This is the second in a series of 10 responses to common questions/concerns about IVF treatment.


Concern #2: Will my baby be normal?

One of the biggest concerns facing any pregnant woman is whether or not her baby will be “normal.” When it comes to IVF, that concern looms even greater because of the fear that the introduction of an “unnatural” component into the equation might increase the likelihood of an abnormal offspring. There have been several publications in the literature that have shown an increased risk of developmental abnormalities in IVF babies. Such reports have only served to heighten this concern. Some of these reports have suggested that because of an increased risk of chromosomal abnormalities in miscarriage specimens resulting from pregnancy loss with IVF and because of an increased incidence in chromosomal defects such as Down’s syndrome (trisomy 21), Edward’s syndrome (trisomy 18) and Turner’s syndrome (XO monosomy), known to occur in IVF, there must clearly be a cause and effect relationship.

However, a careful review of the growing IVF experience suggests that most of the above mentioned developmental defects are attributable to the fact that the average age of women having babies through IVF is significantly higher than the comparable fertile population at large, and there is an established link between advancing age and chromosomal abnormalities. As an example, at the age of 30 years the chances of a woman giving birth to a baby with Down’s syndrome is about 1 in 1000 whereas at 40 the risk is about 1 in 150 and at 45 it is 1 in 35. It is “wear and tear” over time of eggs that have been in the mother’s ovaries ever since she was developing inside her own mother that is associated with an escalating risk of such chromosomal developmental abnormalities….whether the baby is born from spontaneous conception or IVF.

When it comes to non-chromosomal developmental abnormalities, it is possible that certain birth defects are indeed more common in the offspring of women undergoing IVF. Certain central nervous system disorders are increased in incidence in IVF babies but increase is slight.

It is true that chromosomal deletions leading to early pregnancy loss are more common in couples with male infertility. It is also a fact that infertile men undergoing IVF are more likely to have male offspring that manifest male infertility later in life. This is because some of the genes responsible for male infertility can by found on the Y chromosome and are therefore passed genetically to the male offspring.

Some concern has been expressed about the possibility that Intracytoplasmic Sperm Injection (ICSI), a procedure used to induce successful fertilization (primarily in cases of male infertility) might increase the risk of developmental defects. If this is the case, then it is not the procedure of ICSI itself that is at fault, rather it is the male infertility for which ICSI is performed. In fact, when ICSI is performed using normal male sperm there is no reported increase in the incidence of developmental defects, thereby proving that the procedure itself is safe. In addition, without ICSI, the chance of successful IVF in cases of male infertility would otherwise be very low. So the only option for male infertility outside of ICSI is the use of donor sperm. Most couples will opt for ICSI using the partner’s sperm given these options, even with the slight chance of passing the condition on to their male offspring.

Because of the above, it is important for all women undergoing IVF to submit to careful evaluation in the first and early second trimester. At the very least, this should include a high level ultrasound examination. For women over 35 years of age, ultrasound and blood screening as well as chorionic villus sampling (in the first trimester) or amniocentesis (in the second trimester) is indicated to exclude chromosomal abnormalities. There are certain highly specialized centers where genetic testing of amniotic fluid using polymerase chain reaction (PCR) can be done. It all depends upon the identification of the involved DNA sequences.

Genetic defects can also occur more frequently in couples of certain ethnic and regional groups. For example, Ashkenazi’s Jews, are at an inordinate risk of genetically transmittable diseases (e.g. lipoidoses such as Tay Sach’s Disease, Neiman Pick’s Disease, etc.). Sickle cell disease/trait is more common in patients of African extraction and Thalassemia is more prevalent in individuals of Mediterranean extraction. Thus, a careful directed pre-IVF genetic assessment should be done in such cases. The same applies in situations where cystic fibrosis is more likely to occur in the offspring (i.e., where there is a family history or the male has congenital blockage of the sperm ducts). Here again, pre-IVF genetic testing is essential. There are a whole host of additional genetically transmitted conditions and chromosomal balanced translocations where pre-IVF testing is likewise important.

Modern day access to chromosomal and genetic tests that can be performed on early embryos can minimize the risk of identifiable chromosomal and genetic abnormalities that can result in developmental defects. Tests such as Fluorescence In Situ Hybridization (FISH), Comparative Genomic Hybridization (CGH) and Polymerase Chain Reaction (PCR) can be performed on pre-implantation embryos. It should be borne in mind however that such tests are not infallible. In fact, there is about a 5% diagnostic error rate. Accordingly, any pregnancy resulting after such pre-implantation genetic tests that suggest a normal pregnancy should be followed up with through more detailed prenatal testing including but not limited to ultrasounds, blood tests and CVS/amniocentesis.

Conclusion: The risk of birth defects in the general population is 1-3% of all births. And, indeed, babies born from in vitro fertilization may also have birth defects. There are, however, a number of confounding factors that may lead to overstating the risk associated with the IVF process itself. First, birth defects occur more frequently in cases of multiple births and the incidence of multiple births is much higher with IVF, largely due to the purposeful transfer of multiple embryos, rather than being due to the technology itself. Second, the incidence of birth defects increases with advancing maternal age, and on average, women who conceive through IVF tend to be older than women who conceive naturally. Third, and perhaps most important of all, is the fact that couples who have infertility seem to have a higher rate of birth defects than the general population even if no fertility treatments are used. It follows that studies which use birth defect rates from the general population as a comparison to IVF, probably overestimate the risk from IVF.

Bottom line: while beneficial and highly effective, IVF (as with other medical technologies), is not devoid of risk. Thus, all patients considering treatment must be thoroughly, diligently and empathetically counseled so that a decision to proceed is at all times a fully informed one.

A multi-center study funded by the National Institutes of Health was performed
in 2005. 36,000 pregnancies were analyzed. 95% were spontaneously conceived,
1222 (3.4%) conceived with ovulation inducing drugs and 554 (1.5%) used IVF.
This study found no association between either fertility treatment and the
incidence of birth defects.