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ABSTRACT: Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.
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PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.
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PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.
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BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.
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Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Femenino , Humanos , Incontinencia Urinaria de Urgencia , Posmenopausia , Diafragma Pélvico , Incontinencia Urinaria/tratamiento farmacológico , Estrógenos/uso terapéutico , Antagonistas Colinérgicos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.
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Líquidos Corporales , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Infecciones Urinarias , Humanos , Transportador 2 de Sodio-Glucosa , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Infecciones Urinarias/epidemiologíaRESUMEN
Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.
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PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.
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BACKGROUND: Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive treatment of ureteral stones. These agents may affect the sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random effects Mantel-Haenszel statistics. RESULTS: Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alphablockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.
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Antagonistas Adrenérgicos alfa , Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Antagonistas Adrenérgicos alfa/efectos adversos , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos alfa/uso terapéutico , Humanos , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS: PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.
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Cálculos Renales , Cálculos Urinarios , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Magnesio , Cálculos Urinarios/inducido químicamente , Cálculos Urinarios/epidemiología , Cálculos Renales/prevención & control , Ácido CítricoRESUMEN
BACKGROUND: Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke. OBJECTIVE: The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022. RESULTS: A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. CONCLUSIONS: The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.
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Nocturia , Vejiga Urinaria Neurogénica , Vejiga Urinaria Hiperactiva , Incontinencia Urinaria , Humanos , Antagonistas Colinérgicos/uso terapéutico , Nocturia/inducido químicamente , Nocturia/complicaciones , Nocturia/tratamiento farmacológico , Diafragma Pélvico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/terapia , Vejiga Urinaria Hiperactiva/etiología , Vejiga Urinaria Hiperactiva/terapia , Incontinencia Urinaria/terapiaRESUMEN
OBJECTIVE: Endourological treatment is associated with a risk of postoperative febrile urinary tract infections and sepsis. The aim of this study was to review the reported rate of infectious complications in relation to the type and modality of the endourologic procedure. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. Two electronic databases (PubMed and EMBASE) were searched. Out of 243 articles retrieved we included 49 studies after full-text evaluation. RESULTS: Random-effects meta-analysis demonstrated that retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) were associated with not significantly different odds of getting fever (OR = 1.54, 95% CI: 0.99 to 2.39; p = 0.06) or sepsis (OR = 1.52, 95% CI: 0.37 to 6.20, p = 0.56). The odds of getting fever were not significantly different for mini PCNL compared to standard PCNL (OR = 1.11, 95% CI: 0.85 to 1.44; p = 0.45) and for tubeless PCNL compared to standard PCNL (OR = 1.34 95% CI: 0.61 to 2.91, p = 0.47). However, the odds for fever after PCNL with suctioning sheath were lower than the corresponding odds for standard PCNL (OR = 0.37, 95% CI: 0.20 to 0.70, p = 0.002). The odds of getting fever after PCNL with perioperative prophylaxis were not different from the corresponding odds after PCNL with perioperative prophylaxis plus a short oral antibiotic course (before or after the procedure) (OR = 1.31, 95% CI: 0.71 to 2.39, p = 0.38). CONCLUSIONS: The type of endourological procedure does not appear to be decisive in the onset of infectious complications, although the prevention of high intrarenal pressure during the procedure could be crucial in defining the risk of infectious complications. on behalf of U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai.
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Cálculos Renales , Nefrolitotomía Percutánea , Humanos , Cálculos Renales/cirugía , Tiempo de Internación , Nefrolitotomía Percutánea/efectos adversos , Nefrolitotomía Percutánea/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: To review the role of elastography in the evaluation and decision-making of adult, infertile men with varicocele. METHODS: A systematic search using the terms (Elastography) AND (Varicocele), (Stiffness) AND (Varicocele), (Elastography) AND (Male infertility) was performed in Pubmed/Medline. Studies reporting a) elastographic characteristics in varicocele-bearing comparing to normal testicles, and b) the correlation of elastography with varicocele grading, parameters of spermatogenesis, and outcomes of varicocele treatment were selected. Exclusion criteria were animal, adolescents, abstracts, and non-English language studies. RESULTS: In total, 453 articles were identified; 11 eligible studies were selected. Several modalities were used (shear wave elastography, strain elastography, quasistatic ultrasound elastography, acoustic radiation force impulse). Varicocele-bearing testicles have significantly different stiffness and elasticity in comparison to normal and non-varicocele testicles. Although not in full agreement, elastography readings are correlated with semen parameters. Conflicting results were reported regarding grading as most of the studies failed to demonstrate a significant correlation. Shear wave elastography showed a significant correlation with the improvement in semen parameters after varicocelectomy, but the association with pregnancy rates is unknown. Finally, no studies were identified comparing elastography with other modalities. CONCLUSIONS: Elastography can detect changes in the architecture of varicocele-bearing testicles. Although the role of the modality in grading is uncertain, elastography showed a meaningful correlation with spermatogenesis parameters. Importantly, elastography readings could predict the improvement in semen parameters after varicocelectomy which is useful in terms of decision-making in infertile men with varicocele. ABBREVIATIONS: ARFI: acoustic radiation force impulse; CDUS: colour Doppler ultrasonography; DWI: diffusion-weighted imaging; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SWE: shear wave elastography; VC: varicocele.