Unilateral Varicocele Research Articles

(271) Assessment of Varicocele Bilaterality in Infertile Men

Abstract Introduction Varicocele is the most common correctable cause of male factor infertility. It has always been a debatable subject as regard how it affects fertility and the best way to treat. However, there is a wide consensus nowadays that varicocelectomy improve male fertility potentials. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. Objective The primary outcome measure was to assess disease bilaterality and the secondary outcome measure was to report on improvement in semen 3 and 6 months post varicocelectomy and pregnancy rate 1 year post surgery. Methods This prospective study was conducted between January 2019 and January 2022. Infertile males with varicoceles underwent microsurgical subinguinal varicocelectomy by expert uroandrologists. Patients who were referred as unilateral varicoceles had their CDUS repeated for assessment of missed concomitant contralateral varicocele. Then, patients who were diagnosed with bilateral varicoceles underwent bilateral subinguinal ligation straight away. Those who were referred with unilateral varicocele had their palpable sides operated on first; then the contralateral side was also explored using an intraoperative Doppler device and the maximal vein diameter was measured. Patients came for follow for at least 6 months after surgery to evaluate any complications and assess improvement in semen parameters. Gynecologists also reported on normal pregnancy rate 1 year after surgery. Results A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). This is statistically significantly higher than initial US (P<0.001). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter [r=0.9, P<0.001]. Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Conclusions Varicocele bilaterality is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome. Disclosure No.

PSII-7 Is Scrotal Ultrasound a Useful Tool in Ram Breeding Soundness examination?

Abstract Varicocele, a condition of abnormally dilated veins within the pampiniform plexus, is associated with reduced male fertility in several species but its frequency and impact in rams is not well documented. Semen was collected and pampiniform plexus ultrasound performed in early December during breeding soundness examinations (BSE) of mature Composite-IV rams over a three-year study. A portion of rams were evaluated in multiple years and data from a total of 129 collections on 90 rams were available for analyses. Semen parameters were estimated by computer-assisted sperm analysis (CASA). Imaging software was used to quantify the cross-sectional area of five vessels per testis and average areas of the left testis (AAL), right testis (AAR), and both testes (AAT) were calculated. The correlation between AAL and AAR measured on the same ram within a year was moderate and positive (0.51; P < 0.001). However, correlations between AAL, AAR, and AAT measured on the same ram in consecutive years were not different from zero. Average vessel area was analyzed with fixed effects of testis side (AAL or AAR), year (2020, 2021, or 2022), ram age (2, 3, or ≥ 4 yr-old) and a random effect of ram. Across years, AAL was 23 to 25% greater than AAR and 16 to 18% greater in ≥ 4-yr-old than younger rams (P < 0.01). Unilateral varicocele (UV) was diagnosed when AAL/AAR or AAR/AAL ratio exceeded 1.5 in a ram and, for rams sampled in multiple years, those diagnosed in one year were considered affected for all subsequent years. Within year, prevalence of UV ranged from 16 to 36%. Scrotal circumference (SC) and CASA parameters were analyzed with fixed effects of year, ram age, and UV status and a random effect of ram. Within 2- and 3-yr-olds, sperm from UV rams had lower motility than unaffected rams (42.1 ± 6.7% vs 62.2 ± 4.1% and 47.8 ± 7.4% vs 70.1 ± 4.7%, respectively; P ≤ 0.02) but no differences were observed within 4-yr-old rams. Across ages, sperm from UV rams had a lower percentage of normal than unaffected rams (91.5 ± 1.1% vs 94.3 ± 0.74%; P = 0.03). Sperm concentration, progressive motility, and SC were unaffected by UV status. Future studies will evaluate the effect UV status on siring capacity. Ultrasound methodologies previously refined to diagnose varicocele in boars helped identify sub-fertile rams that would not have been classified by routine BSE procedures. However, these methodologies would benefit from concurrent machine learning and software development to ensure imaging consistency across technicians and streamline procedures for real-time decision making. USDA is an equal opportunity provider and employer.

