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Three Part Question

In [women of childbearing age presenting to the Emergency department with suspected ectopic pregnancy] is [serum or urine beta-hCG] [more sensitive at detecting an ectopic pregnancy]?

Clinical Scenario

A 32 year old woman presents to the emergecny department with vaginal bleeding. You want to know if she is pregnant, and wonder if a urinary pregnancy test is sensitive enough to detect an ectopic pregnancy?

Search Strategy

Medline 1966-2011
Embase 1980-2011
CINAHL 1982-2011
The Cochrane Library


[Exp. Chorionic gonadotropin OR HCG.ti,ab OR "Human chorionic gonadotropin".ti,ab]
AND
["Ectopic Pregnanc*".ti,ab OR "extrauterine pregnanc*".ti,ab OR "extra uterine pregnanc*".ti,ab OR "ovarian pregnanc*".ti,ab OR "tubal pregnanc*".ti,ab]

AND

[exp SERUM/ OR serum.ti,ab]

[exp URINE/ OR urine.ti,ab]

LIMIT to humans and english language)
Cochrane 'ectopic pregnancy' AND 'beta-hCG'
References were checked for additional papers

Search Outcome

69 papers were found using medline. Of these 32 were irrelevant, 22 used inadequate hCG assays (<100iu/L)15 papers were used in the final analysis. No extra papers found using the other databases.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Kingdom et al, 1991, UK	n = 130 Women presenting to Emergency department with pain/bleeding	Prospective study comparing Urine (Clearview - 50iu/L) with quantative serum assay in patients with histologically confirmed ectopic pregnancies	Ectopic Pregnancies n = 12	Sensitivity 100% (12/12)	Industry sponsored. No follow up of negative samples and no statistical analysis
Steier JA. Myking OL 1986 Sweden	n = 46 Patients with 'suspected pathological pregnancy'	Compared performance of new urine hCG assay (ModEL urine hCG 50iu/L) with serum assay. Ectopic pregnancies confirmed histologically	Ectopic pregnancies = 9	100 Sensitive (9/9)	Limited documented methodology. No inclusion criteria. No patient sample data (demographics etc). Small numbers
LeMaistre et al, 1987, USA	n = 3790 unselected patients with 'History or clinical findings suggestive of ectopic pregnancy'	Prospective study over an eighteen month period assaying the sensitivity of Urine hCG (Tandom Icon 50iu/l. Serum analsysis was undertaken on all and ectopic pregnancy was confirmed surgically/histologically	Ectopic Pregnancies = 142	Sensitivity 98.5%(140/142)	Full results not reported. Industry sponsored
Nordenskjold et al, 1985, Sweden	1. 107 consecutive patients over 3 months 'Patients requiring immeadiates surgery excluded' 2. 113 patients treated for ectopic pregnancy over a 13 month period	Two studies. The first study assessed the sensitivity of a urine hCG test (Neo-Pregnosticon75 40iu/L) in an un-selected patient group. The second assessed the sensitivity of the Neo-Pregnosticon 75 in 94 surgically confirmed ectopic pregnancies	Total of 99 Ectopic Pregnancies	Sensitivity 95% (95/99)	Non-ELISA urine hCG assay so arguably not comparable. Incomplete quantative serum data collected. Limited methodology
Tsokos et al, 1986, Australia	n = 101 Patients presenting to the women's hosptial	Consecutive, prospective study looking at the sensitivity of a urine hCG assay (Tandom ICON 50iu/L). Results compared with serum assays and clinical outcome	Ectopic pregnancies n = 16	Sensitivity 87.5% (14/16)	Inconsistent inclusion criteria. Small numbers, Full breakdown of results not published. No blinding.
Cartwright et al, 1986, USA	n = 884. 'Patients presenting to the emergency department who have a urine and serum hCG performed.	Retrospective chart review compating the performance of a urine hCG assay (Tandom Icon 50iu/L) with serum assays	Ectopic pregnancies - 27	Sensitivity 96.3% (26/27)	Limited inclusion criteria. Retrospective data. Only a minority of patients (45%) had both samples taken.
