Table G.11What is the diagnostic accuracy of two or more hCG measurements plus progesterone for determining a viable intrauterine pregnancy in women with pain and bleeding and pregnancy of unknown location?

Bibliographic informationReason for exclusion
Achiron,R., Schwartz,S., Zakut,H., Diagnostic value of ultrasound scanning and beta-human chorionic gonadotropin in stable patients suspected of ectopic pregnancy, Israel Journal of Medical Sciences, 22, 594-596, 1986Wrong test - does not assess the rate of change of hCG
Adoni,A., Milwidsky,A., Hurwitz,A., Palti,Z., Declining beta-HCG levels: an indicator for expectant approach in ectopic pregnancy, International Journal of Fertility, 31, 40-42, 1986No relevant outcomes reported - patterns of hCG are evaluated for the choice of management approach, not for the diagnosis of pregnancy outcome.
Alhamdan,D., Bignardi,T., Casikar,I., Riemke,J., Condous,G., Pre-treatment human chorionic gonadotrophin (hCG) ratio in the management of non-tubal ectopic pregnancy, Ceylon Medical Journal, 56, 70-71, 2011Single case report
Altay,M.M., Yaz,H., Haberal,A., The assessment of the gestational sac diameter, crown-rump length, progesterone and fetal heart rate measurements at the 10th gestational week to predict the spontaneous abortion risk, Journal of Obstetrics and Gynaecology Research, 35, 287-292, 2009Wrong population - excludes women with pain and bleeding; only reports diagnostic accuracy of progesterone
Banerjee,S., Aslam,N., Zosmer,N., Woelfer,B., Jurkovic,D., The expectant management of women with early pregnancy of unknown location, Ultrasound in Obstetrics and Gynecology, 14, 231-236, 1999Wrong test - model incorporates serum hCG level, not rate of change of hCG.
Barnhart,K.T., Casanova,B., Sammel,M.D., Timbers,K., Chung,K., Kulp,J.L., Prediction of location of a symptomatic early gestation based solely on clinical presentation, Obstetrics and Gynecology, 112, 1319-1326, 2008Wrong test - model included hCG level only, not the pattern of change in hCG; progesterone measurements are not reported
Bignardi,T., Condous,G., Kirk,E., Van Calster,B., Van Huffel,S., Timmerman,D., Bourne,T., Viability of intrauterine pregnancy in women with pregnancy of unknown location: prediction using human chorionic gonadotropin ratio vs. progesterone, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 35, 656-661, 2010Wrong study population - only includes women with an intrauterine pregnancy of uncertain viability; therefore does not match the presenting population (PUL) for this review
Buck,R.H., Joubert,S.M., Norman,R.J., Serum progesterone in the diagnosis of ectopic pregnancy: a valuable diagnostic test?, Fertility and Sterility, 50, 752-755, 1988Wrong test - reports diagnostic accuracy of progesterone alone
Cacciatore,B., Early diagnosis of ectopic pregnancy by ultrasonography and quantitative determinations of serum hCG, Acta Obstetricia et Gynecologica Scandinavica, 70, 633-638, 1991Wrong test - uses discriminatory zone of hCG only; no progesterone
Catania,V., Murgia,F., Non invasive diagnosis and therapy of ectopic pregnancy, Giornale Italiano di Ostetricia e Ginecologia, 15, 513-515, 1993No relevant outcomes reported - evaluates hCG declines following treatment with methotrexate, not the use of hCG levels for diagnosis
Chung,K., Chandavarkar,U., Opper,N., Barnhart,K., Reevaluating the role of dilation and curettage in the diagnosis of pregnancy of unknown location, Fertility and Sterility, 96, 659-662, 2011Progesterone was not measured and all of the study population underwent D&C for suspected EP; therefore there was no gold standard diagnosis of any potentially viable IUP.
