Evaluating cut-off levels for progesterone, beta human chorionic gonadotropin and beta human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study

Introduction There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and beta human chorionic gonadotropin (beta hCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, beta hCG, and beta hCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. Material and methods This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial beta hCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, beta hCG, and beta hCG ratio. Results Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for beta hCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had beta hCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single beta hCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the beta hCG ratio. Although the median beta hCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and beta hCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. Conclusions Cut-off levels for beta hCG, beta hCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although beta hCG ratio and progesterone have slightly better performance in comparison, single beta hCG used in this manner is highly unreliable.