Intracytoplasmic sperm injection (ICSI) is the most effective assisted reproductive procedure enabling fertilization in severe forms of male factor indications and male gamete dysfunction. Reliability of ICSI has allowed the expansion of its application to other forms of infertility rendering it the most popular assisted reproduction technology (ART) insemination method worldwide. The concern related to the invasiveness of ICSI together with the arbitrary selection of the inseminating spermatozoon has induced the execution of studies to compare the performance of ICSI in non-male factor infertility with standard in vitro insemination approach. Not surprisingly, the outcome has evidenced that ICSI does not yield higher pregnancy rates than in vitro fertilization but functions invariably as a normalizer of fertilization mollifying the absent or low fertilization. The follow-up studies on ICSI children have evidenced that the procedure is safe and the slightly higher incidences of neonatal malformations or de novo gonosomal abnormalities are related to the genetics of the infertile couples. Furthermore, ICSI is accepted for some specific indications such as low number and poor morphology oocytes, thicker zona, excess polyspermia, PGD/PGS/PGT (preimplantation genetic diagnosis/preimplantation genetic screening/preimplantation genetic testing), discordant HCV/HIV (hepatitis C virus/human immunodeficiency virus) couples, in vitro maturation (IVM), and oocyte cryopreservation. Only the advent of new biomarkers in combination with routine semen analysis capable of identifying the fertilization competence of the spermatozoon can guide the reproductive physician toward the proper insemination method.