Condous,G., Okaro,E., Khalid,A., Bourne,T., Do we need to follow up complete miscarriages with serum human chorionic gonadotrophin levels?, BJOG: An International Journal of Obstetrics and Gynaecology, 112, 827-829, 2005Wrong population - this study only includes women diagnosed with a complete miscarriage
Condous,G., Okaro,E., Khalid,A., Lu,C., Van Huffel,S., Timmerman,D., Bourne,T., A prospective evaluation of a single-visit strategy to manage pregnancies of unknown location, Human Reproduction, #20, 1398-1403, 2005Wrong test - evaluates a single visit strategy and therefore does not use serial hCG measurements
Condous,G., Okaro,E., Khalid,A., Timmerman,D., Lu,C., Zhou,Y., Van Huffel,S., Bourne,T., The use of a new logistic regression model for predicting the outcome of pregnancies of unknown location, Human Reproduction, #19, -1910, 2004Both viable and non-viable intrauterine pregnancies are included in the “IUP” group, and cannot be distinguished
Condous,G., Van Calster,B., Kirk,E., Haider,Z., Timmerman,D., Van Huffel,S., Bourne,T., Prediction of ectopic pregnancy in women with a pregnancy of unknown location, Ultrasound in Obstetrics and Gynecology, 29, 680-687, 2007Wrong test - model M4 does not incorporate progesterone; viable and non-viable intrauterine pregnancies cannot be distinguished
Condous,G., Van Calster,B., Kirk,E., Timmerman,D., Van Huffel,S., Bourne,T., Prospective cross-validation of three methods of predicting failing pregnancies of unknown location, Human Reproduction, 22, 1156-1160, 2007No relevant outcomes reported - diagnostic accuracy is only reported for the diagnosis of failing pregnancies of unknown location
Dart,R., Ramanujam,P., Dart,L., Progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate, American Journal of Emergency Medicine, 20, 575-579, 2002Wrong test - reports diagnostic accuracy of progesterone only, not in conjunction with hCG
Day,A., Sawyer,E., Mavrelos,D., Tailor,A., Helmy,S., Jurkovic,D., Use of serum progesterone measurements to reduce need for follow-up in women with pregnancies of unknown location, Ultrasound in Obstetrics and Gynecology, 33, 704-710, 2009Wrong test - reports the use of progesterone in conjunction with a single hCG threshold, not the rate of change of hCG
El Bishry,G., Ganta,S., The role of single serum progesterone measurement in conjunction with betahCG in the management of suspected ectopic pregnancy, Journal of Obstetrics and Gynaecology, 28, 413-417, 2008Wrong test - reports diagnostic accuracy of progesterone only, not all women had a serial hCG measurement
Elson,J., Salim,R., Tailor,A., Banerjee,S., Zosmer,N., Jurkovic,D., Prediction of early pregnancy viability in the absence of an ultrasonically detectable embryo, Ultrasound in Obstetrics and Gynecology, 21, 57-61, 2003Wrong population - participants all have intrauterine gestation sac visualised
Eriksen,B.C., Eik-Nes,S.H., Prognostic value of ultrasound, HCG and progesterone in threatened abortion, Journal of Clinical Ultrasound, 14, 3-9, 1986Wrong test - uses single value of hCG; excludes women with ectopic pregnancies
Florio,P., Severi,F.M., Bocchi,C., Luisi,S., Mazzini,M., Danero,S., Torricelli,M., Petraglia,F., Single serum activin a testing to predict ectopic pregnancy, Journal of Clinical Endocrinology and Metabolism, 92, 1748-1753, 2007Wrong test - reports accuracy of single hCG and progesterone levels only
Gevaert,O., De Smet,F., Kirk,E., Van Calster,B., Bourne,T., Van Huffel,S., Moreau,Y., Timmerman,D., De Moor,B., Condous,G., Predicting the outcome of pregnancies of unknown location: Bayesian networks with expert prior information compared to logistic regression, Human Reproduction, 21, 1824-1831, 2006Diagnostic accuracy for the diagnosis of viable intrauterine pregnancies is not reported
Gracia,C.R., Barnhart,K.T., Diagnosing ectopic pregnancy: decision analysis comparing six strategies, Obstetrics and Gynecology, 97, 464-470, 2001Wrong population - modelling and results are based on a hypothetical cohort only
Graczykowski,J.W., Seifer,D.B., Diagnosis of acute and persistent ectopic pregnancy, Clinical Obstetrics and Gynecology, 42, 9-22, 1999Non-systematic review.
