In Vitro Pregnancy Screening

Screening for Down’s syndrome in IVF or in vitro pregnancies

Effect of IVF on hormone marker levels

Many women who seek fertility treatment are older and are therefore at greater risk for fetal chromosomal abnormalities. Consequently, many of these women will have 1st and 2nd trimester screening tests performed to try to identify abnormal fetuses. However, IVF treatment may cause these levels to differ from spontaneous pregnancies and therefore they should be interpreted with caution. In fact, one study has demonstrated that the rate of falsely abnormal results is twice as high in In vitro pregnancies.

Overview -- screening for chromosome abnormalities

Any test that is performed on a pregnant woman to find an abnormal fetus has a chance for making the correct diagnosis and a certain chance for making an incorrect diagnosis. One type of error could be the result of the test not finding an affected fetus. This is called a false negative. A test which is very good at finding an abnormality is said to have a high detection rate. The higher the detection rate of a test, the lower the false negative rate will be. A second type type of error can result if the test indicates that a normal fetus "abnormal". This is called a false positive.

Ideally, we would like to have a test with a high detection rate and a low false positive rate. However, in practice, it usually doesn’t work like that. In fact, the higher the detection rate of a test, the greater the chance for a false positive.

If the results of a screening test is determined to be abnormal, then confirmation of a fetal chromosome abnormality is accomplished by checking the chromosomes directly through an amniocentesis or chorionic villous sampling (CVS). These tests are more invasive and carry a small risk for fetal loss. Thus, keeping the false positive rate as low as possible as a highly desirable idea. This would reduce the number of times an amniocentesis or CVS had to be performed. In that way, there would hopefully be very few fetuses lost from performing the amniocentesis.

Second trimester screening tests

Hormone levels drawn from the blood a pregnant woman between the 15th and 20th week of pregnancy have been studied for their ability to predict a chromosomally abnormal pregnancy. Initially an association was found between low levels of maternal serum alpha-feto protein and fetal chromosomal abnormalities including Down's Syndrome. Subsequently, an association also found with elevated hCG levels, and decreased unconjugated estriol level. These three blood tests formed the basis of the "Triple Screen". More recently, a fourth hormone, Inhibin-A was found in higher levels in affected pregnancies.

Comparisons
Test Detection Rate False Positive Rate
Triple Test – Study A 77%
9% 
Triple Test – Study B 69%
 14%
Quadruple Test – Study A 83%
 6%
Quadruple Test – Study B 81%
 7%


This comparison tells us that using all four markers, raises the detection rate and lowers the chance for a false positive and thus is a better screening test than the triple screen.

First trimester screening tests

In the early 1990s, researchers discovered that measuring the thickness of the skin at the back of the neck of a fetus with ultrasound could predict fetal chromosomal abnormalities. Several years later, it was found that early in pregnancy, low levels of a hormone called pregnancy associated plasma protein A (PAPP-A) and high levels of hCG were associated with fetal chromosome abnormalities.

Comparisons

Detection Rate False Positive Rate
Study A 83% 6%
Study B 79% 9%
Study C 85% 5%


Studies looking at the effect of IVF on hormone marker levels

The data from study A (below) were obtained from analysis of 151 IVF pregnancies. This is considered a relatively small study. The data from study B was combined from multiple centers and included over 1500 pregnancies. This is considered a large study and the results would be considered to be more valid. Although the trends in Study B were similar to those seen in Study A, statistical analysis indicated that the results could have been due to chance. In fact, a third study did not find a difference in the markers between IVF pregnancies and spontaneous pregnancies.

Comparisons

Abnormal if.. Effect of IVF
Study A Study B
hCG Increased 9-14% higher 7% higher
Estriol Decreased 6% lower
12% lower
AFP Decreased No difference 6% lower

 

 

 

Last Updated ( Friday, 19 June 2009 )