Many studies have investigated the suggested link between increased CAG repeat length in exon 1 of the AR gene and depressed spermatogenesis and male infertility. Studies conducted in China [10], Singapore [11], Japan [12], Australia [13], Greece [14] and France [15], have shown that longer CAG repeats are associated with defective spermatogenesis, while those conducted in Sweden [16], Finland [17], Germany [18], India [19], Italy [20] and Ireland [21], failed to find an association. The ethnic origin of the subjects and patient selection criteria have been suggested as contributing factors for the conflicting reports [20]. To clarify the relevance of CAG repeat size and male infertility, further studies with more homogeneous infertile/subfertile patients should be conducted.

We analyzed the number of CAG repeats among different subgroups of infertile/subfertile patients categorized according to their sperm counts (azoospermia, severe oligozoospermia, mild oligozoospermia and normozoospermia). All those with known causes of spermatogenic failure, such as Y microdeletions, XXY, XX males and obstructive azoospermia were analyzed as a separate subgroup consisting of patients with a known cause of infertility.

This is the first report of the distribution of AR CAG repeats among men from R. Macedonia and the first to correlate the length of AR CAG repeat tracts with the impaired spermatogenesis and male infertility. We failed to find an association between the mean number of CAG repeats among any of the infertile/subfertile subgroups and the fertile controls. However, we found a significantly higher percentage of CAG repeats >26 (p = 0.022), >27 (p = 0.018) and >28 (p = 0.009) in males with mild oligozoospermia. These results indicate a possible association between CAG repeat length and mild oligozoospermia. It is possible that long AR CAG repeat number acts as a low penetrance risk factor, which slightly impairs spermatogenesis, and probably acts in a more complex manner together with other genetic and/or environmental factors. Further studies on a larger number of patients with mild oligozoospermia are warranted to confirm the association between impaired spermatogenesis and mild oligozoospermia

Table 1. CAG repeat numbers among different groups of infertile/subfertile patients and fertile controls.