Understanding HCG
HCG tests were first developed in 1968. Since then they have been widely accepted as an absolute, a fool proof test, when in reality they are not. There are always exceptions to the rules of nature and this is one of them. HCG is not just a single molecule. It actually has a couple different parts and many different variations of those parts. To put it simply, we will call those parts HCG-a, HCG-b, and HCG-beta core fragment. HCG-a closely resembles the luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone. HCG-b, however, is unique to pregnancy with the exception of certain HCG producing tumors.
Here is how it works in a nutshell. HCG-a “sandwiches” with HCG-b and forms what is known as intact HCG. That is what all urine and blood tests will test for.
Intact HCG is usually the most prominent form of HCG found in early pregnancy. However, by around 5 weeks in pregnancy, the most prominent form of HCG is HCG-beta core fragment (HCG-bcf). HCG-bcf is not recognized by most urine tests. When levels of HCG-bcf become very high, they can overwhelm the urine test in what is known as a “variant hook effect”.
In 2014 the variant hook effect was brought to the attention of the companies producing urine pregnancy tests, but only one over the counter brand changed their design. First Response Early Response is the only over the counter brand that can detect HCG-bcf. Because most urine tests don’t test for the variant HCG-bcf, there is a problem with tests appearing negative when the woman is actually pregnant and producing HCG.
Another form of the hook effect that can happen is when there is so much intact HCG being produced that it overwhelms the urine test. This is usually only seen when intact HCG levels rise to around 1,000,000 mIU/mL , which can also indicate gestational trophoblastic disease, molar pregnancy, or multiple fetuses.
One way to overcome the hook effect is to dilute the urine sample with water before testing.