Predicting Outcomes in Pregnancies of Unknown Location

Emma Kirk; Tom Bourne


Women's Health. 2008;4(5):491-499. 

In This Article

Serum hCG Levels

A single serum hCG measurement is used by some as a discriminatory level to help with the detection of ectopic pregnancy. The concept was initially developed with respect to transabdominal ultrasound examinations, when it was reported that the absence of an intrauterine gestational sac at an hCG concentration of greater than 6500international units (IU)/l had a sensitivity of 100%, a specificity of 96%, a positive predictive value of 86% and a negative predictive value of 100% for the prediction of an ectopic pregnancy. This approach was 98% efficient, based on a 19.4% prevalence of ectopic pregnancies among the group.[11] However, a high negative predictive value for diagnosing a clinical outcome with a high prevalence does not demonstrate that the test has a high diagnostic performance.

The introduction of high-resolution TVS has led to the discriminatory hCG level being decreased. Serum hCG levels of 1000, 1500 and 2000IU/l have been used.[12,13] However, a study on the use of varying discriminatory levels has demonstrated that using a single value of serum hCG in a PUL population is of limited value ( Table 1 ).[13] Many ectopic pregnancies in a PUL population have a relatively low serum hCG level, and so clinicians may be falsely reassured about the location of the pregnancy.

The change in serum hCG over time has been used to predict the outcome of PULs. Kadar etal. were the first to describe the minimal rate of increase for an IUP to be 66% over 2 days.[14] This study was based on a small sample of 20women and used an 85% confidence interval (CI). More recently, the minimal rise in serum hCG level in viable IUPs was reported to be 53%, on the basis of a 99% CI.[15] However, in clinical practice, a more conservative cutoff of 35% has been suggested to minimize the potential risk of terminating a wanted pregnancy.[16] Serum hCG curves for expected hCG declines in spontaneous miscarriages have also been described.[17] In addition, the change in serum hCG level over 48h has also been referred to as the 'hCG ratio' (hCG 48h:hCG 0h). An hCG ratio of less than 0.87 (or an hCG decrease >13%) has been demonstrated to have a sensitivity of 92.7% (95% CI:85.6-96.5) and a specificity of 96.7% (95% CI:90.0-99.1) for the prediction of a failing pregnancy.[18] There is less information on corresponding curves or rules for the behavior of serum hCG levels in ectopic pregnancies. Silva etal. recently concluded that there is no single way to characterize the pattern of serum hCG behavior in ectopic pregnancies.[19] They found that the number of women with an ectopic pregnancy who experienced an increase in hCG was approximately equal to the number who experienced a decrease. The hCG profile mimicked that of an IUP in 21% of women and that of a spontaneous miscarriage in 8% of women with an ectopic pregnancy.[19] Most investigators report a suboptimal rise in serum hCG in ectopic pregnancies, corresponding to a rise less than that expected in viable IUPs. A study investigating 196 ectopic pregnancies reported a sensitivity of 83% and a specificity of 95.4% for the detection of ectopic pregnancy, after initially excluding cases that were thought to be IUPs, defined by a serum hCG increase of more than 35% and failing pregnancies as a serum hCG decrease of more than 21-35%.[16] Of the 34 missed ectopic pregnancies in this study, 27 (80%) were misclassified as IUPs, as were 14% of all the ectopic pregnancies. Many of the difficulties in interpreting hCG levels in ectopic pregnancies are because up to 15-20% of them have doubling serum hCG times similar to that of IUPs.[19,20]


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