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Variations of the left renal vein can be in the form of circumaortic vein or renal collar, retro-aortic vein, additional renal vein, or multiple primary tributaries. We report a unique complex venous pattern of concomitant circumaortic and retro-aortic left renal veins associated with a fenestrated left renal artery. Two renal veins, anterior and posterior to the renal artery, originated from the renal hilum. The anterior vein was further divided into two branches. One branch passed through the fenestrated renal artery to continue as the anterior limb of the circumaortic vein. It received the suprarenal and gonadal veins and drained into the inferior vena cava. The other branch coursed posterior to the fenestrated renal artery and joined the posterior renal vein. The posterior renal vein was divided into two branches: one forming the posterior limb of the circumaortic vein, and the other continued obliquely downwards as the retro-aortic vein. Variations in the left renal vein have been implicated in several clinical conditions, such as varicocele and pelvic varices. It also plays a crucial role in renal transplantation, as the left kidney is often used as the donor organ. Even though many reports have been published on circumaortic and retro-aortic veins, the complex venous pattern associated with a fenestrated renal artery has not been reported previously.
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Background: The aim of this study was to investigate treatment outcomes in adolescents who underwent laparoscopic surgery with an ultrasonic scalpel for symptomatic varicocele compared with adolescents who underwent surgery with a polymer clip. Methods: A total of 270 adolescents with a median age of 16 (interquartile range, IQR 13-17) years were included in the study. Taking into account the laparoscopic varicocelectomy technique used, the patients were divided into two groups. In the first group (n = 151), a polymer clip was used, while in the second group (n = 119), an ultrasonic scalpel was used to resect the spermatic vessels. The primary outcome measure was the effect of the laparoscopic technique used on treatment outcomes (postoperative complications and recurrence rates). Secondary outcomes were the duration of surgery and anesthesia and the length of hospital stay. Results: The duration of the surgical procedure (12 min (IQR 11, 15) versus 15 min (12, 19), p = 0.029) and anesthesia (21.5 min (16, 29.5) versus 28 min (23, 34), p = 0.003) was shorter in the group of adolescents in whom laparoscopic varicocelectomy was performed with an ultrasonic scalpel than in the group in which a polymer clip was used. No statistically significant difference was found between the groups studied in terms of length of hospital stay, recurrence rate (p >0.999), and complications (p = 0.703). There were no cases of testicular atrophy in either group. In the group of patients who underwent laparoscopic varicocelectomy with an ultrasonic scalpel, a slightly higher incidence of hydroceles was found (n = 4, 3.4%) than in the group in which a polymer clip was used (n = 2, 1.3%) (p = 0.410). At six-month follow-up, it was found that the majority of patients showed moderate or significant improvement in the spermogram after laparoscopic varicocelectomy (n = 85, 89.5%). In addition, the subjective discomfort or pain disappeared in the majority of patients (n = 71, 93.4%). The testicular volume increased significantly in 132 adolescents (89.8%). Conclusions: Laparoscopic varicocelectomy with a polymer clip or ultrasonic scalpel is safe and effective in adolescents with symptomatic varicocele. Treatment outcomes after laparoscopic varicocelectomy are the same regardless of whether a polymer clip or an ultrasonic scalpel is used to resect the spermatic vessels. The use of an ultrasonic scalpel for resection of the spermatic vessels shortens the overall duration of surgery and anesthesia.
