A Role for Chromosomal Microarray Testing in the Workup of Male Infertility

Abstract Genetic analysis is a critical component in the male infertility workup. For male infertility due to oligo/azoospermia, standard guidelines recommend karyotype and Y-chromosome microdeletion analyses. A karyotype is used to identify structural and numerical chromosome abnormalities, while Y-chromosome microdeletions are commonly evaluated by multiplex PCR analysis due to their submicroscopic size. Since these assays often require different vacutainer tubes to be sent to different laboratories, ordering is prone to errors. In addition, this workflow limits the ability for sequential testing and a comprehensive test result. A potential solution includes performing Y-microdeletion and numerical chromosome analysis — the most common genetic causes of oligo/azoospermia — by chromosomal microarray (CMA) and reflexing to karyotype as both assays are often offered in the cytogenetics laboratory. Such analyses can be performed using one sodium heparin vacutainer tube sample. To determine the effectiveness of CMA for the detection of clinical-significant Y-chromosome microdeletions, 21 cases with a known Y-microdeletion were tested by CytoScan HD platform. CMA studies identified all known Y-chromosome microdeletions, and in eleven (52%) cases identified additional clinically important cytogenetic anomalies, including six cases of 46,XX males, one case of isodicentric Y, two cases of a dicentric Y, and three cases of a terminal Yq deletion. These findings demonstrate that this testing strategy would simplify ordering and allow for an integrated interpretation of test results.