Guerriero,S., Mais,V., Ajossa,S., Paoletti,A.M., Risalvato,A., Melis,G.B., The screening of embryonic viability in early asymptomatic pregnancy by a single endosonographic scan associated with plasma human chorionic gonadotropin determination, Journal of Assisted Reproduction and Genetics, 11, 346-352, 1994Wrong population - participants were asymptomatic, those with bleeding were excluded
Hahlin,M., Thorburn,J., Bryman,I., The expectant management of early pregnancies of uncertain site, Human Reproduction, 10, 1223-1227, 1995Wrong outcome - reports hormonal predictors of spontaneous resolution of pregnancy, in a sub-set of women selected for expectant management
Jakiel,G., Wieczorek,P., Bokiniec,M., Bakalczuk,S., Ectopic pregnancy diagnosis in very high risk patients, Ginekologia Polska, 69, 575-579, 1998Wrong test - this study uses a positive or negative hCG test, not the results of serial measurements
Katsikis,I., Rousso,D., Farmakiotis,D., Kourtis,A., amanti-Kandarakis,E., Panidis,D., Receiver operator characteristics and diagnostic value of progesterone and CA-125 in the prediction of ectopic and abortive intrauterine gestations, European Journal of Obstetrics, Gynecology, and Reproductive Biology, 125, 226-232, 2006Wrong test - reports diagnostic accuracy of progesterone and CA-125 only
Kirk,E., Condous,G., Van Calster, B., Van Huffel, S., Timmerman,D., Bourne,T., Rationalizing the follow-up of pregnancies of unknown location, Human Reproduction, 22, 1744-1750, 2007Wrong test - model does not incorporate progesterone.
Koh,G.H., Yeo,G.S., Diagnosis of ectopic pregnancy--why we need a protocol, Singapore Medical Journal, 38, 369-374, 1997This is an audit of a protocol, not a diagnostic accuracy study.
Kuscu,E., Vicdan,K., Turhan,N.O., Oguz,S., Zorlu,G., Gokmen,O., The hormonal profile in ectopic pregnancies, JPMA - Journal of the Pakistan Medical Association, 44, 45-47, 1994Wrong test - single serum hCG and progesterone
Kuscu,E., Vicdan,K., Turhan,N.O., Oguz,S., Zorlu,G., Gokmen,O., The hormonal profile in ectopic pregnancies, Materia Medica Polona, 25, 149-152, 1993Wrong test - single serum hCG and progesterone
Lautmann,K., Cordina,M., Elson,J., Johns,J., Schramm-Gajraj,K., Ross,J.A., Clinical use of a model to predict the viability of early intrauterine pregnancies when no embryo is visible on ultrasound, Human Reproduction, 26, 2957-2963, 2011Wrong study population - only includes women with an intrauterine pregnancy of uncertain viability; therefore does not match the presenting population (PUL) for this review
Ledger,W.L., Sweeting,V.M., Chatterjee,S., Rapid diagnosis of early ectopic pregnancy in an emergency gynaecology service--are measurements of progesterone, intact and free beta human chorionic gonadotrophin helpful?, Human Reproduction, 9, 157-160, 1994Wrong test - uses a single value of hCG and progesterone
Lindblom,B., Hahlin,M., Lindblom,P., Serial human chorionic gonadotropin determinations by fluoroimmunoassay for differentiation between intrauterine and ectopic gestation, American Journal of Obstetrics and Gynecology, 161, 397-400, 1989The use of progesterone is not reported. Serial hCG is only used for diagnosing a small proportion of women, who are not the correct presenting population.
Long,C.A., Lincoln,S.R., Whitworth,N.S., Cowan,B.D., Serum progesterone predicts abnormal gestations in clomiphene citrate conception cycles as well as in spontaneous conception cycles, Fertility and Sterility, 61, 838-842, 1994Wrong test - reports diagnostic accuracy of progesterone alone
McCord,M.L., Muram,D., Buster,J.E., Arheart,K.L., Stovall,T.G., Carson,S.A., Single serum progesterone as a screen for ectopic pregnancy: Exchanging specificity and sensitivity to obtain optimal test performance, Fertility and Sterility, 66, 513-516, 1996Wrong test - reports diagnostic accuracy of progesterone only, not in conjunction with hCG
Ozates,B., Caglar,G.S., Kalyoncu,S., Yildiz,Y., Aktan,A., Mollamahmutoglu,L., The assessment of anticardiolipin antibodies in ectopic pregnancies, Gazzetta Medica Italiana Archivio per le Scienze Mediche, 165, 221-225, 2006Wrong population - women are presenting for an elective abortion, not due to pain and bleeding. No diagnostic accuracy measures are reported for hCG and progesterone, only for IgM.
