Intracytoplasmic Sperm Injection (ICSI)

Intracytoplasmic sperm injection (ICSI) revolutionized treatment for male infertility. The procedure, introduced in 1992, involves taking single motile sperm and directly injecting the sperm into the egg to initiate the fertilization process. ICSI necessarily requires the in vitro fertilization (IVF) process to directly manipulate sperm and eggs.

ICSI boasts a fertilization rate of 50 to 80 percent, according to the American Society for Reproductive Medicine, but may be as high as 85 percent at some clinics. In 2007, about 33 percent of all ICSI cycles performed in the United States resulted in a live birth. Over 60 percent of all cycles using assisted reproductive technologies in the United States now involve ICSI.

Who can benefit from ICSI?

Most routine IVF procedures require at least 500,000 sperm per egg, says Paul Turek, MD, director of the male reproductive laboratory at the University of California at San Francisco. But many infertile men don't have that much, he adds.

That's why ICSI is often used when a man has a low sperm count or sperm with poor motility. When a man has a low sperm count because of a damaged or missing vas deferens, the pair of tubes that carries sperm from the testes to the penis, ICSI can be used to extract sperm. Men who have an irreversible vasectomy, and even men who were considered sterile after cancer treatment are prime candidates for ICSI.

"ICSI allows sperm that haven't been ejaculated to be used for fertilization," Turek says.

Many couples now choose the procedure simply because they believe it improves their chances for a successful IVF, especially when there are a limited number of a woman's eggs available.

How does ICSI work?

As in a routine IVF procedure, the woman must take fertility medications to stimulate her ovaries to produce multiple mature eggs. With a transvaginal ultrasound-guided needle, the eggs are removed from her ovaries and placed in a petri dish for fertilization. If a man's semen does not contain enough motile sperm, the doctor can extract sperm from a testicle with a needle. If a sperm sample reveals too few sperm, a biopsy can be taken from testicular tissue in hopes that there will be sperm attached. Similar to the egg retrieval procedure in women, this procedure can be quite painful, so it requires anesthesia.

Next, a single sperm is injected directly into each individual egg. The next day the eggs are checked to see if fertilization was successful. The fertilized eggs will remain in the petri dish for a few days as they continue to divide and become early embryos. Using a thin catheter, the doctor then places the embryos into the uterus.

The full IVF cycle takes about six weeks to complete -- from the first day of treatment until embryo transfer. In a third of ICSI pregnancies, more than one embryo implants, which can lead to a multiple pregnancy.

If there are extra embryos, they can be frozen for future fertilization attempts if the initial procedure is unsuccessful.

Risks and concerns

The processes of IVF and ICSI and other fertility procedures involve ovarian stimulation which can increase the risk of ovarian hyperstimulation syndrome, a potentially dangerous complication in which the ovaries become enlarged and, in severe cases, may lead to problems such as respiratory problems, blood clots, or kidney damage.

Although the medical research is not conclusive, in recent years a number of studies have shown that babies conceived through ICSI may have higher rates of certain birth defects and other problems. The risk of hypospadias -- a birth defect that causes the urethral opening to be located in the underside of the penis -- is higher in boys born through ICSI than in the general population. Also, because male infertility can be genetic, boys conceived through ICSI may inherit this condition and therefore have a higher chance of having fertility problems themselves as adults.

It has also been reported that ICSI babies have a four-fold increased risk of sex chromosome-linked genetic abnormalities that can result in various clinical syndromes.

A study of 5,138 Australian children showed that babies conceived through ICSI or IVF had twice as high of a risk of having a major birth defect as compared to babies that were conceived naturally. However, a study of 1,139 ICSI babies in Sweden showed that although ICSI babies had a slightly higher rate of minor or major birth defects, it was thought to be related to the higher rate of multiple and preterm births associated with fertility procedures, rather than to ICSI itself. Since there is not yet a consensus within the medical community, it's probably safest to assume that the use of ICSI or any other assisted reproductive technology may carry a small risk of birth defect.

As for whether the ICSI procedure affects children's learning skills, early research suggested that mental development may be slower among ICSI children. However, this study was small and has been refuted by several recent studies. Current research suggests that babies conceived through ICSI do not have a higher rate of learning disabilities. In 2005, the journal Pediatrics published a study of 1,423 five-year-old children from five European countries. The results showed that children conceived through ICSI or IVF did just as well as their naturally conceived peers on cognitive and motor development tests.

Some critics of the procedure argue that because it allows weaker sperm to fertilize eggs -- rather than relying on natural selection to favor the hardiest sperm it may lead to genetic defects. However, even with a slight increase, these genetic conditions remain rare: researchers have stated risks ranging from minor birth defects in 1.2 percent of ICSI children to 4.1 percent for major birth defects. Some believe that the higher incidence of birth defects and other issues may be because couples who use ICSI tend to be older and may have other health issues.

Cost

It costs about $10,000 to $12,000 for one cycle of ICSI, excluding medications and additional options such as sperm or embryo freezing. However, it may take more than one procedure to become pregnant. Costs also will depend on where you live. Many health insurers do not cover the cost of fertility procedures, but you may be able to discuss financing plans with your doctor.

Further Resources

American Society of Reproductive Medicine, http://www.asrm.org

American Fertility Association, http://www.theafa.org

RESOLVE, http://www.resolve.org

References

Interview with Paul J. Turek, MD, director of the male reproductive laboratory University of California at San Francisco Center for Reproductive Health

University of California at San Francisco. Intracytoplasmic Sperm Injection.

American Society for Reproductive Medicine. Intracytoplasmic Sperm Injection.

University of Pennsylvania. Intracytoplasmic Sperm Injection.

Advanced Fertility Center of Chicago. Intracytoplasmic Sperm Injection.

American Society for Reproductive Medicine. Assisted Reproductive Technologies A Guide for Patients. American Society for Reproductive Medicine.

Cornell Institute for Reproductive Medicine. What's New in Male Infertility Treatment at Cornell ICSI.

University of Pennsylvania. Male Infertility.

American Society for Reproductive Medicine. Cancer and Fertility Preservation.

American Urological Association. Management of Male Infertility.

The Cleveland Clinic. In Vitro Fertilization.

San Diego Fertility Center. IVF Example Calendar.

Gerris JM. Single embryo transfer and IVF/ICSI outcome: a balanced appraisal. Human Reproduction Update. 2005 11(2):105-121.

Ponjaert-Kristoffersen I, et al. Pediatrics. 2005 Mar;115(3):e283-9.

Hansen M,et al. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. New England Journal of Medicine. 2002 Mar 7;346(10):725-30.

Wennerholm UB, et al. Incidence of congenital malformations in children born after ICSI. Human Reproduction. 2000. 15(4):944-948.

Van Steirteghem A, et al. Follow-up of children born after ICSI. Human Reproduction Update. 2002 8(2):111-116.

Ovarian Hyperstimulation Syndrome Practice Guidelines. Fertility and Sterility. 2003 Nov;80(5):1309-14.

Bonduelle M, et al. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Human Reproduction. 2002. 17(10):2600-2614.