Gynaecology, Barts and The London Queen Mary School of Medicine, London EC1A 7BE, UK and Diagnostica Medica, Centro di Fisiopatologia della Reproduzione, Mercogliano (AV), Italy
³ Williamson Laboratory, Department of Obstetrics and Gynaecology, Barts and The London Queen Mary School of Medicine, London EC1A 7BE, UK and School of Health and Social Science, Middlesex University, Trent Park, Bramley Road, London, UK
⁴ Williamson Laboratory, Department of Obstetrics and Gynaecology, Barts and The London Queen Mary School of Medicine, London EC1A 7BE, UK
⁵ Centro di Diagnosi Prenatale, Dipartimento di Ginecologia, Ostetricia e Neonatologia, Seconda Università degli Studi di Napoli, Naples, Italy

^* To whom correspondence should be addressed. E-mail: r.k.iles{at}qmul.ac.uk.

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 - and -subunits (hCG and -), and hCG -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 hCG 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 hCG (P = 0.7) nor total hCG (P = 0.4) could distinguish ectopic pregnancies from spontaneous miscarriage.

Conclusion: Measurement of serum free hCG 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.© 2003 American Association for Clinical Chemistry