Treatment Overview

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology (ART) used to treat sperm-related infertility problems. ICSI is used to enhance the fertilization phase of in vitro fertilization (IVF) by injecting a single sperm into a mature egg. The fertilized egg is then placed in a woman's uterus or fallopian tube.

Sperm collection. If sperm cannot be collected by means of masturbation, they are surgically removed from a testicle through a small incision. This method of sperm retrieval is done when there is a blockage that prevents sperm from being ejaculated or when there is a problem with sperm development. To screen for possible genetic problems that could affect offspring, experts recommend that men with little or no sperm in their semen (not due to a blockage) have genetic testing before they proceed with ICSI.¹

Ovulation and egg retrieval. To prepare for an assisted reproductive procedure using your own eggs, you must get daily injections and be closely monitored for 2 weeks before egg retrieval. At home, you or your partner injects you with gonadotropin or follicle-stimulating hormone (FSH) to stimulate your ovaries to produce multiple eggs (superovulation). After the first week, your doctor checks your blood estrogen levels and uses ultrasound to see whether eggs are maturing in the follicles. During the second week, your dosage may change based on test results and ultrasound. If follicles fully develop, you are given a human chorionic gonadotropin (hCG) injection to stimulate the follicles to mature. The mature eggs are collected 34 to 36 hours later using laparoscopy or needle aspiration guided by ultrasound through the abdomen to the ovaries.

Sperm injection and transfer. Under high-power magnification, a glass tool (holding pipet) is used to hold an egg in place. A microscopic glass tube containing sperm (injection pipet) is used to penetrate and deposit one sperm into the egg. After culturing in the laboratory overnight, eggs are checked for evidence of fertilization. After incubation, the eggs that have been successfully fertilized (zygotes) or have had 3 to 5 days to further develop (zygotes or blastocysts) are selected. Two to four are placed in the uterus using a thin flexible tube (catheter) that is inserted through the cervix. The remaining embryos may be frozen (cryopreserved) for future attempts.

What To Expect After Treatment

Overall, in vitro fertilization (IVF)-related injections, monitoring, and procedures are emotionally and physically demanding of the woman. Superovulation with hormones requires regular blood tests, daily injections (some are quite painful), and frequent monitoring by your doctor.

These procedures are done on an outpatient basis and require only a short recovery time. Your doctor may advise you to avoid strenuous activities for the remainder of the day.

Why It Is Done

Intracytoplasmic sperm injection (ICSI) is used to treat severe male infertility, as when little or no sperm are ejaculated in the semen. Immature sperm collected from the testicles are usually unable to move about and are more likely to fertilize an egg through ICSI.

Some couples choose to try ICSI after repeat in vitro fertilization has been unsuccessful. In the United States, about half of IVF procedures are currently performed using ICSI technology.²

ICSI is also used for couples who are planning to have genetic testing of the embryo to check for certain genetic disorders. ICSI uses only one sperm for each egg, so there is no chance the genetic test can be contaminated by other sperm.

How Well It Works

Used with in vitro fertilization and eggs of good quality, ICSI often is a successful treatment for men with impaired or no sperm in the ejaculate. ICSI (using sperm collected from the testicles) produces an estimated 25% to 30% birth rate.³

ICSI does not improve the chances of conception for men with good-quality sperm in the ejaculate.⁴

Risks

Risks related to ICSI are the same as for in vitro fertilization, which increases the risks of ovarian hyperstimulation syndrome and multiple pregnancy.

• Superovulation with hormone treatment can cause severe ovarian hyperstimulation syndrome, occurring in 0.5% to 2% of all IVF treatment cycles.⁴ Your doctor can minimize the risk of ovarian hyperstimulation syndrome by closely monitoring your ovaries and hormone levels during treatment.
• Approximately 35% of births in the United States that result from assisted reproductive technologies such as IVF produce pregnancies with twins or more.⁵Multiple pregnancies are high-risk for both a mother and her fetuses.

