Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic Sperm Injection (ICSI) is used to treat severe male infertility. Male infertility is a lowering of a male's sperm count or sperm quality sufficient to reduce a couple's chance of pregnancy. Male infertility is often classified as mild, moderate or severe based on the number of motile sperm and the number of normally shaped sperm in a man's semen. Men with fewer than five million sperm per mililiter of sample or fewer than 4 percent normally shaped sperm are classified as having severe male infertility.

During IVF, couples who do not have male infertility have the woman's eggs inseminated by a standard insemination procedure that involves placing a small volume of specially prepared motile sperm with the eggs in a dish. The cells surrounding the egg are called the cumulus and coronal cells. The head of a normal sperm contains enzymes that help the sperm break a small hole through the cumulus and coronal cells. Vigorous sperm motility is necessary for penetration of the cumulus and coronal cells. If the sperm does not have a normally shaped head, a normal amount of enzymes, or normal motility, it will not be able to reach the surface of the egg. After the sperm breaks its way through the cumulus and coronal cells, it must then bind to the outer coat of the egg called the zona pellucida. The sperm must possess normal receptors on its head to first bind to, and then break its way through the zona pellucida to reach the egg's membrane. When the sperm reaches the egg membrane, it must be capable of binding to the membrane to fertilize the egg. Normal sperm receptors are again required to complete this step in the fertilization process.

The process of fertilization as outlined above is complex and requires sperm to function normally. The sperm from men with male infertility often do not possess one or more of these normal sperm functions. Therefore, when sperm and eggs are simply placed together in a dish, as is done in the standard insemination procedure, the eggs often do not fertilize. When this happens, there are no embryos for transfer, and thus, no chance of pregnancy with IVF.

The ICSI technique was developed to assist the fertilization process in couples where the male has severe male infertility. The ICSI technique is a highly successful procedure that involves injecting one sperm directly into the egg using a microscope equipped with specialized micromanipulation equipment. The first step in ICSI involves selecting a healthy-appearing sperm for injection into the egg. The tail of the selected sperm is gently rubbed with a micropipette to immobilize it. This is necessary so the sperm does not continue to swim after it is placed inside the egg, which could damage the egg's delicate internal structures. After the sperm is immobilized, it is carefully drawn up into the micropipet with a very small amount of culture solution. The egg is carefully positioned on another pipet called a holding pipet to stabilize the egg. The small micropipette containing the sperm is then inserted into the egg. A small amount of the egg's internal material, called the cytoplasm, is then pulled up inside the micropipette with the sperm to ensure that the pipette is actually inside the egg. After confirming that the micropipette is inside the egg, the small amount of egg cytoplasm is expelled with the sperm and the micropipette is removed from the egg. The injected eggs are placed in an incubator for 16-18 hours, and then checked for signs of normal fertilization. Eggs that are normally fertilized will have one round female structure, called the female pronucleus, and one round male pronucleus in the center of the egg. These are the female and male chromosomes, which will come together a few hours later to form the early embryo.

The ICSI procedure can be used successfully to treat a wide array of male infertility disorders, such as low sperm counts, low sperm motility, or abnormally shaped sperm. ICSI may also be used to treat a condition called azoospermia, which is the complete absence of sperm in the man's ejaculate. When no sperm are present in the ejaculate, the sperm aspiration techniques, Percutaneous Sperm Aspiration (PESA) and Testiculare Sperm Extraction (TESE) may be used to obtain sperm from the male's reproductive tract. These sperm may then be used in conjunction with IVF and ICSI.

Even in cases of very severe male infertility, 60-70 percent of the eggs usually fertilize with the ICSI technique. These rates of fertilization are similar to those achieved with the standard insemination procedure in couples with normal male fertility. Clinical pregnancy rates and delivery rates are also similar for normal male fertility using the standard insemination procedure and for severe male infertility using the ICSI technique.

Because the ICSI procedure bypasses many steps in the normal fertilization process, babies born from the ICSI technique have been carefully studied for birth defects. Several large IVF programs, including the Belgium IVF program that originally developed the ICSI technique, have published studies showing that there is no increased risk of birth defects in babies born from the ICSI procedure. The Belgium IVF program reported the first successful ICSI pregnancy in 1992 and therefore, has several years of experience with this procedure. The Belgium program recently reported on the health of ICSI children 2 years of age and older. Again, no increased risk of birth defects or other health problems were found. The Mayflower ICSI program was initiated in 1994. No increase in birth defects or other abnormalities have been noted in the Mayflower ICSI program compared with couples having the woman's eggs inseminated by the standard insemination procedure. The miscarriage or pregnancy loss rate is also no higher for ICSI.

Although no general increase in birth defects or other health problems have been found in children born from ICSI, some of the sons born from ICSI will likely have the same infertility disorder as their father. This is because 5-15 percent of men with severe male infertility have a defect in their Y chromosome. This defect usually consists of one or more missing fertility genes on the Y chromosome. The missing infertility genes, called gene defects, will be passed on to male, but not female offspring, because only male offspring have a Y chromosome.

About 4 percent of men with severe male infertility have numeric or structural chromosomal abnormalities, such as chromosomal translocations or chromosomal inversions. In some cases these types of defects may result in an increased likelihood of pregnancy loss or birth defects. Couples may wish to discuss with their physician the possibility of being tested for Y-gene defects or chromosomal abnormalities before they undergo treatment with IVF and ICSI.

Congenital absence of the vas deferens (or CAVD) is a male condition where the vas deferens, a tubule that carries sperm to the outside of the body, is missing. Men with CAVD often have a defect in a gene associated with cystic fibrosis. If CAVD is diagnosed, it is important for the male to undergo testing for cystic fibrosis gene defects before proceeding with IVF. If a cystic fibrosis gene defect is found in the male partner, but not the female partner, then their son(s) will be at an increased risk for having the same CAVD infertility disorder as the male partner. If the cystic fibrosis gene defect is found in both partners, then genetic counseling is required because the couple's male and female offspring will be at high risk for inheriting the genetic disorder of cystic fibrosis.

See Male Infertility for more information.