The cumulus-corona-oocyte complex, composed of cumulus granulosa cells embedded in a matrix of hyaluronan oligosaccharide chains cross-linked by hyaluronan binding proteins and proteoglycans, surrounds each oocyte and must be removed prior to intracytoplasmic sperm injection (ICSI). This is traditionally achieved using enzymatic digestion of the matrix with a bovine-derived hyaluronidase followed by mechanical denudation through pipetting. A human recombinant hyaluronidase (Cumulase) has been developed with the intent of circumventing the problems and concerns associated with the animal origin and lack of purity of the bovine-derived form of the enzyme. In order to compare the effect of Cumulase with that of the bovine enzyme on the rates of normal fertilization and oocyte damage, a retrospective study using four experienced practitioners was performed. In 2006, using Cumulase, a significantly increased rate of normal fertilization (P = 0.0003) and a significantly decreased rate of oocyte damage (P < 0.0001) were observed compared with 2005, during which time bovine-derived hyaluronidase was predominantly used. This study indicates that Cumulase is safe and effective for use in the removal of the cumulus-corona-oocyte complex prior to ICSI, and may have several distinct advantages over the animal-derived form of the enzyme in terms of safety and efficacy.