Bilaterality of varicocele: The overlooked culprit in male infertility. Case series study.

Varicocele is the most common correctable cause of male infertility that always has been a debatable subject as regards how it affects fertility and the best way to treat it. Proper assessment of the disease bilaterality is crucial not to miss one side and not to jeopardize treatment outcome. This study aimed to objectively assess varicocele bilaterality in infertile men aiming to improve treatment outcome in this cohort of patients. This prospective study was conducted between January 2019 and January 2022 including infertile males with varicoceles. Assessment of missed concomitant contralateral varicocele done pre-operatively by Color Doppler Ultrasound and intraoperatively by intraoperative Doppler device and measurement of maximal vein diameter of contralateral side. A total of 329 cases completed the study. A hundred cases (30.4%) were initially referred as unilateral varicoceles and 229 (69.6%) as bilateral varicoceles. After reassessment of the study population, bilaterality of varicocele was found to be as high as 98.5% (324/329). Repeat CDUS strongly correlated with the intraoperative measured varicocele diameter (r = 0.9, p < 0.001). Moreover, sperm parameters showed significant improvement 3 and 6 months post varicocelectomy. Normal pregnancy after 1 year of surgery occurred in 118 cases (35.9%). Varicocele bilaterality in infertile men is underreported. Thorough assessment by expert radiologists and andrologists is of paramount importance not to miss significant pathology or hazard treatment outcome.

Varicocelectomy's Impact on Semen Analysis in Infertile Patients

This study aimed to evaluate the effects of open subinguinal varicocelectomy on sperm parameters in infertile men. Results: The study included 70 patients with varicocele who underwent the surgery, and significant improvements were observed in semen parameters, including volume, concentration, count, motility, and morphology. Additionally, there was an increase in the likelihood of achieving pregnancy after surgery. Unilateral varicocelectomy had a greater impact on improving these parameters than bilateral varicocelectomy. Furthermore, undergoing the surgery at a younger age had a more significant impact. The mean age of patients was 27 years old, with all being married; unilateral varicocele was found in 71% of cases, while the remaining cases presented as bilateral; duration of infertility averaged around one year for all participants, with primary infertility accounting for most cases (87%). Varicocele grade II occurred among approximately one-third (34%) of participants, while grade III occurred among two-thirds (66%) of participants. No intra-operative complications were reported during or after surgeries that involved routine preoperative investigations such as physical examination and color Doppler ultrasound, along with hormonal profile analysis, before scheduling open subinguinal conventional varicocelectomies. In conclusion, this prospective descriptive study showed that subinguinal varicocelectomy improves patients' semen quality by increasing volume, concentration, count, motility, and morphology. All differences mean an increase in all parameters (volume = 0.7 ml, count = 13 million/mL, motility = 12%, and achievement of pregnancy (no = 16, 22.9%), leading to higher chances of achieving pregnancy. This effect is greater when performed unilaterally (n = 45,64.3%) than bilaterally (n = 18,25.7%), especially if done at younger ages, but further studies are needed to confirm these findings using larger sample sizes.

A Prospective study of Preoperative sonographic and Doppler parameters as predictors of improvement in semen analysis parameters after varicocelectomy

TITLE:-A Prospective study of Preoperative sonographic and Doppler parameters as predictors of improvement in semen analysis parameters after varicocelectomy OBJECTIVE:-To assess correlation between preoperative size of varicoceles, presence of reflux on sonogprahy and colour Doppler and improvement in semen analysis parameters after varicocelectomy. METHODS:-This is a prospective comparative study and was carried out between November 2021 to September 2022. During the study period, 40 consecutive patients (Patients with 16-40 years of age) presented to surgical outdoor with clinical presentation and eventual radiological diagnosis of varicocele were included. Preoperative and post operative samen anlysis was done and comparision done between semen parameters and usg color doppler findings. RESULTS: In this study, a total of 40 patients were evaluated. There was a signifificant positive correlation between the degree of reflux preoperatively and the improvement index i.e. P &lt; 0.001 in group with reflux &gt;2sec, also there was a positive correlation between the vein diameter and the improvement index i.e. P=/&lt;0.001 in group with vein size &gt;3mm. CONCLUSION: The best preoperative sonographic parameters of success of unilateral varicocele repair are the presence of normal-sized testes, high grade reflux, and large vein diameter.