Norman et al, 1988, South Africa	n = 175 Patients with 'signs and symptoms of ectopic pregnancy'	Prospective study looking at the performance of a urine hCG assay (Tandom Icon 50iu/L). Classified as pregnant if ultrasound postive OR histologically confirmed OR serum assay > 25iu/L	Ectopic pregnacies = 95	100% sensitive (95/95)	May have missed low-level Ectopic pregnancies (hcG <25iu/L). Manufacturer's instructions not followed. No data on patient sample (demographics etc). No blinding
Buck et al, 1987, South Africa	n = 909. Patients with 'signs and symptoms of ectopic pregnancy'. Patients requiring immeadiate surgery not included	Prospective study comparing the performance of a urine hCG (Tandom ICON 50iu/L) with serum assays in ectopic histologically confirmed ectopic pregnancies	Ectopic pregnancies n = 71	Sensitivity 100% (71/71)	No patient demographics included. Manufacturer's instructions not followed.
Wong and Suat, 2000, Singapore	n = 162 Patients with surgically/ultrasound confirmed ectopic pregnancies	Retrospective review of 162 patients with ectopic pregnancies. Assessed the sensitivity of a urine hCG assay (Abbot 25iu/L)	Ectopic pregnancies = 162	Sensitivity 96.9% (157/162)	Possible selection bias. Incomplete data (poor retropective data). Poor follow up. Unusually high ultrasound sensitivity - 98% (Normal 40- 50%). Inconsistent outcome measures
Ankum et al, 1996, Netherlands	n = 686 Patients undergoing diatgnostic or therapeutic laparoscopy.	Retrospective review of changing practice over a 12 year period. Changed to a new style of urine hCG assay (Tandom ICON 50iu/L) mid-study.	Decrease in false negatives	29% to 0%	Full data not given. Simultaneous change in practice from abdominal ultrasound to Trans-vaginal ultrasound - significant confounding factor
			Ectopic Pregnancies = 335	Sensitivity 100% (335/335)
Norman et al, 1986, South Africa	n = 60 Patients with 'clinical signs and symptoms' of ectopic pregnancy. 'Obvious ruptures' were excluded	Prospective study looking at the sensitivity of a urine hCG assay (ModEL 50iu/L). Outcome defined as ectopic OR pregnant OR non - pregnant. Results compared with 3 other (older) pregnancy tests	Ectopic pregnancy n = 32	Sensitivity 100% (32/32)	Very limited methodology. Small numbers Poorly - defined outcome measures
Hofmeyr et al, 1988, South Africa	n = 51. Patients with 'suspected ectopic pregnancy'	Prospective study assessing the sensitivity of a urine hCG assay (Tandom Icon 50iu/L)	Ectopic pregnancies = 6	Sensitivity 100% (6/6)	No inclusion criteria. Small numbers. Possible work-up bias.
Minaretzis et al, 1991, Greece	n = 108 . Patients pre-laparotomy for clincaly suspected ectopic pregnancy.	Prospective study looking at the perfomance of two urine hCG assays (Tanden-visual 50iu/L and ModEL 50iu/L). Quantative serum assay and surgical findings used to define ectopic pregnancy.	Ectopic pregnancy n = 108	Tanden Sensitivity 89.8% (97/108)	No blinding. Only includes surgically managed patients
			Ectopic pregnancy n = 108	ModEL Sensitivity 89.8% (97/108)
Barnes et al, 1985, USA	n = 108 . Patients pre-laparotomy for clincaly suspected ectopic pregnancy	Prospective study looking at the perfomance of two urine hCG assays (Tanden-visual 50iu/L and ModEL 50iu/L). Quantative serum assay and surgical findings used to define ectopic pregnancy.	Ectopic pregnancy n = 108	Tanden Sensitivity 89.8% (97/108)	No blinding. Only includes surgically managed patients
			Ectopic pregnancy n = 108	ModEL Sensitivity 89.8% (97/108)

Comment(s)

