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Study question Is there a difference between unilateral and bilateral varicocele on clinical presentation and postsurgical outcome of infertile men undergoing microsurgical subinguinal varicocelectomy? Summary answer Patients with bilateral varicocele have significantly worse clinical presentation than unilateral disease. Significantly greater improvement in total motility was detected with bilateral varicocele ligation. What is known already Varicocele is a common clinical condition with significant implications on male fertility potential. In the majority of cases, varicocele is unilateral affecting the left spermatic veins. Nonetheless a minority of patients may present with bilateral clinical disease. It is not entirely clear whether patients with bilateral clinical varicocele can have a more significant deterioration in testicular function than unilateral varicocele patients. Furthermore, a clear comparison of the outcome of varicocele ligation between patients with bilateral and unilateral clinical disease has not been clearly elucidated. Study design, size, duration This retrospective chart review was conducted at a tertiary medical center and included the charts of 1170 age matched patients who underwent microsurgical subinguinal varicocelectomy over an 8 year-period. Patients were classified into 2 groups; group 1 (n = 977; those who underwent unilateral varicocelectomy) and group 2 (n = 193; those who underwent bilateral varicocelectomy). Patients with genetic abnormalities, history of orchitis or chemoradiation were excluded. Participants/materials, setting, methods Patients’ demographics, varicocele grade and laterality, semen results, sperm DNA fragmentation and hormones levels initially and 3 months following varicocele ligation were collected. Frequency, median(IQR) or mean±SD were used to report categorical and numerical values, respectively. Mann-Whitney test and Repeated measures analysis of variance were used for statistical analysis of data. A p value < 0.05 was considered significant. Main results and the role of chance The patients’ mean age and body mass index were 34.5 ± 8.2 years and 28.13 ± 5.8 Kg/m2, respectively. Left varicocele was of grade 1 in 3.5% of cases, grade 2 in 52.8% and grade 3 in 43.7% with a mean diameter of 3.9 ±0.9mm. Right varicocele was of grade 1 in 59.6% of cases, grade 2 in 31.6% and grade 3 in 8.8% with a mean diameter of 2.5 ± 0.9mm. Preoperatively, patients with bilateral varicocele had significantly lower total motility (38 [17, 53.5] % vs 45 [20, 59] %, p = 0.027) and progressive motility (6 [0, 19.7] % vs 10 [0, 25] %, p = 0.039) and significantly higher serum FSH levels (4 [2, 6.1] IU/L vs 3.2 [2, 5.4] IU/L, p = 0.042) than patients with unilateral varicocele. Following varicocele ligation, significant improvements were noted in sperm concentration, total motility and progressive motility in both groups (group 1: p < 0.001 for all; group 2: p = 0.007, 0.003 and 0.003 respectively). Between group comparisons reveal a significantly greater increase in only total motility following surgery in the bilateral varicocele group compared with the unilateral group (median difference +9 [-5, +18] % vs + 5 [-5, +17] %, p = 0.045). Limitations, reasons for caution The retrospective nature of the study is one limitation. Discrepancies in the sample size between the two groups is another limitation though this is affected by the low prevalence of right varicocele. Wider implications of the findings Bilateral clinical varicocele is more detrimental on testicular function than unilateral disease. Proper identification and concomitant treatment of right varicocele may result in a better improvement in male fertility potential. Trial registration number Not applicable

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Study question Does varicocele lead to progressive testicular dysfunction If not corrected and Can patients with long history of varicocele benefit from varicocelectomy? Summary answer Varicocele in older patients have more pronounced effect. Correction at a younger age leads to more significant improvement in testicular function and semen parameters. What is known already Varicocele is present in up to 20% of the general adult male population and is more prevalent in men with primary (40%) or secondary infertility (80%). This clinical condition is mostly asymptomatic but can present with persistent scrotal pain in about 10% of cases. More importantly, varicocele has detrimental effect on testicular function due to several pathophysiologic mechanisms including hyperthermia, tissue ischemia, oxidative stress, and reflux of adrenal metabolites. Microsurgical varicocelectomy is considered the gold standard technique with least side effects compared to other modalities. Varicocelectomy is directly associated with improvements in pain and semen parameters and fertility potential. Study design, size, duration This retrospective study was approved by the ethics committee at Hamad Medical Corporation, Doha, Qatar, and has obtained a waiver of informed consent. Records of 1500 patients undergoing microsurgical subinguinal varicocelectomy between January 2017 and July 2020 were collected. Participants/materials, setting, methods The inclusion criteria were infertile patients who presented with a clinical grade 3 varicocele. Patients who were azoospermic or severe oligozoospermic, had genetic abnormalities or received prior infertility medical treatment were excluded. Also, patients with prior history of varicocelectomy, orchidopexy or exposure to gonadotoxins were also excluded. Patients were divided in 2 groups according to age, <40years and > =40years. The preoperative semen analysis and hormonal profile pre-surgery and 6 months post-surgery were collected. Main results and the role of chance 265 patients met the inclusion criteria and were therefore enrolled for data analysis. 210 patients were <40 years and 55 patients >/=40 years at the time of varicocelectomy. The patients' mean age was 33.8±8 years. Older age was found to be significantly correlated with count (-1.42), total motility (-0.166), progressive motility (-0.193), normal morphology (-0.035), FSH (-0.255) and testosterone (-0.204). Comparing the preoperative results between the groups, older patients (>/=40years) showed significantly lower values of total motility (39% vs 48.5% P = 0.04), progressive motility (7%vs 20% P = 0.0004), FSH (4 vs 3 P = 0.005) and testosterone (14.1 vs 17.1 P = 0.002) compared with younger patients. Compared with pre operative parameters, the post operative results in patients <40years showed significant improvement in sperm concentration (33 vs 26.9 p = 0.009), total motility (55% vs 48.5% p < 0.001) and progressive motility (23.5% vs 20% p = 0.022). However, in patients >/=40years, only progressive motility improved significantly (17% vs 7% p = 0.044). By comparing the post-operative results between the groups, the improvement was significantly better in patients <40years regarding total motility (p = 0.01), progressive motility (p = 0.02) and FSH (p = 0.002). Limitations, reasons for caution Retrospective nature Limited number if cases Wider implications of the findings Varicocele will lead to progressive testicular dysfunction if not corrected at younger age Trial registration number not applicable