Approximately one in twenty men has impaired spermatogenesis due to mutation of genes involved in the establishment or maintenance of fertility. Our understanding of male infertility is complicated by the variable phenotypes produced by similar genetic changes, largely due to the practise of screening a single fertility gene in isolation. This thesis aimed to increase our understanding of the role of synergistic mutations in relation to differences in semen quality. Each sample was analysed for mutation in: CAG trinucleotide repeat variation in the X-linked androgen receptor (AR) gene, micro deletion within the three Y chromosome azoospermic factor (AZF) regions, and CAG trinucleotide repeat variation and exonuclease domain mutation in the nuclear polymerase gamma (POLγ gene. These genes have been associated with reduced semen quality in past research. Each gene region was amplified by polymerase chain reaction (PCR), followed by sequencing. Suspected AZF micro-deletions were confirmed by Southern blot hybridisation. Associations with semen quality were evaluated using either a t-test or Gtest for independence at α=0.05. Yq AZF micro-deletions were observed in 6.6% (14/211) of men with poor semen quality but not in normozoospermic samples (0/104); P<0.001). Micro-deletion frequency was greatest in azoospermic and severely oligoasthenozoospermic individuals (15% and 11.5%, respectively). AR CAG repeat length ranged from 9-38 CAG repeats in the normozoospermic population (n=98) and 13-31 CAG repeats in men with poor semen quality (n= 119). Variation in AR CAG trinucleotide repeat number was not significantly related to poor semen quality (P>0.05). Variation in POLγ CAG repeat number was not significantly different between normozoospermic men (n=93) and men with poor semen quality (n= 182); P>0.05. No nucleotide changes were observed in any of the three POLγ exonuclease motifs (n=83 normozoospermic and 191 non-normozoospermic motif, 61 and 65 motif II, and 60 and 64 motif III). Although most gene regions did not show an association with poor semen quality on their own, there was a general trend towards greater severity of impaired spermatogenesis with the presence of both Yq micro-deletion and mitochondrial DNA substitutions or moderately expanded AR CAG repeats. These results support the idea that male infertility is a complex process, due to many factors, some of which act dominantly and others act in concert.