Triaging pregnancies of unknown location: the performance of protocols based on single serum progesterone or repeated serum hCG levels

• Published in: Human reproduction (Oxford) 2014-05, Vol.29 (5), p.938-945
• Main Authors: Guha, S, Ayim, F, Ludlow, J, Sayasneh, A, Condous, G, Kirk, E, Stalder, C, Timmerman, D, Bourne, T, Van Calster, B
• Format: Article
• Language: English
• Subjects: Abortion, Spontaneous - blood; Abortion, Spontaneous - diagnosis; Adult; Chorionic Gonadotropin - blood; Clinical Protocols; Female; Humans; Pregnancy; Pregnancy, Ectopic - diagnosis; Progesterone - blood; Retrospective Studies; Triage; Young Adult
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deu045

How does a protocol based on a single serum progesterone measurement perform as a triage tool in women with pregnancy of unknown location (PUL) in comparison to protocols based on serial hCG measurement? Triage based on the logistic regression model M4 (using initial hCG and hCG ratio (48 h/0 h)) classifies the majority of PUL into low and high risk groups, in contrast to a progesterone protocol based on a serum level threshold of 10 nmol/l. Low progesterone has been shown to identify failing pregnancies and those at low risk of complications. A prediction model (M4) based on the initial hCG and the hCG ratio at 0 and 48 h can successfully classify PUL into low and high risk groups. A multi-centre diagnostic accuracy study of 1271 women was performed retrospectively on data from women at St. George's Hospital (SGH, London, UK) between February 2005 and 2006, Queen Charlottes & Chelsea Hospital (QCCH, London, UK) between April 2009 and August 2012, and the Royal Prince Alfred Hospital (RPAH, Sydney, Australia) between February 2008 and October 2011. The end-points were the final observed outcome for each pregnancy as a failed PUL (low risk), intrauterine pregnancy (IUP, low risk), or ectopic pregnancy (EP, high risk), and any interventions or complications for EP during the follow-up period. Complete data were available for initial progesterone, 0/48 h hCG and final outcome in 431 of 534 women (81%) at SGH, 396/585 (68%) at QCCH and 96/152 (63%) at RPAH. Missing values were handled using multiple imputation. Three diagnostic approaches were used to classify PUL as high risk: a range of serum progesterone levels were evaluated (>10, 16 and 20 nmol/l) for the progesterone protocol, risk of EP given by the M4 model ≥5% for the M4-based protocol, and hCG ratio was between 0.87 and 1.66 for hCG cut-offs as previously published. Results were analysed using random intercept models or stratified analysis to account for variability between centres. The progesterone protocol based on levels of >10 nmol/l classified 24% (95% confidence interval 20-28%) of failed PUL, 95% (92-97%) of IUP and 76% (67-83%) of EP as high risk. The M4 protocol classified 14% (11-17%) of failed PUL, 37% (31-43%) of IUP and 84% (76-90%) of EP as high risk. The hCG ratio cut-offs classified 10% (8-12%) of failed PUL, 15% (11-20%) of IUP and 63% (53-71%) of EP as high risk. Using complete cases only, 67% of EP treated with methotrexate (n = 48) and 89% surgically managed (n = 37) were correctl