Infertility is a condition that affects one in six couples, with impaired semen quality playing a significant role in at least half of all cases of infertility. Even though sperm dysfunction is a common underlying cause of infertility, many fertility clinics around the world have lost interest in investigating the cause of their patient's impaired sperm function, instead relying on mechanical treatments such as IVF-ICSI. While it is acknowledged that the advent of IVF-ICSI has been a huge advance in the treatment of the infertile male, an over-reliance on this type of "generic" treatment is potentially flawed. Evidence now suggests that reactive oxygen species (ROS) mediated damage to sperm ("oxidative stress") is a significant contributing pathology in 30-80% of cases of male infertility [1-6]. ROS produce infertility by two principal mechanisms [6]. First, ROS damage the sperm membrane, which in turn reduces the sperm's motility and ability to fuse with the oocyte (impaired fertilisation). Second, ROS directly damage the sperm DNA, compromising the paternal genomic contribution to the embryo. While IVF-ICSI undoubtedly overcomes any oxidative impairment of fertilisation, it has no therapeutic effect on the quality of the paternal genome. Therefore, the injection of sperm with oxidatively damaged DNA may result in impaired blastocyst development, an increased risk of miscarriage and the birth of a child with a sub-optimal paternal genetic compliment, potentially leading to disease in later life [7]. For all of these reasons, it is imperative that clinicians treat the underlying causes of sperm dysfunction, not just become practitioners of IVF.

The preceding chapters have conclusively established the science behind oxida-tive stress being a significant cause of male sub-fertility. Therefore, the outstanding issues facing the clinician managing patients with male factor infertility are threefold. First, the treating physician must be able to identify the presence of oxidative stress in his male patients. Second, the clinician must identify the underlying cause(s) of sperm oxidative stress and where possible, attempt to reverse or ameliorate these pathological processes responsible for damaging sperm. Finally, the clinician may initiate appropriate oral antioxidant therapy to "neutralise" any residual excess ROS left over after treating the underlying oxidative pathology. This chapter discusses each of these basic clinical issues in turn, critically analysing the available data along the way.

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