Shear Wave Elastography of the Contralateral Apparently Normal Testis in Patients with Unilateral Varicocele and Abnormal Semen Parameters

Shear Wave Elastography of the Contralateral Apparently Normal Testis in Patients with Unilateral Varicocele and Abnormal Semen Parameters

TRPV1 channel in spermatozoa is a molecular target for ROS-mediated sperm dysfunction and differentially expressed in both natural and ART pregnancy failure.

Bi-directional crosstalk between Ca2+ signaling and ROS modulates physiological processes as a part of a regulatory circuit including sperm function. The role of transient receptor potential vanilloid 1 (TRPV1) in this regard cannot be undermined. This is the first report demonstrating the Ca2+-sensitive TRPV1 channel to be under-expressed in spermatozoa of subfertile men, idiopathic infertile men, and normozoospermic infertile males with high ROS (idiopathic infertility and unilateral varicocele). To study the effect of TRPV1 in determining the fertility outcome, we compared the expression profile of TRPV1 in spermatozoa of male partners who achieved pregnancy by natural conception (NC+, n = 10), IVF (IVF+, n = 23), or ICSI (ICSI +, n = 9) and their respective counterparts with failed pregnancy NC (n = 7), IVF (n = 23), or ICSI (n = 10), by both immunocytochemistry and flow-cytometry. Reduced expression of TRPV1 in sperm of IVF ± and ICSI ± men with respect to that NC+ men imply its role in mediating successful fertilization. Unsuccessful pregnancy outcome with an underexpression of TRPV1 in sperm of NC-/IVF-/ICSI-men suggests its role in conception and maintenance of pregnancy. Since ROS is regarded as one of the major contributors to sperm dysfunction, the effect of H2O2 +/- TRPV1 modulators (RTX/iRTX) on acrosomal reaction and calcium influx was evaluated to confirm TRPV1 as a redox sensor in human sperm. A significant increment in the percentage of acrosome reacted spermatozoa along with augmented Ca2+-influx was observed after H2O2 treatment, both in the presence or absence of TRPV1 agonist resiniferatoxin (RTX). The effect was attenuated by the TRPV1 antagonist iodoresiniferatoxin (iRTX), indicating the involvement of TRPV1 in mediating H2O2 response. Enhancement of motility and triggering of acrosomal reaction post TRPV1 activation suggested that disruption of these signaling cascades in vivo, possibly due to down-regulation of TRPV1 in these subfertile males. Bioinformatic analysis of the crosstalk between TRPV1 with fertility candidate proteins (reported to influence IVF outcome) revealed cell death and survival, cellular compromise, and embryonic development to be the primary networks affected by anomalous TRPV1 expression. We therefore postulate that TRPV1 can act as a redox sensor, and its expression in spermatozoa may serve as a fertility marker.

