Intracytoplasmic sperm injection, or ICSI, is a form of micro-assisted fertilization.

IVF without ICSI involves mixing thousands of motile sperm with each egg in a Petri dish in the lab (we call this insemination of the eggs). The sperm and eggs must then interact through biochemistry. The hoped-for result is fertilization of most of the eggs. However, in some cases, either egg or sperm factors are deficient and very few (or none) of the eggs become fertilized after overnight incubation with sperm.

ICSI involves selecting a sperm, picking it up with a specialized micro-needle and injecting it into the middle of the egg. It is somewhat similar to an arranged marriage. We are trying to force fertilization for each egg - instead of mixing sperm and eggs together and hoping that they all do well on their “overnight date”.

 ICSI is a very effective procedure to assist fertilization for couples with sperm problems, and has been in widespread use around the world since the early 1990’s. According to the 2002 National Summary Report on IVF published by the Center for Disease Control (CDC), over 95,000 IVF cycles using fresh eggs were performed in the US in 2002. Over half of these cases (53%) used ICSI.

Potential transmission of genetic disease

Male infertility is known to be associated (in some cases) with chromosomal and other genetic anomalies. There is known to be an increase in gross chromosomal abnormalities such as balanced translocations in men with very low sperm counts. Also, about 5% of men with very low sperm counts have small areas of missing DNA on their Y chromosome. This is referred to as a "Y micro-deletion". The technology to test for Y micro-deletions is now available.

Chromosomal testing (karyotype) of the male can also be done, to evaluate the normality of the male’s chromosomes. If you are interested in having any of this testing performed, be sure to ask about it before the female partner begins medications for treatment –results may not be available for several weeks.

There are some other specific genetic disorders that have been identified as causes of defective sperm production and male infertility. It is certain that there will be additional hidden or recessive genetic disorders that will be discovered in the future that are the cause of some other cases of male factor infertility. Techniques such as ICSI will, in some cases, lead to transmission of genetic problems that might cause infertility in male offspring, or could possibly be associated with other (at this time unknown) medical problems in the child. In some cases, these disorders probably would not be transmitted without ICSI - particularly if the couple remains childless.

There have now been many thousands of babies born after IVF with ICSI with follow-up after birth. Thus far, there has not been demonstrated to be any clear increased risk for birth defects. Most studies thus far have shown that the risk of birth defects after ICSI is the same as for babies conceived through IVF without ICSI, and for those conceived “naturally”. However, some studies have suggested that having IVF with ICSI might increase the risk for birth defects.

This is potentially confusing because the medical literature does not give a definitive answer. Some examples of studies from the literature on outcomes for babies after IVF with ICSI are presented here to illustrate:

One study did follow up on 1,987 children born after ICSI and showed that 2.3% had major malformations, which is comparable to figures known for children born after in vitro fertilization (IVF) without ICSI, or after natural conception. About 1 to 4% of children in the general population are born with a major malformation.

A different study showed an increase in sex chromosome abnormalities in children born from IVF with ICSI. These abnormalities are not considered "major malformations". This particular study showed that of 1082 prenatal tests on ICSI pregnancies, 0.83% (1 per 120 pregnancies) had sex chromosome abnormalities following ICSI, whereas the background risk in the population is about 0.2% (1 per 500 pregnancies). One possible explanation for this increase (if it is real) is that it could possibly be related to the nature of the sperm defect itself in some men with severe sperm abnormalities. In this study, all of these sex chromosome abnormalities were from cases with sperm from men with severe sperm defects. Other studies have not seen any increase in sex chromosome abnormalities after ICSI.

The studies done on babies born after ICSI are not in agreement - many show no increase in birth defects, while other studies have found some increase in the percentage of babies with birth defects. Certainly, more and larger studies will be done to clarify the issue of whether ICSI causes any kind of problem for the child. In the meantime, we continue with ICSI treatment for those couples willing to proceed after being informed of possible risks and benefits.

Although there is not yet any clear proof that ICSI causes any increase in problems in the resulting children, perhaps the safest assumption is that there is a small increase in the risk of birth defects for children born after IVF with ICSI. This increase (if it exists) might also be present for children conceived through IVF without ICSI as well.

Alternative treatment options to IVF with ICSI are:

1. Intrauterine inseminations with the male partner’s sperm. This involves sperm processing in the lab, and then placement of the processed sperm through the cervix and up into the uterine cavity using a sterile catheter.

2. Insemination of the female partner with donor sperm - or IVF with donor sperm if there is a female indication for IVF.

3. IVF without ICSI - which has a risk for total failure of fertilization that varies depending on both egg and sperm factors.

If you are considering IVF with ICSI and you have questions regarding these issues, it is important that you discuss the issues with us prior to signing the consent form and having ICSI performed on your eggs.