University of Southern California Institute of Urology
Introduction: It is well established that complete AZFc microdeletions are a common cause of male factor infertility. With advances in detection methodology, increasing cases of partial AZFc deletion and Yq duplication, especially those involving the AZFc region, have started to emerge. Here, we report the first series of infertile men with complete AZFc duplications. Methods: Men presenting for a fertility evaluation at a single male infertility specialty clinic from 2012-2014 who had AZFc complete duplications using a targeted microarray in peripheral blood were identified. Demographics, medical, surgical, family and reproductive history, semen and hormonal parameters, as well as response to therapies were characterized. Fischer’s exact test was used to compare the rate of complete AZFc duplications in the infertile population versus fertile controls. Results: We identified five men having complete AZFc duplications, which represented 4.8% (5/104) of men undergoing Y-chromosome microarray testing and 21% of men with men with AZFc abnormalities. The mean age was 33.7 years. There was a significantly higher proportion of AZFc duplications in the infertile population (5/104) vs. the fertile controls (0/148) (p= 0.013). The mean testicular volume was 18 mL. One man had a left grade 2 varicocele. The mean FSH was 5.5 IU/L (range 1-11 IU/L), LH 3.6 IU/L (range 3-4.2 IU/L), and testosterone 14.5 nmol/L (range 12.5-18.3 nmol/L). With respect to semen parameters, one man was persistently azoospermic. The second man alternated between severe oligospermia and rare non-motile sperm. The third man had one semen analysis demonstrating azoospermia and a second demonstrating a total sperm count (TSC) of 4 ×106. The fourth man was persistently oligospermic with TSCs ranging from 3.96-12.6 ×106. The fifth man had severe oligospermia, with a mean TSC of 1.5 ×106; after intervention (varicocele embolization, clomiphene citrate), his TSC rose to 21.7 ×106. He then fathered a spontaneous pregnancy. Conclusions: This is the first study to report that complete AZFc duplications are common in those infertile men with AZFc abnormalities, representing 21% of the AZFc alterations in this group. Studies only targeting AZFc deletions are underestimating the frequency of AZFc abnormalities in men with spermatogenic failure. They represent a heterogeneous group, having a variable reproductive potential. Cases should be managed on an individual basis. SOURCE OF Funding: None
