Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: A systematic review and meta-analysis

N. M. van Mello*, F. Mol, B. C. Opmeer, W. M. Ankum, K. Barnhart, A. Coomarasamy, B. W. Mol, F. van der Veen, P. J. Hajenius

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Background: The term 'pregnancy of unknown location' (PUL) refers to cases where a pregnancy test is positive but the pregnancy cannot be visualized by transvaginal sonography (TVS). Various strategies integrating TVS and serum hCG measures are used to follow-up until the location and/or viability of the pregnancy becomes clear; however, the optimal strategy to predict the outcome of pregnancy in women with PUL is unknown. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic accuracy of the various serum hCG strategies in women with PUL. Methods: We searched Medline and EMBASE for articles which were published (in any language) from 1980 to January 2012 on strategies using serum hCG in women with PUL and reporting on the final outcome of pregnancy. Results: From 980 selected titles, 23 articles, all cohort studies, were included. There were 10 studies on a single serum hCG cut-off level, 4 on serum hCG ratio (hCG 48 h/hCG 0 h) and 6 on logistic regression modelling. Three other strategies were reported using serum hCG, serum progesterone and/or uterine curettage findings; each of these strategies comprised a single study. Comparative diagnostic studies have not been performed on the diagnostic value of serum hCG in women with PUL. Included studies showed substantial clinical heterogeneity in the definition of the outcome, and only data for the pregnancy outcome ectopic pregnancy (EP) were suitable for meta-analysis. The receiver operating characteristic curves showed that the serum hCG ratios and logistic regression models had a better performance as compared with an absolute single serum hCG level (as the curve was considerably closer to the diagonal, indicating no diagnostic value). Conclusions: Overall the study was limited by the high clinical heterogeneity of the data but in women with PUL diagnostic strategies using serum hCG ratios, either alone or in logistic regression models, have the best diagnostic performance in the case of EP. Well defined prospective comparative studies using standardized diagnostics and clinical application plus agreed definitions of outcome are required to identify the best strategy to diagnose pregnancy outcome in women with PUL.

Original languageEnglish
Article numberdms035
Pages (from-to)603-617
Number of pages15
JournalHuman Reproduction Update
Issue number6
Publication statusPublished - Nov 2012


  • Diagnostic
  • Ectopic pregnancy
  • hCG
  • Pregnancy of unknown location
  • Systematic review


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