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I have heard that the ART (artificial reproductive technology) procedure ICSI, where a sperm is injected directly into an egg, can result in genetic abnormalities in the resulting fetus. Can you tell me about them? How common are they?

-A curious adult from California

November 17, 2010

Yes, ICSI babies do have slightly more genetic problems than IVF or naturally conceived children. But it is unclear whether this is because of ICSI or the sperm used.

See, ICSI is used in special cases where couples are having a hard time getting pregnant. ICSI is often used when the man has genetic problems of his own and/or makes few or weak sperm cells. Each of these problems can increase the chances for a child with genetic problems. So it is hard to know whether it is the ICSI or the sperm used.

To explain where the problems might come from, here's some background. ICSI is a special form of IVF (in vitro fertilization). "In vitro" means that eggs are fertilized in a lab rather than in a womb. This is simply done by incubating an egg with lots of sperm.

One of the sperm cells then fertilizes the egg, which grows into an embryo. After a few days, one or more of the embryos are placed back in the mother's womb.

IVF was developed over 30 years ago and is now commonly used for couples who are having difficulty getting pregnant. Sometimes however, the man's sperm is not strong enough to fertilize the egg or a woman might have very few eggs. Then IVF won't work.

In those cases ICSI can be used. ICSI means "intracytoplasmic sperm injection". With ICSI, a single sperm is directly injected into an egg. This can lead to fertilization even in cases where normal IVF would not. ICSI has thus become a very popular technique.

But it is not a technique without some risks. Although studies disagree on the why, they all agree that ICSI babies are at a slightly higher risk for various genetic problems. What they can't figure out is whether the problem is the sperm or the technique.

Men who have to use ICSI to conceive often have infertility problems. These issues are often genetic ones. Something about their DNA may make their sperm weaker which may cause the increased risk for genetic problems.

Some possible technique problems have to do with a needle poking the egg and the lack of competition between sperm. Either or both may or may not increase the risk of genetic problems. Scientists just don't know yet if either of these is to blame. Or if it is something else.

What they do know is that the risk isn't very big. Almost certainly not big enough to dissuade someone from using ICSI to conceive. And there is even a way to decrease the risks of ICSI.

This can be done with PGS (preimplantation genetic screening). After a few eggs have been fertilized, one cell is taken from the embryo and screened for genetic problems. This way, the "healthiest embryos" can be chosen. However, PGS does not seem to increase the odds of a successful pregnancy.

The Small but Real Risks of ICSI

With ICSI, a lab worker chooses which sperm cell to use just by its looks. So unlike IVF or natural conception, there is no competition between sperm cells.

Competition is important because if a sperm has genetic defects, it is more likely to be weak. So having a competition is nature's way to select strong sperm with healthy DNA.

The lack of competition might be one reason why ICSI increases the odds for genetic problems. There have been many studies on this but they often disagree.

One area where something like this might cause a problem is issues with the sex chromosomes (X and Y). And ICSI children do seem to have more problems with these chromosomes.

With ICSI, sex chromosome defects occur in 1 of every 80-100 kids. The same problems happen in 1 of every 500 for IVF and normally conceived children. As you can see, there is an increased risk but the overall risk is still very small.

Another possible risk of ICSI is that the needle can damage the egg. A few eggs are lost because of this damage. But it is unclear whether the remaining eggs suffer from the needle or whether it increases the odds for genetic problems.

So, what are these genetic problems and what effects do they have? The most common problems are when cells are either missing some DNA or have too much of it. For example, infertile men are sometimes missing parts of their Y chromosome that are needed for making sperm. A child of this father conceived with ICSI can inherit this problem.

Also, genetic problems can cause "congenital malformations". This means a physical defect in the newborn baby.

Again, studies have conflicting results. But ICSI kids might have slightly more malformations than naturally conceived or IVF kids.

For example, a large study found that major malformations were found every 6 in 100 ICSI kids. This was slightly higher than found in children conceived with IVF (4 per 100) or normally conceived (2 per 100).

So, yes ICSI kids have a small increase in genetic problems. However, the vast majority of ICSI kids appear to be healthy and without genetic defects. Most people who use ICSI have no other means of getting children. For them, ICSI appears to be a good option with a relatively low risk.

Cool animation of ICSI.

By Dr. Hinco Gierman, Stanford University

Scientific publication on genetics screening of ICSI embryos IVF/ICSI with or without preimplantation genetic screening for aneuploidy in couples without genetic disorders: a systematic review and meta-analysis. Checa MA et al. Journal of Assisted Reproduction and Genetics. 2009 May;26(5):273-83. Review. [FREE TEXT]

Scientific publication on birth defects in ICSI children Congenital anomalies and other perinatal outcomes in ICSI vs. naturally conceived pregnancies: a comparative study. Al-Fifi S et al. Journal of Assisted Reproduction and Genetics. 2009 Jul;26(7):377-81. [FREE TEXT]

A single sperm (the white dot at the red arrow) is injected into an egg with a needle.

Some sperm just aren't hardy enough to fertilize an egg without help.
Electron micrograph of a sperm fertilizing an egg.