An analysis of the frequency of Y‐chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men

Abstract

The prevalence of Y-chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P < 0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.

Clinical and molecular characterization of Y microdeletions and X‐linked CNV67 implications in male fertility: a 20‐year experience

“…A high incidence of AZF deletions in Klinefelter patients had been reported in two small studies (Mitra et al ., ; Hadjkacem‐Loukil et al ., ), in contrast with other larger studies that have not found AZF deletions in this set of patients (Choe et al ., ; Simoni et al ., ; Rajpert‐De Meyts et al ., ; Johnson et al ., ). We just found 1 partial AZFc deletion in the Klinefelter syndrome subset which supports that there is no association between microdeletions and 47,XXY karyotype and the previous findings reporting a positive association are likely to be an occasional finding.…”

“…The prevalence of Yq microdeletions in our population was 4.6% (4.0% if the analysis was limited to individuals with normal karyotype and 3.0% if only the complete AZF deletions were considered), which supports the values described in the literature (second cause for male infertility), with a global prevalence of 2–10% in infertile men (Hofherr et al ., ; Lo Giacco et al ., ; Tahmasbpour et al ., ; Wosnitzer, ; Mascarenhas et al ., ; Johnson et al ., ) and a lower frequency estimated in Europe (around 3%) (Colaco & Modi, ). Population variations seem to be responsible for the different values reported in different studies.…”

“…The literature reveals most of the clinical relevant deletions are found in patients with azoospermia or severe oligozoospermia with less than 2 9 10 6 spermatozoa/mL. Rarely, deletions can be found in patients with a sperm concentration of 2-5 9 10 6 spermatozoa/mL (Johnson et al, 2018). Deletions in patients with a sperm concentration of 5-20 9 10 6 spermatozoa/mL are extremely rare (<1%) (Krausz, 2011;Lo Giacco et al, 2013).…”

“…Y chromosome microdeletions are the only proven CNVs that interfere with spermatogenesis (Krausz et al ., ) and are the second most common genetic cause for male infertility, with a global prevalence of 2–10% in infertile men (Hofherr et al ., ; Lo Giacco et al ., ; Tahmasbpour et al ., ; Wosnitzer, ; Mascarenhas et al ., ; Johnson et al ., ) and a lower frequency estimated in Europe (around 3%) (Colaco & Modi, ). According to the current knowledge, the Y microdeletions can be complete or partial, affect different regions simultaneously, and are divided into AZFa (0.5–4%), AZFb (1–5%), AZFb+c (1–3%) and AZFc (60–80%) (Costa et al ., ; Krausz et al ., ; Colaco & Modi, ).…”

“…CNVs are thought to contribute to the high complexity of testicular failure because of submicroscopic rearrangements of 1 kb or larger, leading to deletions and duplications of individual genes, which results in numeric and genomic instability with defective cell cycle and modifications at candidate gene function and protein expression levels Redon et al, 2006). Y chromosome microdeletions are the only proven CNVs that interfere with spermatogenesis and are the second most common genetic cause for male infertility, with a global prevalence of 2-10% in infertile men (Hofherr et al, 2011;Lo Giacco et al, 2013;Tahmasbpour et al, 2014;Wosnitzer, 2014;Mascarenhas et al, 2016;Johnson et al, 2018) and a lower frequency estimated in Europe (around 3%) (Colaco & Modi, 2018). According to the current knowledge, the Y microdeletions can be complete or partial, affect different regions simultaneously, and are divided into AZFa (0.5-4%), AZFb (1-5%), AZFb+c (1-3%) and AZFc (60-80%) (Costa et al, 2008;Krausz et al, 2014;Colaco & Modi, 2018).…”