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Purpose: This study aimed to compare the risk of vagal reflex during microsurgical subinguinal varicocelectomy (MSV) under general anesthesia (GA) with or without additional local anesthetic (LA) spermatic cord block (SCB). Method: A single-center randomized controlled trial was conducted between January 2022 and June 2023.300 patients with left-sided grade â ¢ varicocele were randomly divided into two groups: SCB group (n = 153) and control group (n = 147)ï¼computer-generated random numbers listï¼. During MSV under GA, the SCB group was given of ropivacaine for SCB before pulling the spermatic cord, while the control group was directly lifted. The primary outcome was the reduction in the lowest heart rate in the SCB group as compared with the control group during spermatic cord traction (SCT). Secondary outcomes included the reduction in the lowest blood pressure in the SCB group as compared with the control group; and the reductions in the lowest heart rate and lowest blood pressure as compared with baseline during SCT. The number of times that surgery and medications were suspended because of symptomatic reflex bradycardia was also recorded. Adverse events were also recorded as secondary outcomes. Result: Five patients in the SCB group and 10 patients in the CG were excluded. The lowest heart rate and systolic blood pressure during SCT in the SCB group and the control group were significantly lower than the baseline values (P < 0.05). However, the decrease in the SCB group (70-73bpm VS 108-115 mmHg) was milder than that of the control groupï¼66-72 bpm VS 105-114 mmHgï¼(P < 0.05). The number of surgeries and medication pauses due to symptomatic reflex bradycardia during surgery was significantly lower in the SCB group (2 VS 1) than in the control group (9 VS 7) (P < 0.05). Conclusion: SCB can effectively reduce the vagal reflex caused by pulling the spermatic cord during MSV, and reduce the risk of anesthesia and surgery.
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Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences. Alpha-lipoic acid (ALA), a versatile antioxidant, may alleviate oxidative stress and counteract the impact of AGEs, potentially by enhancing glucose reabsorption. Alagebrium chloride (ALT711), an anti-AGE compound, exhibits promise in cardiovascular disease by disrupting AGE cross-links. This study investigates the effects of ALA and ALT-711 on testicular function in varicocele and AGEs animal models. Both AGE and varicocele were found to alter the natural trends, leading to abnormal patterns in sperm parameters, testicular functional tests, as well as the expression of CML, RAGE, and TNF-α proteins. However, the administration of ALA or ALT711 helped mitigate these effects. While ALA demonstrated a slightly greater overall benefit compared to ALT, the difference was not statistically significant.
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Glycation End Products, Advanced , Testis , Thioctic Acid , Varicocele , Male , Animals , Thioctic Acid/pharmacology , Glycation End Products, Advanced/metabolism , Testis/metabolism , Testis/drug effects , Testis/pathology , Rats , Varicocele/metabolism , Receptor for Advanced Glycation End Products/metabolism , Spermatozoa/drug effects , Spermatozoa/metabolism , Oxidative Stress/drug effects , Protective Agents/pharmacology , Antioxidants/pharmacology , Diet , Tumor Necrosis Factor-alpha/metabolism , Disease Models, Animal , Rats, Sprague-Dawley , ThiazolesABSTRACT
Varicocele causes infertility. The current study has investigated the impact of experimental varicocele on DNA methylation, demethylation, and damage in the germ cells, TESE-derived and epididymal spermatozoa. Moreover, the results were compared between epidydimal and TESE-derived spermatozoa. Finally, the varicocele-induced effect on active DNA demethylation (ADD) of male pronucleus and pre-implantation embryo development was assessed. The mature male rats were divided into control, control-sham (undergone simple laparotomy), and experimental varicocele-induced groups (n = 6/each group). The left renal vein semi-ligation was considered to induce varicocele. The expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven-translocation proteins (TET1, 2, 3), and global DNA methylation in testicular tissue, TESE, and epididymis-derived spermatozoa, and the ADD in zygotes male pronucleus as well as pre-implantation embryo development were assessed. The expression levels of DNMT1 and TET1, 2, 3 in testicles, TESE, and epididymis-derived spermatozoa were decreased in the varicocele group compared to the control and control-sham groups. The TESE-derived spermatozoa exhibited higher DNMT1, higher DNMT1, and TET 1, 2, and no change in TET3 expression compared to epididymis-derived spermatozoa. The varicocele group represented lower DNA methylation in the testicles, TESE-derived and epididymal spermatozoa, higher 5mC+ signal in male pronucleus, and a lower pre-implantation embryo development compared to control and control-sham rats. The TESE-derived spermatozoa exhibited higher 5mC protein expression compared to epididymal spermatozoa. In conclusion, varicocele can negatively impact the DNA methylation/demethylation processes impairing spermatogenesis and leading to fertilization failure, which may ultimately result in a decrease in embryo development by increasing susceptibility to DNA damage.
