Can we reliably predict sperm recovery in semen of nonobstructive azoospermia men after varicocele repair?—answers are awaited

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Nonobstructive azoospermia (NOA) refers to repeated inability to detect sperm in the centrifuged pellet of semen due to primary testicular failure (1,2). NOA is not uncommon, affecting approximately 1% of all men and 10% of infertile men (3). Clinical varicocele has been implicated as a main cause of testicular dysfunction and infertility in 4.3% to 13.3% of NOA men (4-6). The widespread adoption of in vitro fertilizationintracytoplasmic sperm injection (IVF-ICSI) during the last three decades has driven more interest in varicocele repair (VR) among men with NOA and clinical varicocele. VR in NOA men has been claimed to restore spermatogenesis, induce sperm recovery in ejaculate, improve testicular sperm retrieval rates (SRRs), decrease sperm DNA fragmentation and improve pregnancy rates. Nevertheless, restoration of spermatogenesis after VR is inconsistent and the reported rates of sperm recovery are variable, ranging from 0% to 57% (4,7,8). Noteworthy, the current literature lacks reliable predictors of successful sperm recovery in ejaculate after VR. Several clinical predictors—such as age, duration of infertility, testicular volume, grade of varicocele, laterality of varicocele and serum levels of testosterone, LH, FSH and estradiol—have been studied and shown to be undependable (7-12). In contrast, testicular histology has been reported as a strong predictor of sperm recovery (3,7). Thus, identifying other more reliable prognostic factors is still welcomed. Notably, identifying gene expressions and molecular pathways involved specifically in the pathophysiology of NOA with varicocele might help predicting the outcome of VR. In a recently published report in the Journal of Urology (13), Shiraishi and his group from Japan have examined a cohort of 83 men with a mean age of 34.8 years, NOA and clinically palpable left varicocele to determine the predictors of successful sperm recovery in semen within 1 year after VR. They excluded patients with cryptorchidism or known genetic abnormalities. All patients had undergone simultaneous left sided microsurgical inguinal VR and bilateral testicular biopsies. The investigators used testicular histological patterns, genome-wide whole mRNA expression analysis (transcriptome) of testicular tissues and the number of proliferating nuclear cell antigen (PCNA) positive cells in testicular samples with maturation arrest (MA), as well as other clinical and laboratory criteria, to assess for prediction of sperm recovery after VR. In their report, 24% of patients have recovered sperm in ejaculate within 1 year, with statistically significant differences between sperm recovery rates among various histological patterns [2%, 37% and 69% in Sertoli-cell only (SCO), MA and hypospermatogenesis (HS), respectively]. Fifty three men failing to demonstrate sperm recovery after VR had undergone micro-TESE with a mean SRR of 36%. Similarly, significant SRRs differences were noted between the SCO, MA and HS patterns (20%, 57% and 100%, respectively). Transcriptome analysis screening 23,003 genes was performed to identify the 20 top-ranked genes that were differentially up-regulated or down-regulated in the testicular tissue of men with MA with or without Editorial