Managing Pregnancies of Unknown Location With the M4 Prediction Model or the NICE Algorithm: A Randomised Controlled Trial With Cross-Sectional Diagnostic Accuracy Data.

Objective: To determine the diagnostic performance and clinical utility of the M4 prediction model and the NICE algorithm managing women with pregnancy of unknown location (PUL).

Design: The study has a superiority design regarding specificity for non-ectopic pregnancy for M4, given that the primary outcome of sensitivity for ectopic pregnancy (EP) is non-inferior in comparison with the NICE algorithm.

Setting: Emergency gynaecology units in Sweden.

Population: 595 women with PUL.

Methods: Participants were randomised (1:1) to M4 or the NICE algorithm after two serum human chorionic (hCG) levels and were categorised as high or low risk of having an EP. The diagnostic performance was evaluated on cross-sectional data and utility by parallel groups.

Main Outcome Measures: The proportion of EP categorised as high risk (sensitivity) and non-ectopic pregnancies categorised as low risk (specificity). Clinical outcomes were assessed.

Results: The sensitivity for EP was 79% (115 of 146) for M4 versus 85% (124 of 146) for the NICE algorithm, p = 0.1496 and the specificity for non-ectopic pregnancies was 67% (300 of 449) for M4 and 74% (334 of 449) for the NICE algorithm, p = 0.0003. Clinical outcomes were similar between groups.

Conclusions: The sensitivity for EP by M4 was non-inferior to NICE, but specificity was better for the NICE algorithm. No between group differences were observed for clinical outcomes.

Trial Registration: NCT03461835, https://www.

Clinicaltrials: gov.