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

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 fertilization-intracytoplasmic 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.