External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study

E. Christodoulou, S. Bobdiwala, C. Kyriacou, J. Farren, N. Mitchell-Jones, F. Ayim, B. Chohan, O. Abughazza, B. Guruwadahyarhalli, M. Al-Memar, S. Guha, V. Vathanan, D. Gould, C. Stalder, L. Wynants, D. Timmerman, T. Bourne, B. Van Calster*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective To validate externally five approaches to predict ectopic pregnancy (EP) in pregnancies of unknown location (PUL): the M6P and M6NP risk models, the two-step triage strategy (2ST, which incorporates M6P), the M4 risk model, and beta human chorionic gonadotropin ratio cut-offs (BhCG-RC). Design Secondary analysis of a prospective cohort study. Setting Eight UK early pregnancy assessment units. Population Women presenting with a PUL and BhCG >25 IU/l. Methods Women were managed using the 2ST protocol: PUL were classified as low risk of EP if presenting progesterone = 5% was used to classify PUL as high risk. Missing values were imputed, and predictions for the five approaches were calculated post hoc. We meta-analysed centre-specific results. Main outcome measures Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. Results Of 2899 eligible women, the primary analysis excluded 297 (10%) women who were lost to follow up. The area under the ROC curve for EP was 0.89 (95% CI 0.86-0.91) for M6P, 0.88 (0.86-0.90) for 2ST, 0.86 (0.83-0.88) for M6NP and 0.82 (0.78-0.85) for M4. Sensitivities for EP were 96% (M6P), 94% (2ST), 92% (N6NP), 80% (M4) and 58% (BhCG-RC); false-positive rates were 35%, 33%, 39%, 24% and 13%. M6P and 2ST had the best clinical utility and good overall calibration, with modest variability between centres. Conclusions 2ST and M6P performed best for prediction and triage in PUL. Tweetable abstract The M6 model, as part of a two-step triage strategy, is the best approach to characterise and triage PULs.

Original languageEnglish
Pages (from-to)552-562
Number of pages11
JournalBjog-an International Journal of Obstetrics and Gynaecology
Issue number3
Early online date7 Oct 2020
Publication statusPublished - Feb 2021


  • Beta human chorionic gonadotrophin ratio
  • ectopic pregnancy
  • prediction model
  • prediction model validation
  • pregnancy of unknown location
  • progesterone
  • HCG


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