hCG measurements in pregnancies following in vitro fertilization (IVF)
A pregnancy test, in an IVF cycle, is generally scheduled approximately two weeks after an embryo transfer. This involves a blood test to measure the hormone of pregnancy – hCG (human chorionic gonadotropin). If positive (greater then 5 mIU/ml) the test is repeated two days later and it should rise appropriately. Initial studies had suggested that in naturally conceived pregnancies, the 2-day rise should be at least 66%. A slow rise was believed to be associated with an abnormal intrauterine pregnancy or a tubal pregnancy. More recent studies have shown that the rise could be as slow as 53% in 2 days and the pregnancy could still turn out to be normal.
What about IVF pregnancies? Do the same rules apply or should we use different criteria for these pregnancies? Dr. Beata E. Seeber (from Innsbruck Medical University, Innsbruck, Austria) discussed this very issue in a recent paper in the Journal “Fertility and Sterility”. The following are some of the important points presented in the paper.
- hCG levels determined 13-15 days after fertilization are higher in pregnancies from cleavage-stage day 3 embryos than those achieved through the transfer of blastocysts on day 5. Nonetheless, the percentage increase in serial measurement of HCG did not differ between these groups.
- A single hCG level cannot be used to differentiate between miscarriages and ectopic pregnancies.
- A combination of hCG levels on day 15 and 22 after embryo transfer can predict pregnancy outcome. When the hCG level on day 15 was >150 mIU/mL and an hCG day 22/hCG day 15 ratio of > 15 with a specificity of 94% and sensitivity of 47% for normal pregnancy. Conversely, when the hCG on day 15 was below 150 mIU/mL and the ratio of hCG on day 22/hCG on day 15 was below 15, there was an 84% chance of an abnormal pregnancy.
- There is no single hCG level that defines a normal pregnancy. The rate of increase in hCG levels, however, is important. The higher the percentage of rise in hCG drawn 2 days following the initial value, the better the live deliver rate.
- When compared to spontaneous pregnancies, the average doubling time of hCG level in IVF pregnancies appears to be the same (about 1.5 days.).
- In patients with ovarian hyperstimulation syndrome (OHSS), hCG levels should be interpreted carefully. These patients often have fluid that is shifting from the blood vessels to the abdominal cavity making the blood concentrated. When IV fluids are given, the blood levels can get diluted leading to variations in hCG levels. One can often see hCG levels that are flat or not rising normally in these patients only to show a normal rise when the OHSS is stabilized.
- What about twin and triplet pregnancies? These are more common with IVF and therefore deserve special discussion. The initial hCG levels are higher in multiple pregnancies than for singletons. But, the rate of rise is similar for both groups.
hCG levels are often used in combination with ultrasound to confirm the diagnosis of a normal vs. abnormal pregnancy. In very early pregnancy, the hCG levels are the primary diagnostic tool. In later pregnancy, ultrasound and clinical examination are often used in combination with hCG levels.