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An analysis of the frequency of Y‐chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men
Author(s) -
Johnson Mark,
Raheem Amr,
De Luca Francesco,
Hallerstrom Marcus,
Zainal Yasmeen,
Poselay Sameer,
Mohammadi Baharak,
Moubasher Amr,
Johnson Thomas Frederick,
Muneer Asif,
Sangster Philippa,
Ralph David J.
Publication year - 2019
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.14521
Subject(s) - y chromosome microdeletion , male infertility , medicine , y chromosome , azoospermia , azoospermia factor , sperm , gynecology , testicular sperm extraction , andrology , semen analysis , semen quality , infertility , population , biology , genetics , gene , pregnancy , environmental health
Objective To describe the prevalence of Y‐chromosome microdeletions in a multi‐ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing in men with Y chromosome microdeletions. Patients and Methods A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed. Results The prevalence of microdeletions was 4% ( n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZF b+c (13.8%), AZF b (6.9%), AZF a (1.7%), and partial AZF a (1.7%). A high follicle‐stimulating hormone level ( P < 0.001) and a low sperm concentration ( P < 0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of >0.5 million/ mL . Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval ( SSR ) rate after microdissection testicular sperm extraction was 33.2% in men with AZF c microdeletion. Conclusions 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.