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  » Infertility  »  Pelvic scarring, pelvic and tubal adhesions and pelvic factor infertility

Part 1
General Considerations
Background

Intracytoplasmic sperm injection (ICSI) has developed as a form of micro-assisted fertilization. It is a remarkably effective procedure to assist fertilization for men with severe infertility. However, it bypasses all natural sperm selection processes that have evolved to regulate fertilization, and the long-term implications for the health and fertility of the children are unknown.

Technological "solutions" to male infertility are developing much more rapidly than is our understanding of the underlying causes. Primary testicular disease, for example, is the major diagnosis of infertility in about half the men that present at infertility clinics, but in most other cases the cause is unknown. Many of these cases are probably due to a genetic problem that results in abnormal sperm production. In such cases ICSI may offer the only hope of parenting. However, in many cases we are likely to be assisting the transmission of a genetic defect that will also cause reproductive dysfunction in the male offspring and possibly in future generations as well.

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, up to 13% of men with very low sperm counts have small areas of missing DNA on their Y chromosome. This is referred to as a "Y deletion". Currently, the technology to test for these deletions is not commercially available and reliable. Eventually, reliable and cost-effective tests for these deletions will be available.

One of the genetic defects associated with male infertility is associated with Cystic Fibrosis carrier status. These men can have obstructive azoospermia (no sperm in the ejaculate) through congenital absence of the vas deferens (a tube that carries sperm). They are good candidates for sperm aspiration from the testicle and ICSI.

Genetic testing is available on the male to evaluate whether he is a carrier for any of the known cystic fibrosis mutations. Chromosomal testing (karyotype) can also be done, to evaluate the normality of the male’s chromosomes. If you are interested in having any of this testing on the male, be sure to ask about it before the female partner begins any medications for the cycle – the results are not available for up to several weeks.

There are some other genetic disorders that have been identified as a cause 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 be associated with other (at this time unknown) disorders. In some cases, these disorders probably would not be transmitted without ICSI (particularly if the couple remains childless). We must accept this if we are willing to utilize the technique.

Risks to the child from intracytoplasmic sperm injection (ICSI)
Part 2
Sex chromosome abnormalities

There have now been thousands of babies born following ICSI with follow-up after birth.

As of yet, there has not been demonstrated to be any increase in birth defects. In a follow up study done on 1,987 children born after ICSI, 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.

The most current information indicates that there may be a slight increase in the incidence of sex chromosome abnormalities in children that were born as a result of ICSI. These abnormalities are not considered "major malformations".

A recent published study from a group in Belgium (see the April 1998 issue of the journal "Human Reproduction" for more details) 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).

Thus far, the only explanation for this increase is that it might somehow 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 found after sperm was used from men with severe sperm defects.

These types of sex chromosome abnormalities are not evident at birth and usually would not be noticeable until the child goes through puberty. At puberty the child may have abnormal development - particularly underdevelopment of sexual organs (penis and/or testicles in boys, vulva, ovaries and/or breasts in girls). The children with these sex chromosome abnormalities would also be likely to be infertile when they grow up.

Because the incidence of these sex chromosome abnormalities following ICSI is very low and since there is not an issue related to abnormal mental development or obvious birth defects in the children, the large majority of couples considering ICSI have decided to proceed with the procedure and accept this small risk. However, this is a personal decision for the couple to make - not for the physician.

The issue of chromosomal problems in children born after ICSI is further complicated by other follow-up studies that have shown no increase in risk for any type of chromosome abnormality. Certainly, more and larger studies will be done to clarify the issue - but this takes time. In the meantime, we continue with ICSI treatment for those couples willing to proceed after being informed of possible risks and benefits.

Alternative treatment options to IVF with ICSI are:

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

Insemination of the female partner with donor sperm (or IVF with donor sperm if there is a female indication for IVF)

If you undergo ICSI in our facility 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 the ICSI procedure performed on your eggs.