ISCI, which has been developed over the past decade, is used in cases where a severe male factor of infertility is present. Candidates for ICSI may include patients with severe reductions in sperm number of motility, regardless of cause, and patients with a history of fertilization failure in conventional IVF. ICSI may also be used to achieve fertilization using aspirated sperm from patients with anatomic or surgical conditions (such as vasectomy) that prevent sperm from ejaculating.

ICSI attempts to achieve fertilization by the direct injection of a single sperm into the cytoplasm (interior) of the egg. Mature eggs are freed of the surrounding cells by a combination of enzyme treatment and microdissection. Using micromanipulation, the eggs are individually injected with a single sperm. Injected eggs are returned to the incubator and cultured until the transfer.