Genetic incompatibility of the reproductive partners: an evolutionary perspective on infertility

In natural fertilisation, the female reproductive tract allows only a strictly selected sperm subpopulation to proceed in the vicinity of an unfertilised oocyte. Female-mediated sperm selection (also known as cryptic female choice (CFC)) is far from a random process, which frequently biases paternity towards particular males over others. Earlier studies have shown that CFC is a ubiquitous phenomenon in the animal kingdom and often promotes assortative fertilisation between genetically compatible mates. Here, I demonstrate that CFC for genetic compatibility likely also occurs in humans and is mediated by a complex network of interacting male and female genes. I also show that the relative contribution of genetic compatibility (i.e. the male–female interaction effect) to reproductive success is generally high and frequently outweighs the effects of individual males and females. Together, these facts indicate that, along with male- and female-dependent pathological factors, reproductive failure can also result from gamete-level incompatibility of the reproductive partners. Therefore, I argue that a deeper understanding of these evolutionary mechanisms of sperm selection can pave the way towards a more inclusive view of infertility and open novel possibilities for the development of more personalised infertility diagnostics and treatments.