Serum is sensitive to a lower level of hCG than urine. It is used as a benchmark in nearly all of the studies and can measure down to levels of <0.1iu/L. Urine hCG is quicker and requires less expensive laboratory equipment. (However the comparative cost of the assay in an established laboratory is similar). The newer urine assays claim to measure to levels of hCG as low as 10iu/l - however the industry data is perhaps not reliable. Urine hCG sensitivity in ectopic pregnancy varies from 87.5 - 100%. Overall the sensitivity is around 96%. Serum hCG is used routinely in the management of pregnancy of unknown origin

Clinical Bottom Line

Urine hCG is around 96% sensitive for ectopic pregnancies. Serum hCG is close to 100% sensitive for ectopic pregnancies. Urine hCG assays are continuing to improve but as ectopic pregnancy is potentially life threatening gynaecological problem and a better alternative is readily available - 96% becomes inadequate. With the availability of timely and cost-effective serum sampling - this is now the gold standard.

References

1. Kingdom JC. Kelly T. MacLean AB et al. Rapid one stop urine test for human chorionic gonadotropin in evaluating suspected complications of early pregnancy. British Medical Journal 1991; 302: 1308 - 1311.
2. Steier JA. Myking OL. Evaluation of new serum and urine tests in cases of suspected pathologic early pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1986;65(5):463-5
3. LeMaistre A, Bracey A, Katz A, et al Role of Quantative Choriogonadotropin Assays in Diagnosis of EP. Clinical Chemistry 1987; 33 (10) 1908 – 1910.
4. Nordenskjöld F, Ahlgren M, Erreth L et al. A sensitive urine pregnancy test as an aid in the diagnosis of EP. Fertility and Sterility 1985; 43 (5) 748 – 752.
5. Tsokos N, Masters AM, Boyne P. Emergency serum and urine HCG analyses with the ‘Tandom ICON’ procedure Aust NZ J Obstet Gynaecol 1986; 26: 284 – 286
6. Cartwright PS, Victory DF, Moore RA, Performance of a new enzyme-linked immunoassay urine pregnancy test for the detection of ectopic gestation. Annals of Emergency Medicine 1986 15 (10) 1198 – 1199
7. Norman RJ, Buck RH, Rom L et al, Blood or urine measurement of human chorionic gonadotropin for detection of EP? A comparative study of quantitative and qualitative methods in both fluids. Obstetrics & Gynaecology 1988; 71 (3/1) 315 – 318
8. Emancipator K, Cadoff EM, Burke MD. Analytical versus clinical sensitivity and specificity in pregnancy testing. Am J Obstet Gynecol 1988; 158 (3): 613 – 616.
9. Buck RH, Gihwala N, Rom L et al. Detection of urinary human chorionic gonadotropin by rapid immunoconcentration method is the first-line test for suspected EP. Fertility and Sterility 1987; 48 (5): 761- 765.
10. Wong E, Suat SO. Ectopic Pregnancy – a diagnostic challenge in the emergency department European Journal of Emergency Medicine 2000; 7: 189 – 194
11. Ankum WM, Hajenius PJ, Schrevel LS et al. Management of suspected EP: Impact of new diagnostic tools in 686 consecutive cases. The Journal of Reproductive Medicine 1996; 41 (10): 724 – 728.
12. Norman RJ, Reddi K, Kemp M, et al. Sensitive urine tests and human chorionic gonadotropin secreted during ectopic pregnancy. British Medical Journal 1986; 292: 590 - 591
13. Hofmeyr GJ, Rodrigues FA, Koll PC. A sensitive bedside urine test for human chorionic gonadotropin in suspected ectopic pregnancy. S Afr Med J 1989; 75: 49 – 50.
14. Minaretzis D, Tsionou C, Tsandoulas E. Clinical evaluation of a sensitive urine pregnancy test in the gynaecological emergencies. European Journal of Obstetrics & Gynecology and Reproductive Biology 1991; 39: 123-126
15. Barnes RB, Roy S, Yee B et al Reliability of urinary pregnancy tests in the diagnosis of ectopic pregnancy. Journal of Reproductive Medicine for the Obstetrician and Gyaecologist 1985; 30 (11): 827 - 831.