Interpretation of hCG in pregnancy is not an exact science

(Aotea News, September 2011)

By Max Reed, head of department, Biochemistry

Human chorionic gonadotrophin (hCG) can be used serially to monitor early pregnancy.

hCG is a glycoprotein with similar structure to FSH (Follicle Stimulating Hormone), LH (Lutenizing Hormone)and TSH (Thyroid Stimulating Hormone).

It appears in maternal circulation only after implantation has occurred, and this may range from eight days post-conception in approximately 5 per cent of patients to 11 days post-conception in more than 98 per cent of patients.

In pregnancy, hCG takes over from LH in promoting progesterone production by the corpus luteum, preventing menstrual bleeding.

Warning signs in early pregnancy

If the serum hCG concentration takes more than two days to double during early pregnancy, it could indicate a possible ectopic or a non-viable intrauterine pregnancy and gynaecological opinion should be sought.

Pregnancy staging (guideline only)

We have recently introduced the table below to our hCG listing in the Pathology Test Guide, and, as can be seen from the table, the expected values during pregnancy are very wide. This limits the use of single hCG concentrations as a marker of the stage of pregnancy.

High levels may be found in patients with twin or multiple pregnancies or with gestational trophoblastic disease. Low levels may be a marker of non-viable pregnancy; for example, ectopic pregnancy.

What the literature says -- algorithms have limitations

The serial use of hCG in monitoring pregnancy has been widely documented, with the aim of using hCG levels to differentiate failing or ectopic pregnancies from viable pregnancies.

Several algorithms have been developed to aid this process.

The majority of the algorithms rely on hCG doubling time or velocity, however, consensus on the actual doubling time of hCG remains elusive, for several reasons:

1. It is difficult to be precise about doubling time because different forms of hCG have different time courses and contribute in varying amounts to the doubling time,dependent on the gestational stage of the patient. The best estimates of doubling time are about two days.

Eventually the rate of rise slows and the peak hCG concentration is reached between eight and 12 weeks gestation. The concentration then falls to a plateau which persists over the second and third trimesters. After delivery or miscarriage hCG falls with a half life of one-to-two days, so may take up to six weeks to fall to non-pregnant levels.

2. Different assays detect the different forms of hCG with different levels of ensitivity and are calibrated against different reference materials.

At Aotea Pathology, we use the Roche E170 Electrochemiluminescence hCG + Beta immunoassay method. This method detects the holo-hormone, "nicked" forms, the ß-core fragment and the free ß subunit.

3. Different publications quote different doubling times as “normal”, with the trajectory of increase being described as exponential, log quadratic or quadratic, depending on the authors and cohort of patients studied.

4. A "normal" rise in hCG does not exclude ectopic pregnancy, and the rate of increase varies considerably between individuals. By the same token, there is not a single pattern for hCG in abnormal early pregnancy.