Y chromosome gr/gr deletions are a risk factor for low semen quality

Abstract

BACKGROUNDSubfertility affects one in eight couples. In up to 50 of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established causes of low semen quality. Whether a recently identified partial AZFc deletion, the gr/gr deletion, also causes low semen quality is at present unclear.METHODSWe used a dual approach to review the effect of the gr/gr deletion on semen quality. First, we conducted a systematic review and meta-analysis of previous association studies, to compare the prevalence of gr/gr deletions between azoo-/oligozoospermic men and normozoospermic men. Secondly, we studied a cohort of 1041 male partners of subfertile couples unselected for semen quality. We employed a cross-sectional design by screening all men for the gr/gr deletion and comparing the semen quality of men with and without the gr/gr deletion.RESULTSSeven studies were included in the meta-analysis. The gr/gr deletion was significantly more prevalent among azoo-/oligozoospermic men than among normozoospermic men (OR 2.4, 95 CI 1.75-3.30). In our cohort, 25 men carried a gr/gr deletion. Men with this genotype had a lower sperm concentration (median 34 × 10 6/ml versus 53 × 106/ml, P = 0.017), total sperm count (median 108 × 106 versus 152 × 106, P = 0.006) and total motile sperm count (median 20 × 106 versus 50 × 106, P = 0.010) than men without the gr/gr deletion.CONCLUSIONY chromosome gr/gr deletions significantly reduce sperm counts and are thus associated with low semen quality.