P-040 Impact of varicocele on male fertility potential: comparison of unilateral vs bilateral disease on clinical presentation and outcome of varicocelectomy

Abstract 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 &amp;lt; 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 &amp;lt; 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

P-049 Sperm GSTM3: a potential molecular biomarker for sperm quality and male (in)fertility

Abstract Study question Is sperm Glutathione S-transferase Mu 3 (GSTM3) associated to sperm physiological status and male (in)fertility? Summary answer GSTM3 is expressed in human sperm, and is associated to sperm quality and fertility, which suggests it as a potential molecular biomarker for male (in)fertility. What is known already GSTM3 is an antioxidant enzyme expressed in sperm cells that is essential for an appropriate mitochondrial function, plasma membrane stability and oxidative regulation. Previous evidence suggested sperm GSTM3 to be useful as an infertility prognosis and diagnosis tool in mammalian species. In humans, expression of sperm GSTM3 has been found to be altered in mitochondrial-impaired sperm and in sperm from patients with unilateral varicocele. However, neither has this enzyme been related to semen alterations nor has it been reported to be associated to male infertility. Study design, size, duration A total of 34 semen samples from healthy, fertile men and men referred for infertility evaluation were collected, analysed and subsequently cryopreserved. Samples were classified as fertile having normal sperm parameters (NSP; n = 10); infertile with asthenoteratozoospermia (AT; n = 8) or oligoasthenoteratozoospermia (OAT; n = 8); or with idiopathic infertility (n = 8). Finally, frozen-thawed sperm samples were assessed for DNA fragmentation, and the presence, localization and relative content of GSTM3. Protein expression of GSTM3 in sperm was compared between groupss. Participants/materials, setting, methods All samples were initially evaluated by conventional sperm analysis (ejaculate volume and pH, sperm concentration, motility and morphology). Protein expression profile of GSTM3 was determined through immunoblotting and immunolocalization assays. Sperm GSTM3 was quantified using an enzyme-linked immunosorbent assay. Spearman's rank-order correlation coefficients between GSTM3 levels and sperm quality parameters were calculated. Statistical differences between groups were determined by Kruskal-Wallis followed by Mann-Whitney U tests. Main results and the role of chance GSTM3 was found to be present in human sperm cells, and to be localized along the tail. Sperm GSTM3 was positively and significantly correlated with sperm quality parameters (concentration [Rs=0.51], morphology [Rs=0.42], total [Rs=0.60] and progressive motility [Rs=0.58]; P &amp;lt; 0.05). Sperm GSTM3 levels were compared between sperm quality groups (NSP, AT and OAT). Sperm GSTM3 levels were found to be significantly higher (P &amp;lt; 0.05) in men with NSP than in those with AT or OAT (62.1, 28.1 and 20.6 ng GSTM3/mg total protein, respectively). Finally, levels of GSTM3 in sperm were compared between fertile and infertile men. Whereas fertile and idiopathic infertile men showed similar sperm GSTM3 levels (63.7 vs. 60.0 ng GSTM3/mg total protein, respectively, P &amp;gt; 0.05), infertile men with an altered seminogram had significantly lower (P &amp;lt; 0.05) levels (24.4 ng GSTM3/mg total protein). Limitations, reasons for caution The limited sample size of the present study warrants further research and clinical trials with larger sample sets before implementing this biomarker as a molecular diagnostic tool in fertility clinics. Wider implications of the findings The use of sperm GSTM3 as a novel biomarker in fertility clinics may be translated into cost-effective, non-invasive, time-saving and accurate diagnosis of men (in)fertility. Trial registration number N/A

