Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary

Study question: Are there improvements in the accuracy of prediction of ectopic pregnancy (EP) in women with early symptomatic pregnancy using human chorionic gonadotrophin (hCG) curves when clinicians consider visits beyond the first 48 h after initial presentation?

Summary answer: Two hCG values, measured 48 h (2 days) apart, are often not sufficient to accurately predict the outcome of a woman with a pregnancy of unknown location (PUL), but adding a third visit on Day 4 or 7 significantly improved the prediction for 1 in 15 women.

What is known already: The use of serial hCG values is commonly used to aid in the prediction of the final diagnosis in women with a PUL. Initial outcome predictions based on two hCG values may often be incorrect.

Study design, size, duration: This retrospective multicenter cohort study included 646 women with a PUL, recruited over 2 years. Of these women, 146 were ultimately diagnosed with EP.

Participants/materials, setting, methods: Women presenting to the emergency room with first trimester pain or bleeding, with a PUL, at least 2 hCG values and a definitive final diagnosis from the University of Pennsylvania, University of Miami and University of Southern California, were recruited from 2007 to 2009.

Main results and the role of chance: Using currently recommended prediction rules, adding a third hCG evaluation on Day 4 after initial presentation significantly improved the accuracy of initial prediction from the first two values (48 h apart, or Day 2) by 9.3% (P = 0.015). Adding a third value on Day 7 improved prediction significantly by 6.7% (P = 0.031), compared with prediction based on first two values. The improvement in prediction by assessing four hCG values (Days 0, 2, 4 and 7) compared with three values (Days 0, 2 and 4) was 1.3% and not statistically significant.

Limitations, reasons for caution: Missing data imputation likely biased results toward the null; predicted outcomes may not match those made by clinicians; and the study does not predict intrauterine pregnancy and spontaneous miscarriage separately.

Wider implications of the findings: This study provides useful information for the prediction of outcomes for women with a symptomatic first trimester pregnancy of unknown location, but may not be generalizable to all pregnant women.

Study funding/competing interest(s): Supported by NIH grant numbers R01-HD036455 to Dr Barnhart and Dr Sammel, K24HD060687 to Dr Barnhart, and 5T32MH065218 to Ms. Zee. The authors have no conflicts of interest to declare.