Possible birth defect risks. ICSI is a relatively new ART procedure that has recently raised concerns about increased birth defect rates. While some studies have found no differences between ICSI and non-ICSI babies, a large, multicenter study has recently identified higher rates of certain birth defects in ICSI babies. In this study, newborns as well as fetuses that were not liveborn were examined. Overall, major problems that impact quality of life and need medical attention affected 8.6% of ICSI babies versus 6.9% of babies conceived naturally. The most common problems were heart and internal urinary/genital defects. Heart defects affected 2.1% of ICSI babies and 1.1% of non-ICSI babies. Internal urinary/genital defects affected 2.5% of ICSI and 1.6% of non-ICSI babies.⁶

Current research differs on whether ICSI-conceived children score lower on cognitive tests than other children. One study comparing naturally conceived and ICSI children between 1 and 2 years of age challenges earlier studies that found cause for concern. This study of over 500 children has found no differences in mental ability, nor in birth defects, between naturally conceived children and ICSI-conceived children.⁷ But larger and longer-term studies are necessary to prove that ICSI babies have no increased risks.

Treatment success versus the risk of multiple pregnancy

In order for a woman over age 35 to maximize her chances of conceiving with her own eggs and carrying a healthy pregnancy, she must have more embryos transferred than do younger women. This practice, though, increases her risk of conceiving multiple fetuses.

Because of the risks of multiple pregnancy to the babies, the American Society for Reproductive Medicine recommends that women under age 35 have no more than two embryos transferred, women age 35 to 37 have no more than three, women 38 to 40 have no more than four transferred, and women who have had repeated failed cycles or are over age 40 have no more than five embryos transferred.⁸

Women over 40 have a high rate of embryo loss when they use their own eggs. As an alternative, older women can choose to use more viable donor eggs.

What To Think About

Doctors advise men who have little or no sperm in their semen (not due to a blockage) to have genetic testing before ICSI.¹ Intracytoplasmic sperm injection is an effective treatment for sperm-related infertility, but it may carry genetic risks. Couples diagnosed with a chromosomal problem can seek genetic counseling to learn their potential for having a child with birth defects.

If you and your doctor are concerned about passing on a genetic disorder to your child, talk to your doctor about preimplantation genetic diagnosis. Some genetic disorders can be identified with specialized testing before an embryo is transferred.

Frozen IVF embryos that are thawed and transferred to the uterus are less likely to result in a live birth (29% success) than are newly fertilized IVF embryos (50% success).² But frozen embryos are less expensive and less invasive for a woman, because superovulation and egg retrieval aren't necessary.

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References

Citations

1. American Urological Association and American Society of Reproductive Medicine (2006). Report on the Evaluation of the Azoospermic Male. Fertility and Sterility, 86(Suppl 4): S210–S215.
2. Centers for Disease Control and Prevention (2006). Assisted Reproductive Technology (ART) Report: 2005 Preliminary Clinic Data by State and National Summary. Available online: http://apps.nccd.cdc.gov/ART2005/clinics05.asp.
3. American Society for Reproductive Medicine Practice Committee (2006). Report on Management of Obstructive Azoospermia. Fertility and Sterility, 86(Suppl 4): S259–S263.
4. Al-Inany H (2005). Female infertility, search date April 2004. Online version of BMJ Clinical Evidence. Also available online: http://www.clinicalevidence.com.
5. Speroff L, Fritz MA (2005). Assisted reproductive technologies. In Clinical Gynecologic Endocrinology and Infertility, 7th ed., pp. 1216–1274. Philadelphia: Lippincott Williams and Wilkins.
6. Ludwig M, Katalinic A (2002). Malformation rate in fetuses and children conceived after ICSI: Results of a prospective cohort study. Reproductive Biomedicine Online, 5(2): 171–178.
7. Sutcliffe AG, et al. (2003). A retrospective case control study of developmental and other outcomes in a cohort of Australian children conceived by intracytoplasmic sperm injection compared with a similar group in the United Kingdom. Fertility and Sterility, 79(3): 512–516.
8. American Society for Reproductive Medicine (2006). Guidelines on number of embryos transferred. Fertility and Sterility, 86(4): S51–S52.