322 Feasibility of Loupe Assisted Subinguinal Varicocelectomy in Treatment of Male Infertility

Abstract Aim To study the impact of loupe-assisted subinguinal varicocelectomy on semen quality, serum testosterone level, and spontaneous pregnancy rate. Method The data were prospectively collected for 102 infertile men with clinical varicocele. The preoperative values of semen analysis parameters and serum testosterone level were compared with postoperative values at 6 months. Spontaneous pregnancy was assessed at 6 months. Results The mean age of patients was 31.56 ± 4.31 years. Primary infertility was reported in 86 patients, while 16 had secondary infertility. Bilateral varicocele was seen in 79 patients while 23 had a unilateral varicocele. The total sperm concentration (x106/ml) before and after varicocelectomy was 12.82 ±3.91 and 20.06 ±2.13 respectively (p&amp;lt;0.0001). The total sperm motility (%) before and after varicocelectomy was 37.67 ±7.23 and 55.46 ±4.51 respectively (p&amp;lt;0.0001). The sperm morphology (Kruger/Strict morphology criteria, %) before and after varicocelectomy was 3.11 ±0.80 and 3.70 ±0.78 respectively (p&amp;lt;0.0001). The serum testosterone level (ng/dl) before and after varicocelectomy was 323.90 ±67.81 and 396.74 ±40.88 respectively (p&amp;lt;0.0001). The Spontaneous pregnancy rate in couples with primary and secondary infertility was 18.60% and 31.25% respectively. The difference in their rates was not significant (p = 0.251). The overall spontaneous pregnancy rate was 20.5 %. Conclusions Loupe-assisted sub-inguinal varicocelectomy is a safe and effective modality for treating infertile men, particularly when provision for microscopic surgery is unavailable. However, only large-size comparative studies or multi-centric trials can confirm this.

Seminal L-Carnitine In Infertile Oligoasthenoteratozoospermic Men with Varicocele.

Background:Few studies have investigated the relationship of seminal L-Carnitine (LC) with male infertility associated with varicocele. The purpose of this prospective cross-sectional study was to assess seminal plasma LC levels in infertile oligoathenoteratozoospermic (OAT) men with varicocele.Methods:Overall, 86 men were investigated. They were divided into infertile OAT men with varicocele (n=45), infertile OAT men without varicocele (n=21), and fertile men (n=20) as a control group. According to WHO guidelines, these men were subjected to history taking, clinical examination, and semen analysis. Seminal LC levels were evaluated by the colorimetric method. Statistical comparisons were done using Kruskal-Wallis and Mann-Whitney U tests and correlations were verified by the Pearson test. P-value<0.05 was set to be statistically significant.Results:The mean seminal plasma LC levels were significantly lower in infertile OAT men with varicocele (216.3±57.1 ng/ml) compared to infertile OAT men without varicocele (252.9±62.9 ng/ml, p=0.01), or fertile men (382.8±63.6 ng/ml, p=0.001). Besides, the mean seminal plasma LC level exhibited statistically significant decreases in infertile OAT men of varicocele grade III compared to varicocele grade II cases, and in infertile OAT men with bilateral varicocele compared with unilateral varicocele cases. Collectively, there was a statistically significant positive correlation between seminal LC levels with sperm concentration, motility, and normal morphology.Conclusion:Seminal LC levels are expressively reduced in infertile OAT men with varicocele and are influenced by an increase in varicocele grade and laterality.

Varicocelectomy in adolescents – Does it safeguard future fertility? A single centre experience

There is paucity of literature comparing varicocelectomy to observant management amongst adolescent boys with hormonal and semen abnormalities resulting from high grade unilateral varicoceles and consequent testicular volume loss. Furthermore, it is not known whether surgical correction in such adolescents improves paternity rates in future compared to their non-operated cohort. The primary objective was to compare adolescent boys with unilateral high grade varicocele with associated ipsilateral testicular volume loss who were operated versus those who were not, in relation to their fertility markers (hormonal, semen parameters, and testicular volume) over a 5 year follow up period. The secondary objective was to compare the paternity rates in the respective groups over long term. This was a single center, retrospective study of a prospectively maintained database conducted from 2010 to 2020, based on a standardized protocol. All adolescent boys >15 years of age (middle and late adolescence), with grade II or III unilateral varicoceles with abnormal fertility markers, who were operated (Group A) and not operated (Group B) were included. The changes in hormonal assay, sonographic assessment, semen analysis at presentation, 1st year and the 5th year follow up amongst both the groups were collated and analysed. Primary paternity rates amongst both the groups was documented by telephonic or email conversations. Of the 182 boys referred for varicocele management, 110 boys (Group A -70 boys and Group B - 40 boys) satisfied our inclusion criteria and were analysed. Mean age at presentation amongst Group A boys was 16.5 years (15-18 years) and Group B boys was 16 years (15-18 years). Grade III varicoceles were more predominant amongst both the groups. There was a significant improvement in all Group A boys (operated) in the fertility markers from the time at presentation to the 5th year follow up (p<0.001). In Group B, (boys not operated) there was no significant improvement in the above parameters. The testicular catch up growth was 92% at the 5th year follow-up in Group A and 42% in Group B. At long term follow-up, the paternity rate was 80% and 36% in Group A and B respectively. In adolescent boys in whom hormonal assay, testicular volumes and semen characteristics are negatively affected by high grade unilateral varicoceles, surgical correction could normalize these values, thereby safeguarding their fertility in the long term.

