Clinically, the most common genetic factors associated with male infertility are chromosomal abnormalities, Y chromosome deletion, and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations that are associated with congenital bilateral absence of vas deferens (CBAVD). The prevalence of chromosomal abnormalities in all infertile men is 5-7%. Patients with azoospermia are likely to possess sex chromosome abnormalities, and Klinefelter syndrome (47,XXY) is the most prevalent sex chromosome disorder. Conversely, oligozoospermic men are likely to have autosomal chromosome abnormalities, which include chromosomal translocation and inversion. Y chromosome deletion is the second most frequent genetic cause of spermatogenic failure after Klinefelter syndrome. The current deletion model, which has been revised according to the recombination mechanisms, includes AZFa, P5/proximal P1, P5/distal P1, P4/distal P1 and AZFc (b2/b4) deletions. The overall deletion frequency in Taiwanese infertile men is 6.5%, and AZFc (b2/b4) deletion is the most common deletion pattern, which does not show an ethnicity-specific deletion pattern in the Taiwanese population. CBAVD accounts for ∼2% of male infertility and ∼6% of obstructive azoospermia. It has been shown that CBAVD is associated with CFTR gene mutation. The mutation spectrum of the CFTR gene in Taiwanese CBAVD patients is different from that of the Caucasian population; the Taiwanese do not carry the common CFTR mutations found in Caucasians. Polymorphic polythymidine tract in intron 8 5T allele accounts for the majority (81%) of the mutant alleles in Taiwanese CBAVD. In conclusion, suggestions for current genetic testing in male infertility are as follows: karyotype analysis should be offered to all oligozoospermic men; an additional Y chromosome deletion test is recommended for men with severe oligozoospermia (< 5 × 106/mL) or non-obstructive azoospermia; and detection of CFTR gene mutation status is necessary for men with structural abnormalities of the vas deferens. Genetic testing can be helpful for reproductive decision making by physicians as well as infertile couples, which might obviate the need for assisted reproductive techniques and the production of congenital defects in the offspring.
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