How do the M4 and M6 models perform in an Australian pregnancy of unknown location population?

Abstract

The diagnosis of a pregnancy of unknown location (PUL) is made when there is an elevated serum β human chorionic gonadotropin (βhCG) and no pregnancy on transabdominal and transvaginal ultrasound. Most of these pregnancies end as intra-uterine pregnancies or unsuccessful pregnancies and can be safely managed expectantly. However, up to 20% of these women will have an ectopic pregnancy. Several mathematical models, including the M4 and M6 protocols, have been developed using biochemical markers to triage PUL presentations. This rationalises numbers of tests and visits made without compromising safety and allowing timely intervention. We aimed to externally validate the M4 and M6 models in an Australian tertiary early pregnancy assessment service (EPAS). We performed a retrospective single-centre cohort study across fiveyears. Our study population included all women attending our EPAS with a PUL who had at least two serum βhCG levels and one progesterone level measured. The M4 and M6 models were retrospectively applied. Of the 360 women in the study population, there were 26 confirmed ectopic pregnancies (7.2%) and six persisting PULs (2%). The M4 model had a sensitivity and specificity of 72%. The M6P model had a sensitivity of 91% and specificity of 63%. The M6P misclassified two ectopic pregnancies into the low-risk group, compared with seven in the M4 model. The M6P model has the highest sensitivity of the three models and a negative predictive value of 99%. These numbers are comparable to the original United Kingdom population. Further prospective validation is planned.