Early Experience with Laparoscopic Surgery for Undescended Testis at a Tertiary Hospital in Ibadan (2015-2019)

Background: Undescended testis (UDT) is of concern to the patient. If not treated may be complicated by trauma, torsion, male sub-fertility, and testicular cancer. In Nigeria it is commonly treated by open orchidopexy or orchidectomy. We report our experience with the laparoscopic management of undescended testes in the Western part of Nigeria.&#x0D; Methodology: The aim of this study was to report our early experience with the laparoscopic treatment of undescended testis in our centre. The study was conducted between January 2015 and December 2019. The data studied were age, unilateral or bilateral UDT, operation performed, pre-and intra-operative findings, operation time, and the outcome. The data were represented in tables and with operative pictures. Ethical clearance was obtained.&#x0D; Results: A total 12 patients were treated which consisted of 7 children and 5 adults with a mean age of 11 (6-17) years and 35.2 (29-42) years respectively. Preoperatively, 9 patients had transperitoneal laparoscopic orchidopexy, orchidectomy or varicocelectomy. The laparoscopic findings were peeping testis (5), intraabdominal testis (8), intracanalicular (5), and one absent testis. All the post-orchidopexy testes remained in the scrotum at 18 months of follow up. In the adults, there was improvement in the semen parameters in 2 men while 3 had persistent azoospermia.&#x0D; Conclusion: In our setting, laparoscopy for undescended testis is feasible, safe, diagnostic, and therapeutic. In infertile men with undescended testis and unilateral varicocele, laparoscopic varicocelectomy results in improved semen quality.

Posterior nut-cracker syndrome: Urologist’s perspective – A mini review

Posterior Nut Cracker Syndrome (PCNS) is a rare clinical condition that occurs when the left renal vein gets compressed between the abdominal aorta and vertebral body. Posterior nutcracker phenomenon is a common anatomical abnormality, which is totally asymptomatic and diagnosed in a routinely performed abdominal imaging. The pressure gradient that develops between the renal vein and the inferior vena cava is the basic reason for all the features associated with this condition. Left renal venous entrapment would result in stagnation of blood in gonadal vessels that results in cascading effect resulting in a venous congestion and increased resistance to arterial blood flow in the kidney. Patients with pelvic congestion syndrome present with left loin pain and unilateral left varicocele. Gastrointestinal symptoms and arterial hypertension may also be the presenting symptoms. The symptoms depend upon the degree of pressure in renal veins and gonadal veins. When the dilated veins communicate with renal calyx, haematuria occurs. PNCS is best managed based on the severity of symptoms and the extent of clinical manifestations. Treatment options include conservative treatment, intra-vascular stents, chemical cauterisation, open surgical intervention and finally if everything fails, nephrectomy. PCNS is a rare entity that affects mostly females and can present with a variety of signs and symptoms. A high index of clinical suspicion is needed to achieve a prompt diagnosis. Conservative treatment is recommended for patients with mild symptoms. Severely symptomatic patients might benefit from endovascular treatment.

