Improvement of the Post ICSI Pregnancy Outcome by Induction of the Acrosome Reaction Prior to ICSI

1. Introduction Intracytoplasmic sperm microinjection (ICSI) produces 70% of fertilized oocytes and zygotes which mostly develop normally. To perform ICSI, a spermatozoon is taken from a sperm suspension after gradient migration. It is then immobilized by breaking its flagellum using a micropipette, and introduced into the oocyte cytoplasm.

The rate of spontaneous acrosome reaction in humans is less than 20 %. Two studies on the percentage of acrosome reacted and immobilized sperm showed that 95% of them have a destabilization of the membrane but only 17.8% of them had made a full RA. In other words, when we microinjected 10 spermatozoa, only 2 of them are completely rid of their acrosome material. All others are introduced into the oocyte with acrosomal material. But this material does not normally enter the oocyte since the acrosome reaction is a prerequisite to the passage of the zona pellucida that surrounds the egg .

The importance of using an acrosome-reacted spermatozoon for the success of ICSI has been previously highlighted in several animal species. It has been demonstrated that the induction of the acrosome reaction in mice lead to higher fertilization rates (from 30% to about 60 % ) . It is similar, in the rabbit and horses . Kimura et al. also reported that mouse oocytes injected with acrosome-intact rabbit and hamster sperm exhibited a nuclear activation and cessation of embryonic development without reaching the two-cell stage. This "cytotoxicity" of the same sperm disappears when they are released from their acrosomes before injection. In another study, the detrimental effect on oocyte survival of the presence of the acrosome during the injection of sperm heads was demonstrated in the golden hamster. All oocytes microinjected with acrosome-intact sperm were dead, while only those injected with acrosome reacted sperm have not only survived, but have also developed to the stage of two pronucleus in 79 % of cases and helped to get live births ( 19%).

The team of Yanagimachi reported a study on the potentially dangerous effect of the incorporation of the sperm acrosome of different species within mouse oocytes. According to these authors, harmful components would probably be the enzymes such as trypsin-like acrosine and hyaluronidase, since their injection mimicked the effects of ICSI with acrosome-intact sperm. In the same study, it was confirmed that the toxic effects were correlated with the size of the acrosome and therefore the contents of protease enzymes.

The toxic effects of the acrosome and its contents have been described explicitly by Morozumi and Yanagimachi. It induces deformation of the oocyte with an irregular appearance, edema or cytolysis with a pseudo-vacuolated cytoplasm appearance. Furthermore, it has been established that the damage caused by exogenous or acrosomales enzymes were correlated with oocyte cytoskeleton disruption through an aberrant accumulation of microtubules in the cortex of the oocyte.