INDICATIONS FOR ICSI Although there is no "standard of care" in this field of medicine regarding which cases should have the ICSI procedure and which should not, it is the recommended and most effective method in couples with male factor infertility related to CF or the CF gene. Most infertility clinics are currently recommending in vitro fertilization (IVF) with ICSI for: 1. All couples with male factor infertility that do not want donor sperm insemination. 2. All couples with infertility with: Sperm concentrations of less than 15-20 million per milliliter (Men with CF who have CBAVD fall into this category) OR Sperm motility less than 35% (Men with CF who have utilized the MESA retrieval because of CBAVD fall into this category) OR Very poor sperm morphology (subjective - specific cutoff value not appropriate) 3. All couples having IVF who have had a previous cycle with no fertilization - or a low rate of fertilization (low percentage of mature eggs that are normally fertilized). 4. All couples having IVF who have a very low yield of eggs at the egg retrieval - our current cutoff is 5-6 (or less) eggs. In this scenario, ICSI is being used to try to get a higher percentage of eggs fertilized than with conventional insemination of the eggs (just mixing eggs and sperm together).

Please click on the following links for video files and news clips regarding the ICSI procedure. For video File, click here For the second video file, click here For news clip, click here

THE ICSI PROCEDURE 1. The mature egg is held with a specialized holding pipette. 2. A very delicate, sharp and hollow needle is used to immobilize and pick up a single sperm. 3. This needle is then carefully inserted through the zona (shell of egg) and in to the cytoplasm of the egg. 4. The sperm is injected in to the cytoplasm and the needle carefully removed. 5. The eggs are checked the next morning for evidence of normal fertilization. Fertilization rates for ICSI in most good IVF programs are about 60-85% of eggs injected. In some studies, the pregnancy rates for in vitro fertilization procedures with ICSI have been shown to be higher than that for IVF without ICSI. This is because in many of the cases needing ICSI, the female is relatively young and fertile (good egg quantity and quality) as compared to some of the women having IVF for reasons other than male factor infertility. Another way to say this is - average egg quantity and quality is usually better in ICSI male factor cases because it is less likely that there is a problem with the eggs.  As compared to cases with unexplained infertility where there is a higher probability of a somewhat reduced egg quantity and quality (on the average, since some women in this group have egg related issues). IVF with ICSI pregnancy rates vary according to the specifics of the individual case, the ICSI technique used, the skill of the individual performing the procedure, the overall quality of the laboratory, the quality of the eggs, and the embryo transfer skills of the physician performing that procedure. Sometimes ICSI is done for "egg factor" cases - low ovarian reserve situations. This is when there is either a low number of eggs, or lower "quality" eggs (or often both). In such cases, pregnancy rates are somewhat lower (as a group) since the main determinant of IVF success is the quality of the transferred embryos - and the quality of the eggs is a crucial determinant of the resulting embryo quality.  Most IVF treatments involving men with CF and CBAVD have higher success rates as the cause of infertility is known ad many of the women do not have egg quality or quantity problems. In some cases, assisted hatching might be done on the embryos prior to transfer, in order to maximize chances for pregnancy.

Figure 3: Fertilized egg demonstrating the two nuclei--one from the father, one from the mother.

Figure 1: Immobilizing the sperms tail before picking it up

Figure 2:  Injection of Sperm into the Egg

POSSIBLE RISKS 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. 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 OR cystic fibrosis diagnosis. These men can have obstructive azoospermia (no sperm in the ejaculate) because of a congenital bilateral absence of the vas deferens (a tube that carries sperm). These men are good candidates for sperm aspiration from the testicle (MESA) and then IVF with 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.

MORE RISKS 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. All of the studies done on babies born after ICSI are not in agreement - many show no increase in birth defects, or any kind of chromosomal abnormalities, but at least one study showed an increased incidence of sex chromosome abnormalities in children that were born as a result of ICSI. These abnormalities are not considered "major malformations". A published study from a group in Belgium (see the April 1998 issue of the journal "Human Reproduction" for 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 (possible) risk. However, this is a personal decision for each couple to make. 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)