Hormonal evaluation in adolescents with varicocele

Varicocele is one of the most frequent disease affecting the fertility potential; OBJECTIVE: the aim of this study is to assess the correlation between clinical and radiological grade of varicocele and hormonal values. The data about adolescents with left unilateral varicocele aged between 13 and 16 years, with Tanner stage V, followed at the Authors' Institution between September 2016 and September 2019 were investigated; inclusion and exclusion criteria were created. Patients underwent standard visit, Ultrasound, Doppler velocimetry and hormonal tests (at T0 and T1). Those patients with testicular hypotrophy underwent surgery. During the study period, 75 subjects with left unilateral varicocele were enrolled; 8 patients were excluded.A total of 67 patients were then studied. Among these patients, 37 had testicular hypotrophy, while the others had normal testicular volume. There was no correlation between grade of varicocele and testicular hypotrophy (p=0.12); among those patients with testicular hypotrophy, there was a statistical correlation with the grade of spermatic vein reflux (grade 4 vs grades 1-2-3) (p=0.03). Focusing on hormonal values, there was a statistical significant difference between FSH levels, clinical grades of varicocele and grade of spermatic vein reflux: FSH levels were higher in patients with clinical grade 3 varicocele respect to patients with grade 1-2 varicocele and, in particular, patients with grade 3 varicocele, testicular hypotrophy and grade 4 spermatic vein reflux (14 patients) had higher FSH level respect to others (p=0.02). After surgery there was a significant FSH reduction. Our results demonstrate that higher grade of spermatic vein reflux is associated with testicular hypotrophy and higher FSH levels.

A rare case of right-sided varicocele in right renal tumor in the absence of venous thrombosis and IVC compression

BackgroundThe presence of unilateral right-sided varicocele hints at a serious retroperitoneal disease such as renal cell neoplasm. Such tumors are usually associated with a thrombus in renal vein or spermatic vein. We report a rare presentation of right-sided renal tumor causing right-sided varicocele in the absence of thrombus in renal vein and spermatic vein but due to an anomalous vein draining from the tumor into the spermatic vein as demonstrated by computed tomography angiogram.Case presentationA 54-yr-old hypertensive male presented with unilateral grade 3 right-sided varicocele and no other signs and symptoms. Ultrasound examination of his abdomen showed the presence of a mass lesion in the lower pole of right kidney. Computed tomography confirmed the presence of right renal mass, absence of thrombus in right renal vein or inferior vena cava. The angiographic phase of CT scan showed an anomalous vein from the tumor draining into the pampiniform plexus causing varicocele.ConclusionThe presence of right-sided varicocele should raise a suspicion hidden serious pathological retroperitoneal condition, renal malignancy in particular, and should prompt the treating physician to carry out imaging studies of the retroperitoneum and careful study of the angiographic phase of the CT scan can ascertain the pathogenesis of the varicocele.

Estimation of varicocele associated human ARG2 and NOS1 proteins and computational analysis on the effect of its nsSNPs

