Human recombinant hyaluronidase (Cumulase®) improves intracytoplasmic sperm injection survival and fertilization rates

Abstract

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.

Percutaneous epididymal sperm aspiration and short time insemination in the treatment of men with obstructive azoospermia

“…Animal-derived products have limited purity and accidental transmission of pathogens cannot be excluded fully. These limitations inevitably imply an increased need for mechanical dispersal of the cumulus and corona by means of multiple pipetting, which could be harmful to the oocyte [27]. Evison and De Vos reported that the use of human recombinant hyaluronidase could improve ICSI survival and good embryo development compared with bovine hyaluronidase [27, 28].…”

Use of Hyaluronidase for Pharmacokinetic Increase in Bioavailability of Intracutaneously Applied Substances

“…Here, the enzyme detaches cumulus cells from the ovum in the process of denudation, where enzymes break down the ECM consisting of HA; rHuPH20 is increasingly used here as well. Studies show higher fertilisation rates as well as a reduction of oocyte damage when rHuPH20 is used compared to bovine HAase [91]. Recent articles deal with the use of HAase to enhance drug delivery in subcutaneously applied therapeutic agents.…”

Toxicity of the recombinant human hyaluronidase ALT-BC4 on embryonic development

“…Oocytes are traditionally denuded using bovine testis-derived hyaluronidase that affects the quality of oocytes and embryos [5]. In hospitals, human recombinant hyaluronidase was commercially used as an alternative to bovine-derived hyaluronidase owing to its purity, safety, and effectiveness.…”

“…Ishizuka et al have shown that prolonged treatment with hyaluronidase decreases the quality of mouse oocytes and that a shorter exposure time increases fertilization and developmental ability [9]. Furthermore, human oocytes treated with hyaluronidase have also been shown to have decreased oocyte survival, fertilization rates, and developmental ability following ICSI [4,5,10]. In pigs, the effect of different denuding procedures on oocyte damage and embryo development has previously been investigated [11].…”