In 1992, the injection of a single sperm into a mature egg was performed for the first time. This revolutionary technique, called intracytoplasmic sperm injection (ICSI), gave men with extremely low numbers of motile sperm another option in addition to the use of donor sperm. For the first time, they could father their own biological children. ICSI is used in the following cases:

• Severe male factor infertility as indicated by a low sperm count
• A large number of abnormal sperm
• Low or absent sperm motility
• Problems with sperm binding to the egg or antisperm antibodies on the sperm surface that can interfere with the fertilization process

Since only very few sperm cells are needed for ICSI, it is possible to use epididymal or even testicular sperm for fertilization of eggs, if ejaculated semen is not available. Sperm cells from any of these sources can be cryopreserved (frozen) for use in a future treatment cycle. As the use of ICSI became standard clinical practice, the indications for ICSI increased and now can include previous failed fertilization (for any reason) and egg factors such as defects which allow more than one sperm to enter the egg, resulting in a genetic defect

Ongoing studies tracking the health of children produced using ICSI have to date been reassuring.

Men who are severely oligo- (low sperm) or azoospermic (no sperm in the ejaculate) are more likely to carry chromosomal abnormalities in their germ cells that are now more readily transmitted to their offspring because ICSI is available and they can reproduce. For this reason, it is recommended by the American Society for Reproduction that couples that are known to carry genetic abnormalities receive genetic counseling prior to choosing ICSI as a treatment option. Prenatal testing (amniocentesis or chorionic villus sampling) is also recommended when the couple has genetic abnormalities (e.g., abnormal karyotypes, Y microdeletions, CF mutations). Depending on the genetic disorder, it may be prudent to use preimplantation genetic diagnosis prior to embryo transfer to detect embryonic genetic abnormalities.

The ICSI procedure involves the same ovarian stimulation and egg retrieval as standard in vitro fertilization (IVF). A mature egg is selected, and the semen sample is processed to optimize the sample in terms of sperm motility and viability. The processed sperm are immobilized and then injected into the cytoplasm of the egg. At this point, the egg must respond to the sperm and the genetic material from the sperm and egg must commingle via a process called syngamy to produce a genetically unique fertilized egg. Because other steps in the fertilization process occur after entry of the sperm into the egg, ICSI is not always successful if other egg or sperm defects are present.