One of the major causes of varicocele is nitrosative stress. Two genes namely arginase 2 (ARG2) and nitric oxide synthase 1 (NOS1) are important in the mechanism of nitric oxide (NO) in the body. Semen samples from three different categories were taken, fertile (n = 20), Infertile (n = 20), and unilateral varicocele (n = 15). Quantitative estimation of ARG2 and NOS1 was carried out through the ELISA kit method. t-Test and ANOVA were calculated using Graphpad Prism. For the in silico analysis, the sequence of the proteins obtained from dbSNP was used in online tools such as nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, SNAP2, PROVEAN, SIFT, and SNPeffect for screening deleterious mutants. These mutants were further evaluated with Swiss PDB and PyMOL for recording energy minimization, Root mean square deviation (RMSD) value, TM score, Hydrogen bonding, and Comparative modeling. Further, ConSurf, Netsurf, and STRING tools were used for evaluating conserved regions, stability, and protein-protein interactions respectively. The results of ARG2 protein were, fertile = 0.168 ± 0.007 U/ml, infertile = 0.201 ± 0.004 U/ml and, varicocele = 0.092 ± 0.002 U/ml. Results of NOS1 protein were fertile = 32.61 ± 2.8 nM/mg, infertile = 19.33 ± 3.7 nM/mg and, varicocele = 54.74 ± 4.8 nM/mg. From statistical analysis, the parameters were highly significant. From the in silico retrieved data, there were 130 and 499 nsSNPs (non-synonymous SNP) in ARG2 and NOS1 respectively. After screening with online tools, 6 deleterious nsSNPs each of ARG2 and NOS1 were considered for analysis through Swiss PDB. FoldX result of A52P mutant (ConSurf score = 9) of ARG2 was found to severely affect protein stability and that of A363T mutant (ConSurf score = 9) of NOS1 revealed a structural change. A52P had a higher RMSD value and A363T of NOS1 developed a new H-bond with 580th position. In varicocele cases, the ARG2 protein is found in lower quantity. The A52P variant of this protein can cause dysfunction and induce nitrosative stress. However, in infertile cases, NOS1 protein is found in lower quantity and the A363T variant can result in a decrease in NO leading to other forms of infertility.

Hypertension and Unilateral Varicoceles in a Young Male: Harbinger of a Sinister Finding

A 26-year-old young male presented with recent onset hypertension and left-sided varicocele. On physical examination, his blood pressure was elevated and varicoceles were visible. On evaluation with computed tomography of abdomen, a large left-sided para-aortic mass was seen. His 24-hour urinary metanephrines and normetanephrines levels were within normal limits. Subsequently, the mass was excised. Tumor was excised completely after carefully dissecting it from left kidney and final histopathology revealed paraganglioma and postoperatively varicoceles disappeared.

Aberrant Upregulation of Compensatory Redox Molecular Machines May Contribute to Sperm Dysfunction in Infertile Men with Unilateral Varicocele: A Proteomic Insight

Aims: To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach. Results: Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status. Innovation: This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction. Conclusions: Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD+/NADH, and NADP+/NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.

Частота отцовства у мужчин, не оперированных по поводу варикоцеле в детском и подростковом возрасте

Feasibility of prophylactic varicocelectomy in adolescents is under discussion, which determines the importance of studying the frequency of paternity among men who were actively monitored. to evaluate a paternity rate in a group of adult men who have not undergone varicocelectomy in childhood or adolescence. The paternity rate was evaluated using a questionnaire-based survey carried out in 2018 among men who were actively monitored for unilateral varicocele with ipsilateral testicular hypotrophy during adolescence in 1999-2004. A total of 202 questionnaires were sent out checking whether the recipients were willing to have children. Median age at the time of the varicocele diagnosis was 15 years [Q1; Q3] (13-17). At the time of diagnosis, varicocele of grade III was found in 114 (93.4%) boys, and in 8 (6.6%) children, varicocele of grade II was seen. A total of 142 respondents were enrolled. Median age of the participants was 31 (29; 34). 20 men were excluded from the survey, due to prophylactic varicocelectomy (n=8, 5.6%), other reproductive diseases (n=4, 2.8%), previous radiotherapy or chemotherapy (n=2, 1.4%) and reproductive pathologies in the spouses (n=6, 4.2%). 16 (13.1%) participants were not planning to have children. Among the remaining, 9 respondents (6.6%) had no children. Varicocelectomy was carried out in 17 (16.3%) patients due to infertility, and 14 (82.3%) subsequently became fathers. 83 (78.3%) patients had one or more children as a result of spontaneous pregnancy. Paternity frequency in the surveyed group was 91.5%. Our results demonstrate high paternity frequency among men with asymptomatic left-sided varicocele accompanied by ipsilateral testicular hypotrophy during childhood and adolescence who were actively monitored without surgical treatment.