Intracytoplasmic Sperm Injection (ICSI) is used particularly when the quality of the sperm does not allow much hope for success with normal fertilization (for example, in the case of a low sperm count) or the couple has undergone normal IVF treatment, but the rate of fertilization has been poor regardless of an otherwise promising starting point. If necessary, sperm may be retrieved from epididymis or directly from the testicles for the intracytoplasmic sperm injection. In other words, very small numbers of sperm cells are enough for fertilization in the IVF + ICSI treatment. In some very rare cases no sperm is found, that in such cases donor semen can be used.

A very low sperm count may sometimes be linked to genetic reasons or chromosome changes. In such case sometimes the ultimate cause of infertility may be discovered with certain laboratory tests.