The hCG discriminatory zone in ectopic pregnancy: does assay harmonization matter?

Ectopic_Pregnancy_DiagramEctopic pregnancy is a potentially life threatening complication of pregnancy. It occurs when the embryo implants outside the uterine cavity, most commonly in the fallopian tube. Common symptoms include nausea, abdominal pain, and slight vaginal bleeding. Approximately 2% of all pregnancies are ectopic pregnancies and they require emergency treatment to either prevent rupture of the fallopian tube or treat a woman with a ruptured ectopic pregnancy.

Diagnosis of an ectopic pregnancy requires the exclusion of a normal, intrauterine pregnancy. This is often facilitated by the use of transvaginal ultrasound (TVUS) to visualize the location of the yolk sac or embryo, which should be able to be seen by the end of the 6th week of gestation. However, such precise dating is often not available for patients that seek medical attention with symptoms of ectopic pregnancy and so hCG testing is often used as a surrogate marker for gestational age. The serum hCG result is interpreted against the “hCG discriminatory zone.” This is the hCG concentration that, once exceeded, means that the embyro should be large enough for TVUS to always detect it. However, it is inappropriate to diagnose a patient with an ectopic pregnancy even if no embryo is observed in the uterus when the hCG concentration has exceeded the discriminatory zone. 

The hCG discriminatory zone is commonly described as an hCG concentration between 1,500 and either 2,000, 2,500 or 3,000 IU/L. Guidelines from the American College of Obstetricians and Gynecologists define it as 1,500 to 2,000 IU/L.

The management of patients with a suspected ectopic pregnancy would be easier if hCG assays were harmonized, meaning that, regardless of the assay used to measure the hCG concentration, the results would be equivalent. In other words, it would be ideal if a sample tested for hCG on one manufacturer’s test platform was equivalent to the result obtained from another manufacturer’s test platform. Unfortunately, hCG assays are not harmonized, yet many clinicians are unaware of this limitation.

Along with colleagues, I recently published the results of a study that evaluted if the lack of hCG test harmonization would affect the interpretation of an hCG result with regards to the hCG discriminatory zone. The findings confirmed that there was, indeed, a lack of harmonization between 7 commonly used hCG assays. However, when we calculated what the expected hCG discriminatory zone should be for the different assays, all of them, with one exception, would have been within 9% of the frequently cited hCG discriminatory zone cutoffs of 1,500 to 3,500 IU/L. That amount of variation is very reasonable and is not cause for alarm. The single exception was an hCG assay for which a discriminatory zone of 2,000 to 4,900 IU/L would be estimated to be equivalent. We concluded that, despite significant differences in hCG concentrations across different hCG tests, an hCG result within a discriminatory zone of 1,500–3,500 IU/L could be used without regard to a specific assay for all but one commonly used hCG test.

Watch a short video of me explaining this study!

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