Plante,B.J., Blume,J.D., Lambert-Messerlian,G., Shackelton,R., Canick,J., Phipps,M.G., A multiple marker model to predict pregnancy viability when progesterone is indeterminate, Journal of Reproductive Medicine, 53, 243-249, 2008Wrong test - this paper reports diagnostic accuracy of a model incorporating hCG level, not the rate of change of hCG.
Rode,L., Daugaard,G., Fenger,M., Hilsted,L., Krag Moller,L., Raaberg,L., Ottesen,B., Serum-hCG: Still a problematic marker, Acta Obstetricia et Gynecologica Scandinavica, 82, -200, 2003This paper is a case report of two patients, not a diagnostic accuracy study
Santiago-San,JuanF, Casals,M.E., Karunungan,E., Mochizuki,M., The use of human chorionic gonadotropin and ultrasound in the early diagnosis of ectopic pregnancy: A prospective study, ICMR Annals, 7, -250, 1987Wrong test - this study uses a urinary hCG test
Sauer,M.V., Anderson,R.E., Vermesh,M., Stone,B.A., Paulson,R.J., Spontaneously resorbing ectopic pregnancy: preservation of human chorionic gonadotropin bioactivity despite declining steroid hormone levels, American Journal of Obstetrics and Gynecology, 161, 1673-1676, 1989Reports means only, no measures of diagnostic accuracy
Shaunik,A., Kulp,J., Appleby,D.H., Sammel,M.D., Barnhart,K.T., Utility of dilation and curettage in the diagnosis of pregnancy of unknown location, American Journal of Obstetrics and Gynecology, 204, 130-130, 2011Wrong test - the use of progesterone is not reported
Spitzer,M., Pinto,A.B.M., Dasgupta,R., Benjamin,F., Early diagnosis of ectopic pregnancy: Can we do it accurately using a biochemical profile?, Journal of Women's Health and Gender-Based Medicine, 9, 537-Based, 2000Wrong test - diagnostic accuracy is only reported for CPK/progesterone ratio
Sterzik,K., Rosenbusch,B., Benz,R., Serum specific protein 1 and beta-human chorionic gonadotropin concentrations in patients with suspected ectopic pregnancies, International Journal of Gynaecology and Obstetrics, 28, 253-256, 1989Wrong test - single measurement of hCG and progesterone
Stewart,B.K., Nazar-Stewart,V., Toivola,B., Biochemical discrimination of pathologic pregnancy from early, normal intrauterine gestation in symptomatic patients, American Journal of Clinical Pathology, 103, 386-390, 1995No relevant outcomes reported - diagnostic accuracy is reported for progesterone separately, not in conjunction with serial hCG
Stovall,T.G., Ling,F.W., Cope,B.J., Buster,J.E., Preventing ruptured ectopic pregnancy with a single serum progesterone, American Journal of Obstetrics and Gynecology, 160, 1425-1428, 1989Wrong test - does not report diagnostic accuracy of progesterone in conjunction with serial serum hCG
Thorburn,J., Bryman,I., Hahlin,M., Lindblom,B., Differential diagnosis of early human pregnancies: impact of different diagnostic measures, Gynecologic and Obstetric Investigation, 33, 216-220, 1992No relevant outcomes reported - does not report diagnostic accuracy for progesterone
Valley,V.T., Mateer,J.R., Aiman,E.J., Thoma,M.E., Phelan,M.B., Serum progesterone and endovaginal sonography by emergency physicians in the evaluation of ectopic pregnancy, Academic Emergency Medicine, 5, 309-313, 1998Wrong test - reports diagnostic accuracy of progesterone alone
Westergaard,J.G., Teisner,B., Sinosich,M.J., Madsen,L.T., Grudzinskas,J.G., Does ultrasound examination render biochemical tests obsolete in the prediction of early pregnancy failure?, British Journal of Obstetrics and Gynaecology, 92, 77-83, 1985Wrong test - diagnostic accuracy is not reported for the change in hCG, only for single levels of hCG and progesterone

From: Appendix G, Excluded studies

Cover of Ectopic Pregnancy and Miscarriage
Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage.
NICE Clinical Guidelines, No. 154.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG; 2012 Dec.
Copyright © 2012, National Collaborating Centre for Women's and Children's Health.

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