Problems of sperm fertility: a reproductive biologist's view

For natural fertilization to occur successfully, millions of spermatozoa must be deposited in the lower end of the female genital tract during mating. Considerably fewer spermatozoa are required for fertilization when spermatozoa are deposited in the upper region of the female tract. The extreme case of assisted fertilization is the direct injection of a single spermatozoon into an oocyte in vitro, which is referred to as intracytoplasmic sperm injection or ICSI. All that is required to fertilize an oocyte is a single spermatozoon with a genetically and epigenetically normal nucleus. Even spermatozoa with grossly misshapen heads and no motility at all are able to produce normal offspring by ICSI as long as their nuclei are normal. There is a distinct difference between natural and ICSI fertilization. In ICSI the sperm plasma membrane and the acrosome, which never enter the oocyte's cytoplasm during natural fertilization, are injected into an oocyte. There are reports that the oocytes injected with acrosome-less spermatozoa develop better than those injected with acrosome-intact spermatozoa. At least in the mouse, pre-spermatozoal cells (e.g., round spermatids) are able to produce fertile offspring by injection into oocytes. Whether 'spermatozoa' produced from embryonic stem (ES) or induced pluri-potent stem (iPS) cells are functional remains to be determined. Will assisted reproduction increase overall male infertility by spreading genes involved in infertility? This is most unlikely in view of the widespread propagation of spontaneous mutation in the general population. When assisted reproduction technologies are perfected, pregnancy through assisted reproduction will become as safe as pregnancy through natural conception.