External validation of risk prediction model M4 in an Australian population: Rationalising the management of pregnancies of unknown location

BACKGROUND: The prediction model M4 can successfully classify pregnancy of unknown location (PUL) into a low- or high-risk group in developing ectopic pregnancy. M4 was validated in UK centres but in very few other countries outside UK. AIM: To validate the M4 model's ability to correctly classify PULs in a cohort of Australian women. MATERIALS AND METHODS: A retrospective analysis of women classified with PUL, attending a Sydney-based teaching hospital between 2006 and 2018. The reference standard was the final characterisation of PUL: failed PUL (FPUL) or intrauterine pregnancy (IUP; low risk) vs ectopic pregnancy (EP) or persistent PUL (PPUL; high risk). Each patient was entered into the M4 model calculator and an estimated risk of FPUL/IUP or EP/PPUL was recorded. Diagnostic accuracy of the M4 model was evaluated. RESULTS: Of 9077 consecutive women who underwent transvaginal sonography, 713 (7.9%) classified with a PUL. Six hundred and seventy-seven (95.0%) had complete study data and were included. Final outcomes were: 422 (62.3%) FPULs, 150 (22.2%) IUPs, 105 (15.5%) EPs and PPULs. The M4 model classified 455 (67.2%) as low-risk PULs of which 434 (95.4%) were FPULs/IUPs and 21 (4.6%) were EPs or PPULs. EPs/PPULs were correctly classified with sensitivity of 80.0% (95% CI 71.1-86.5%), specificity of 75.9% (95% CI 72.2-79.3%), positive predictive value of 37.8% (95% CI 33.8-42.1%) and negative predictive value of 95.3% (95% CI 93.1-96.9%). CONCLUSIONS: We have externally validated the prediction model M4. It classified 67.2% of PULs as low risk, of which 95.4% were later characterised as FPULs or IUPs while still classifying 80.0% of EPs as high risk.