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Matthew J Rabinowitz, Phillip J Huffman, Nora M Haney, Taylor P Kohn The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Taylor P KohnJames Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Marburg 134, Baltimore, MD, 21287, USAEmail tpkohn@jhmi.eduAbstract: Deletions within the male-specific region of the Y-chromosome, known as Y-Chromosome Microdeletions (YCMs), are present in as many as 5% and 10% of severe oligospermic and azoospermic men, respectively. These microdeletions are distinguished by which segment of the Y chromosome is absent, identified as AZFa (the most proximal segment), AZFb (middle), and AZFc (distal). The reported prevalence of YCMs within the world’s populations of infertile men displays vast heterogeneity, ranging from less than 2% to over 24% based on region and ethnicity. AZFc is the most commonly identified YCM, and its phenotypic presentation provides for the highest chance for fertility through artificial reproductive techniques. Conversely, deletions identified in the subregions of AZFa, AZFb, or any combination of regions containing these segments, are associated with low probabilities of achieving pregnancy. A putative mechanism explaining this discrepancy lies within the expression of autosomal, DAZ-like genes which could serve to “rescue” wild type AZFc gene expression and hence spermatogenesis. Nevertheless, recent reports challenge this dogma and stress the importance of further analysis when an AZFb deletion is detected. The screening thresholds to determine which oligospermic and azoospermic men are tested for potential YCMs has been recently contested. More recent literature supports lowering the threshold from 5 million sperm/mL of ejaculate to 1 million/mL as the frequency of YCMs in men with sperm concentrations between 1 and 5 million sperm/mL is very low (∼ 0.8%). As such, subsequent guidelines should recommend a lower screening threshold. While YCMs are extremely common globally, the understanding of their clinical significance in the field remains scattered and without consensus. Furthermore, very little is currently known about partial deletions within the AZFc region, such as b1/b3, b2/b3, and gr/gr. Hence, this review aimed to summarize and discuss modern trends in the epidemiology, screening guidelines, and clinical considerations pertaining to YCMs.Keywords: Y chromosome, abnormalities, chromosomal, gene deletion, genetics, infertility, male

Jaden R Kohn,1 Nora M Haney,2 Paige E Nichols,3 Katherine M Rodriguez,2 Taylor P Kohn2 1Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Urology, Mayo Clinic, Rochester, MN, USACorrespondence: Taylor P KohnThe James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Marburg 134, Baltimore, MD 21287, USAEmail tpkohn@jhmi.eduAbstract: Clinical varicoceles are one of the most commonly identified physical exam abnormalities in men presenting with infertility. Clinical varicoceles can cause impaired spermatogenesis and surgical correction can improve semen parameters in select men. Increasingly, andrologists are performing varicocele repairs prior to intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) to boost male fertility potential. In this review, we evaluated the available literature 1) to determine if varicocelectomy prior to IUI or assisted reproductive technologies proved to improve sperm production or pregnancy outcomes; and 2) to identify who may be the ideal candidate for pre-IUI/ART varicocelectomy. Overall, few studies have explored this topic and little can be concluded about the impact of varicocelectomy prior to IUI. The evidence, however, does support that correcting a clinical varicocele can increase pregnancy outcomes in couples who plan to pursue IVF or ICSI. When selecting patients for varicocelectomy prior to IUI or ART, clinicians should evaluate female age as improvement in semen parameters can take 6 months after varicocelectomy and this duration of time may be deleterious in cases of advanced maternal age when each cycle becomes increasingly important. Overall, the currently limited literature regarding clinical varicoceles correction demonstrates that pregnancy rates can be increased when comparing patients who have undergone varicocelectomy prior to ART with those who had clinical varicocele but did not undergo surgery.Keywords: varicocele, varicocelectomy, sperm, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection