Deep Learning of Videourodynamics to Classify Bladder Dysfunction Severity in Patients With Spina Bifida.

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.

Ultrasound-Estimated Bladder Weight Correlates With Videourodynamic Studies in Neurogenic Bladder Dysfunction.

PURPOSE: This retrospective study was designed to evaluate which lower urinary tract ultrasound parameter(s) could predict the results of invasive urodynamic testing which are the current reference standard in the evaluation of bladder dysfunction in children with spina bifida. MATERIALS AND METHODS: Fifty eight children with spina bifida undergoing video urodynamic evaluation and a renal bladder ultrasound as their standard of care were evaluated. Quantitative and qualitative ultrasound parameters were then correlated with the videourodynamic study results which served as the reference standard. RESULTS: For bladders with ending storage pressures above 15 cm H2 O, there were increases in these ultrasound measured parameters: 1) bladder mass (P = .00019), 2) bladder/body mass ratio (P = .0059), and 3) wall thickness (P = .01). We defined the storage cost as the final storage pressure divided by the percentage of expected bladder capacity attained. These data were analyzed to compute receiver operating curves with assuming end storage pressures cutoff points of 15, 20, 30, and 40 cm H2 O. The optimal area under the curve was found for a bladder weight of 65 g and a pressure cutoff of 30 cm H2 O with a sensitivity of 75% with a specificity of 84%. CONCLUSION: Bladder weight is independent of luminal volume, can be normalized to body weight, and may serve as a clinically valuable tool for noninvasive screening to define a subset of patients with neurogenic bladder with a higher likelihood of having abnormal videourodynamic results.

Corticotropin-Releasing Hormone from the Pontine Micturition Center Plays an Inhibitory Role in Micturition.

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.

Total Motile Sperm Count in Adolescent Boys with Varicocele is Associated with Hormone Levels and Total Testicular Volume.

PURPOSE: The risk factors for future infertility in adolescents with varicocele are controversial, and little is known about the association between hormone levels and semen parameters. Semen analysis is likely the closest marker of fertility but may be difficult to obtain in some boys secondary to personal, familial or religious reasons. Identifying other clinical surrogates for abnormal semen parameters may offer an alternative for assessing varicocele severity in these boys. We hypothesized that hormone levels and total testicular volume are predictive of abnormal total motile sperm count. MATERIALS AND METHODS: We retrospectively reviewed Tanner 5 boys with palpable left varicoceles who underwent a semen analysis and had serum hormone levels tested (luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-müllerian hormone and/or total testosterone) within a 6-month period. Total testicular volume was also calculated. Abnormal total motile sperm count was defined as <9 million sperm per ejaculate. RESULTS: A total of 78 boys (median age 17.2 years, IQR 16.5-18.0) were included. Luteinizing hormone, anti-müllerian hormone and total testosterone were not correlated with any semen analysis parameter. There was a negative correlation between follicle-stimulating hormone and total motile sperm count (ρ -0.35, p=0.004) and positive correlation between inhibin B and total motile sperm count (ρ 0.50, p <0.001). Total testicular volume was significantly positively correlated with total motile sperm count (ρ 0.35, p=0.01). ROC analyses revealed an optimal follicle-stimulating hormone cutoff of 2.9, an optimal inhibin B cutoff of 204 and an optimal total testicular volume cutoff of 34.4 cc to predict abnormal total motile sperm count. CONCLUSIONS: Total motile sperm count is inversely associated with follicle-stimulating hormone levels, and directly associated with inhibin B levels and total testicular volume. Optimized cutoffs for serum follicle-stimulating hormone, inhibin B and total testicular volume may prove to be reasonable surrogates for total motile sperm count in boys who defer semen analysis for personal or religious/cultural reasons.

Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2.

Bladder dysfunction is associated with the overexpression of the intermediate filament (IF) proteins desmin and vimentin in obstructed bladder smooth muscle (BSM). However, the mechanisms by which these proteins contribute to BSM dysfunction are not known. Previous studies have shown that desmin and vimentin directly participate in signal transduction. In this study, we hypothesized that BSM dysfunction associated with overexpression of desmin or vimentin is mediated via c-Jun N-terminal kinase (JNK). We employed a model of murine BSM tissue in which increased expression of desmin or vimentin was induced by adenoviral transduction to examine the sufficiency of increased IF protein expression to reduce BSM contraction. Murine BSM strips overexpressing desmin or vimentin generated less force in response to KCl and carbachol relative to the levels in control murine BSM strips, an effect associated with increased JNK2 phosphorylation and reduced myosin light chain (MLC20 ) phosphorylation. Furthermore, desmin and vimentin overexpressions did not alter BSM contractility and MLC20 phosphorylation in strips isolated from JNK2 knockout mice. Pharmacological JNK2 inhibition produced results qualitatively similar to those caused by JNK2 knockout. These findings suggest that inhibition of JNK2 may improve diminished BSM contractility associated with obstructive bladder disease.

Urine Proteomics: Evaluation of Different Sample Preparation Workflows for Quantitative, Reproducible, and Improved Depth of Analysis.

The growing field of urinary proteomics shows promise to expand the number of biomarkers for the diagnosis and prognosis of a number of human diseases. With the rapid developments in mass spectrometry methods for proteome quantification, there exists an opportunity for improved sample processing and separation workflows to make important contributions to urine proteomic analyses. Here we evaluate the performance of four sample preparation methods: MStern, PreOmics in-StageTip (iST), suspension-trapping (S-Trap), and conventional urea In-Solution trypsin hydrolysis for nondepleted urine samples. Data-dependent acquisition (DDA) mode on a QExactive HF mass spectrometer was used for single-shot label-free data acquisition. Our results demonstrate a high degree of reproducibility within each workflow. PreOmics iST yields the best digestion efficiency, whereas the S-Trap workflow gives the greatest number of peptide and protein identifications. Using the S-Trap method and starting with ∼0.5 mL, we identify ∼1500 protein groups and ∼17 700 peptides from DDA analysis with a single injection on the mass spectrometer.

NF-κB and GATA-Binding Factor 6 Repress Transcription of Caveolins in Bladder Smooth Muscle Hypertrophy.

Caveolins (CAVs) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV protein expression is associated with impaired contraction in obstruction-induced bladder smooth muscle (BSM) hypertrophy. In this study, microarray analysis of bladder RNA revealed down-regulation of CAV1, CAV2, and CAV3 gene transcription in BSM from models of obstructive bladder disease in mice and humans. We identified and characterized regulatory regions responsible for CAV1, CAV2, and CAV3 gene expression in mice with obstruction-induced BSM hypertrophy, and in men with benign prostatic hyperplasia. DNA affinity chromatography and chromatin immunoprecipitation assays revealed a greater increase in binding of GATA-binding factor 6 (GATA-6) and NF-κB to their cognate binding motifs on CAV1, CAV2, and CAV3 promoters in obstructed BSM relative to that observed in control BSM. Knockout of NF-κB subunits, shRNA-mediated knockdown of GATA-6, or pharmacologic inhibition of GATA-6 and NF-κB in BSM increased CAV1, CAV2, and CAV3 transcription and promoter activity. Conversely, overexpression of GATA-6 decreased CAV2 and CAV3 transcription and promoter activity. Collectively, these data provide new insight into the mechanisms by which CAV gene expression is repressed in hypertrophied BSM in obstructive bladder disease.

Effect of Prenatal Repair of Myelomeningocele on Urological Outcomes at School Age.

PURPOSE: We investigated longer term urological outcomes in patients enrolled in the Management of Myelomeningocele Study (MOMS). MATERIALS AND METHODS: Women who participated in the original trial were asked for consent for followup for their child at age 6 years or older in a single comprehensive study visit to a MOMS center. Participating children underwent urological and radiologic procedures to provide objective evidence of current bladder functioning. Primary urological outcome was defined as any among need for clean intermittent catheterization, vesicostomy, urethral dilatation or augmentation cystoplasty. RESULTS: A total of 156 children were evaluated, with a mean age of 7.4 years. Overall 62% vs 87% in the prenatal and postnatal surgery groups, respectively, were placed on clean intermittent catheterization (RR 0.71, 95% CI 0.58-0.86, p <0.001). Voiding status was significantly different between the groups (p <0.001) as 24% in the prenatal group vs 4% in the postnatal group (RR 5.8, 95% CI 1.8-18.7) were reported to be voiding volitionally. Augmentation cystoplasty, vesicostomy and urethral dilation did not differ between the 2 groups. Aside from a larger post-void residual urodynamic catheterization volume, there were no other statistical differences in videourodynamic data or findings on renal/bladder ultrasound. CONCLUSIONS: Prenatal closure of myelomeningocele resulted in less reported clean intermittent catheterization at school age and the mechanism for this is unclear. Although most children are in diapers or on clean intermittent catheterization, parental reports showed children who underwent prenatal closure may be more likely to void volitionally than the postnatal group. Despite these findings, urological outcomes alone should not be the sole impetus to perform in utero closure in children with spina bifida.

Percutaneous nephrolithotomy in an 8-week-old infant.

We report successful percutaneous nephrolithotomy (PCNL) in an 8-week-old, 4.12 kg infant with a combined stone burden of > 2 cm in a solitary kidney. The patient was born with thoracolumbar myelomeningocele and had developed recurrent urinary tract infections. Her size precluded retrograde intrarenal surgery and shockwave lithotripsy would be unlikely to clear the stone burden. Stone analysis revealed hydroxyapatite and carbonate apatite stones, and metabolic work up revealed hypercalciuria for which chlorothiazide was started. To our knowledge, this is the youngest patient to undergo PCNL reported in the literature.

Intermediate-Term Followup of Proximal Hypospadias Repair Reveals High Complication Rate.

PURPOSE: Results following distal hypospadias repair are favorable. Grouping proximal and distal hypospadias repair artificially increases the perceived success rate of proximal hypospadias. We identified our complication rate of proximal hypospadias repair and hypothesized a higher complication rate for 1-stage repair. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive boys who underwent proximal hypospadias from 2007 to 2014. Proximal hypospadias was defined as a urethral meatus location at or more proximal than the penoscrotal junction after penile degloving. We further stratified boys into those with planned 1-stage vs 2-stage repair. Univariate and Cox regression analyses were performed to assess associations with covariates and compare time to the first complication, respectively. RESULTS: A total of 167 boys met study inclusion criteria. Median followup was 31.7 months for 1-stage repair in 86 patients and staged repair in 81. The overall complication rate was 56%. Complications developed in 53 of 86 1-stage (62%) vs 40 of 81 staged (49%) repairs (p = 0.11). The number of unplanned procedures per patient was higher in the 1-stage than in the staged group (0.99 vs 0.69, p = 0.06), as was the number of patients who had at least 2 complications (29 of 86 or 33% vs 13 of 81 or 16%, p = 0.03). Cox regression showed no difference in time to the first complication for staged compared to 1-stage repair (HR 0.77, 95% CI 0.43-1.39). CONCLUSIONS: Our 56% complication rate of proximal hypospadias warrants further long-term patient followup. More patients in the 1-stage group experienced at least 2 complications. However, when complications developed, they developed no differently in the 2 groups.

Voiding Dysfunction: What Can Radiologists Tell Patients and Pediatric Urologists?

OBJECTIVE: Imaging children with dysfunctional voiding remains a challenge because 98% of these children have normal anatomy. Identifying the 1-2% of children who do have an anatomic basis for incontinence is important; this article focuses on how pediatric urologists use imaging for the evaluation of patients with this condition. CONCLUSION: Imaging a patient with dysfunctional voiding can provide findings that will allow an accurate diagnosis and lead to optimal management. The key for the pediatric urologist is using imaging studies judiciously because the diagnostic yield is low. If every patient with dysfunctional voiding who presents to the clinic undergoes imaging, there will be little gain. Understanding in which patients to try imaging sooner versus trying medical and behavioral management first is a function of experience.

Mechanical stretch upregulates proteins involved in Ca2+ sensitization in urinary bladder smooth muscle hypertrophy.

Partial bladder outlet obstruction (pBOO)-induced remodeling of bladder detrusor smooth muscle (DSM) is associated with the modulation of cell signals regulating contraction. We analyzed the DSM from obstructed murine urinary bladders for the temporal regulation of RhoA GTPase and Rho-activated kinase (ROCK), which are linked to Ca(2+) sensitization. In addition, the effects of equibiaxial cell stretch, a condition thought to be associated with pBOO-induced bladder wall smooth muscle hypertrophy and voiding frequency, on the expression of RhoA, ROCK, and C-kinase-activated protein phosphatase I inhibitor (CPI-17) were investigated. DSM from 1-, 3-, 7-, and 14-day obstructed male mice bladders and benign prostatic hyperplasia (BPH)-induced obstructed human bladders revealed overexpression of RhoA and ROCK-ß at the mRNA and protein levels compared with control. Primary human bladder myocytes seeded onto type I collagen-coated elastic silicone membranes were subjected to cyclic equibiaxial stretch, mimicking the cellular mechanical stretch in the bladder in vivo, and analyzed for the expression of RhoA, ROCK-ß, and CPI-17. Stretch caused a significant increase of RhoA, ROCKß, and CPI-17 expression. The stretch-induced increase in CPI-17 expression occurs at the transcriptional level and is associated with CPI-17 promoter binding by GATA-6 and NF-κB, the transcription factors responsible for CPI-17 gene transcription. Cell stretch caused by bladder overdistension in pBOO is the likely mechanism for initiating overexpression of the signaling proteins regulating DSM tone.

Active surveillance of the adolescent with varicocele: predicting semen outcomes from ultrasound.

PURPOSE: We hypothesized that active surveillance of the adolescent varicocele is not associated with a high prevalence of suboptimal semen analysis and that patients with abnormal semen analysis have smaller testicular volumes and larger volume differentials. MATERIALS AND METHODS: We conducted an institutional review board approved retrospective cohort study of adolescents with a clinically detected varicocele. Patients were initially observed by serial scrotal ultrasound evaluating testicular size and differential. Semen analysis was routinely collected in Tanner V cases, around age 18 years. Prevalence of normal semen analysis parameters was calculated, and logistic regression was used to model the ability of age at presentation and testicular volume parameters to predict a normal semen analysis. RESULTS: A cohort of 73 patients underwent surveillance with a mean ± SD age at presentation of 15.5 ± 2.3 years. Median followup was 2.7 years, during which time subjects underwent a median of 3 scrotal ultrasounds. A low total motile count was found in 48 patients (66%). Neither age at presentation nor testicular volume differential could predict normal semen volume, density, sperm motility or total motile count. Total testicular volume from the final ultrasound predicted total motile count (p = 0.008). However, the collective observations of volume during the entire period of surveillance could not predict total motile count (p = 0.847). CONCLUSIONS: There is a high prevalence of suboptimal semen analysis in adolescents with a varicocele who are followed with active surveillance. Total testicular volume can predict total motile count at the end of adolescence but not throughout.

Effects of Rho-kinase inhibition on myosin light chain phosphorylation and obstruction-induced detrusor overactivity.

OBJECTIVES: To study the relationship between myosin light chain phosphorylation of the detrusor muscle and spontaneous smooth muscle contractions in a rabbit model of partial outlet obstruction. METHODS: New Zealand white rabbit urinary bladders were partially obstructed for 2 weeks. Rabbits were euthanized, detrusor muscle strips were hung on a force transducer and spontaneous activity was measured at varying concentrations (0-0.03 µM/L) of the Rho-kinase inhibitors GSK 576371 or 0.01 µM/L Y27632. Basal myosin light chain phosphorylation was measured by 2-D gel electrophoresis in control and GSK 576371-treated strips. RESULTS: Both drugs suppressed the force of spontaneous contractions, whereas GSK 576371 had a more profound effect on the frequency of the contractions. The IC50 values for the inhibition of frequency and force of spontaneous contractions were 0.17 µM/L and 0.023 µM/L for GSK 576371, respectively. The compound significantly decreased the basal myosin light chain phosphorylation from 28.0 ± 3.9% to 13.5 ± 1.9% (P < 0.05). At 0.01 µM/L, GSK 576371 inhibited spontaneous bladder overactivity by 50%, but inhibited carbachol-elicited contractions force by just 25%. CONCLUSIONS: These data suggest that Rho-kinase regulation of myosin light chain phosphorylation contributes to the spontaneous detrusor activity induced by obstruction. This finding could have therapeutic implications by providing another therapeutic option for myogenic, overactive bladder.

Can Videourodynamics shape management in refractory pediatric lower urinary tract dysfunction?

INTRODUCTION: Bladder dysfunction, or more specifically lower urinary tract dysfunction (LUTD), remains a common reason for pediatric urology consultation, and the management of these patients is time consuming and frustrating for patients, families and providers alike. But what happens when the patient proves refractory to current treatment modalities? Is there a role for the use of videourodynamics (VUDS) to help guide therapy in the patient with refractory voiding dysfunction, and if so how might we select patients for this invasive study in order to increase the yield of useful information? OBJECTIVES: To determine the role, if any, for VUDS in the evaluation of pediatric patients with refractory LUTD and to identify parameters that might be used to select patients for this invasive study in order to increase the yield of useful information. STUDY DESIGN: Through our IRB-approved prospectively maintained urodynamics database, we retrospectively identified 110 patients with non-neurogenic LUTD over a period from 2015 to 2022 who underwent VUDS. We excluded patients with known neurologic or anatomic lesions and developmental delay. RESULTS: There were 76 females and 34 males (69%/31%) and their average age at the time of the study was 10.5 years ± 4 with a median age of 7.3 years. Patients had been followed for a mean of 5.9 ± 3.5 office visits prior to obtaining the VUDS and reported a mean Dysfunction Voiding and Incontinence Symptom Score (DVISS) of 15.6 ± 6.7 before the VUDS. VUDS resulted in a change in management in 86 of these 110 patients (78%). Management changes included a change in medication (53/110), consideration of CIC (11/110), PTENS (1/110) and surgery (14/110). As shown in the Figure, the DVISS score was significantly higher and the number of office visits prior to VUDS was significantly higher in the 86 patients whose management was changed versus the 24 patients in whom management did not change (P < 0.02). CONCLUSION: This retrospective analysis suggests that criteria for selecting these patients include: 1) long standing urinary incontinence that is refractory to biofeedback and medications, 2) ≥6 visits to LUTD clinic with no improvement, and 3) LUT symptom score of ≥16. Our findings suggest these criteria identify a cohort of patients in which a VUDS evaluation for the child with refractory LUTD can offer a more exact diagnosis that can shape management.

Spontaneous and evoked contractions are regulated by PKC-mediated signaling in detrusor smooth muscle: involvement of BK channels.

Protein kinase C (PKC) and large conductance Ca(2+)-activated potassium channels (BK) are downregulated in the detrusor smooth muscle (DSM) in partial bladder outlet obstruction (PBOO). DSM from these bladders display increased spontaneous activity. This study examines the involvement of PKC in the regulation of spontaneous and evoked DSM contractions and whether pharmacologic inhibition of PKC in normal DSM contributes to increased detrusor excitability. Results indicate the PKC inhibitor bisindolylmaleimide 1 (Bim-1) prevented a decline in the amplitude of spontaneous DSM contractions over time in vitro, and these contractions persist in the presence of tetrodotoxin. Bim-1 also reduced the basal DSM tone, and the ability to maintain force in response to electrical field stimulation, but did not affect maximum contraction. The PKC activator phorbol-12,13-dibutyrate (PDBu) significantly reduced the amplitude and increased the frequency of spontaneous contractions at low concentrations (10 nM), while causing an increase in force at higher concentrations (1 µM). Preincubation of DSM strips with iberiotoxin prevented the inhibition of spontaneous contractions by PDBu. The BK channel openers isopimaric acid and NS1619 reduced the Bim-1-induced enhancement of spontaneous contractions in DSM strips. Our data suggest that PKC has a biphasic activation profile in the DSM and that it may play an important role in maintaining the quiescent state of the normal bladder during storage through the effects on BK channel, while helping to maintain force required for bladder emptying. The data also suggest that PKC dysfunction, as seen in PBOO, contributes to detrusor overactivity.

Comparison of semen analyses in youths with a history of cryptorchidism or varicocele.

PURPOSE: We determined relative semen quality in youths diagnosed with cryptorchidism or varicocele as a surrogate for ultimate paternity potential. We hypothesized that youths with varicocele would be at lower risk for subfertility based on semen analysis than their counterparts with surgically corrected cryptorchidism. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with a history of cryptorchidism or varicocele. Patients were placed in 1 of 3 groups based on diagnosis, including group 1-untreated varicocele, group 2-treated bilateral cryptorchidism and group 3-treated unilateral cryptorchidism. Age and semen parameters (density, volume, count, motility and total motile count) were compared for each group. RESULTS: A total of 193 subjects were studied. Median age was 18.3 (IQR 18.1-19.3), 18.6 (IQR 18.3-21.0) and 18.5 years (IQR 18.2-19.6) in the 76 group 1, 21 group 2 and 96 group 3 patients, respectively. Total motile count in groups 1, 2 and 3 was 14.6 (IQR 4.7-29.3), 4.0 (IQR 0-38.0) and 34.1 million sperm (IQR 7.6-90.8), respectively. No significant difference existed between the groups in age, volume (p = 0.106) or motility (p = 0.197). However, density (p = 0.0001), count (p = 0.0001) and total motile count (p = 0.0002) achieved significance. For each of these parameters a significant difference was noted for group 1 vs 3 and group 2 vs 3 but not for group 1 vs 2. CONCLUSIONS: The semen quality of youths with varicocele more closely resembles that of youths with bilateral cryptorchidism than those with unilateral cryptorchidism. This is concerning and should challenge current treatment paradigms for adolescents with varicocele.