The genesis and consequences of DNA damage in the male germ line

July 25, 1978 saw not only the birth of the world’s first IVF baby but also what was thought to be the beginning of the end of infertility. Since that day assisted reproduction has become a widespread method for treating the infertile couple with more than 5 million children conceived through assisted reproductive technologies around the globe in 2012 (Sandin et al., 2013). There have been many advances in this period, most notably recognising that a single spermatozoon could be microinjected into the oocyte in order to bypass male infertility due to defective sperm function, paving the way for a revolution in which Intracytoplasmic Sperm Injection (ICSI) would become the primary treatment for infertility (Palermo et al., 1992). This technique gave birth to its first baby in 1992 and now, 21 years later, 1 in every 33 Australian babies is conceived as a consequence of assisted reproductive technologies (ART). Many scientists have voiced their concerns about the potential transmission of genetic defects to offspring conceived via ICSI due to the complete lack of animal trials prior to the introduction of this technique in the clinic (Aitken et al., 2013a), however the clinical focus has been on delivering a live baby and solving the couple’s infertility problem rather than the long term health trajectory of the offspring. Although the techniques for oocyte harvesting and embryo creation and culture have improved since the inception of ART, the field is still divided regarding the best form of diagnosis and course of treatment for the infertile male. This thesis aims to shed new light on the genesis and consequences of DNA damage in the male germ line- an understudied hallmark of human infertility.