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Objective: To explore patients' knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP. Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other. Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤30, 31-40, and >40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15-22) vs 0 (0-6), P<0.001), attitude (26 (24-26) vs 14 (10-18), P<0.001), and practice (20 (17-24) vs 8 (6-16), P<0.001) than those who did not. A higher proportion of patients with varicocelectomy were <40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P<0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P<0.001). Knowledge, college/bachelor's degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P<0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P<0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy. Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.
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Backgrounds: In an era of advanced maternal age, there is less conclusive evidence regarding the treatment outcomes of varicocele repair for assisted reproductive technology (ART). Progress in basic research on varicocele is notable whereas there are many clinically relevant points to discuss. Methods: Based on our experience with more than 2000 cases of microsurgical varicocele repair, we focused on the effectiveness of varicocele repair, pathophysiology, surgical approaches, contributions to ART, sperm DNA fragmentation, and varicocele-associated azoospermia in this review with the aim of identifying clearer directions for basic and clinical research on varicocele. Results: Microsurgical low ligation for varicocele repair is expected to remain the gold standard for surgical therapy. Based on the findings from a number of systematic reviews and meta-analyses, negative opinions regarding the efficacy of microsurgical varicocele repair in male infertility treatment have become virtually nonexistent. However, the majority of evidence regarding surgical indications and effectiveness pertains to improvements in semen parameters or non-ART pregnancy rates. Conclusions: Further understandings regarding to pathophysiology of varicocele will likely be gained through comprehensive genetic, transcriptomic, and epigenetic analyses using blood and testicular samples from humans and we hope to develop new diagnostic methods and pharmacotherapy.
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Background Infertility affects many couples, with male factors being responsible for over half of the cases. Male infertility can arise from various testicular illnesses, such as varicocele and cryptorchidism, as well as posttesticular disorders, like ejaculation abnormalities. Infertility is defined as the inability to conceive after 12 months of unprotected sexual activity or after six months for women over 35. Diagnostic techniques such as semen analysis and scrotal ultrasonography are done to evaluate conditions like varicocele and epididymo-orchitis. This study aims to assess the diagnostic utility of ultrasonography for male infertility and compare its findings with those from surgery and clinical care. Methodology All patients were referred to the Department of Radiology, Tertiary Care Hospital, South India, for transrectal and scrotal ultrasonography, using a high-frequency transducer with a frequency of 7.5 MHz and a color Doppler when necessary. The study included all male patients with infertility and abnormal semen analysis, as well as those with infertility accompanied by scrotal abnormalities detected during clinical examination. Patients were placed in the left lateral decubitus position for the transrectal ultrasonography examination. The testes and epididymis were thoroughly examined on both sides and compared regarding symmetry, size, texture, and vascularity. Results Varicocele was the most frequent anomaly detected by both clinical examination and ultrasonography. Ultrasound detected 30 cases of varicocele, whereas clinical examination diagnosed 15 cases. Hydrocele was identified in eight cases through clinical examination and in 15 cases through ultrasound. Epididymal cysts were found in five cases via clinical examination, while both clinical examination and ultrasonography discovered epididymitis in 10 cases. Overall, the number of anomalies detected by ultrasound was significantly higher than those found by physical examination, with a statistically significant p value of 0.001. Conclusion Transrectal ultrasound provides high-resolution imaging of the prostate, seminal vesicles, and distal vas deferens, which aids in diagnosing obstructive azoospermia. Imaging is a valuable supplement to clinical examination and laboratory studies for accurately identifying anatomy and abnormalities. Both transrectal and scrotal ultrasonography offer crucial information in diagnosing male infertility. Ultrasonography is more effective in identifying pathological abnormalities than clinical palpation.
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OBJECTIVE: To find out whether the use of indocyanine green for lymphatic sparing in the laparoscopic Palomo technique reduces the incidence of postoperative hydrocele. MATERIALS AND METHODS: A comparative cohort study of varicocele patients treated with the laparoscopic Palomo technique from 2008 to 2023 was carried out. Patients were divided into two groups according to whether fluorescence lymphography (intratesticular indocyanine green) had been performed or not. Epidemiological, surgical, and clinical data, as well as complications, were recorded. A hypothesis test was conducted using the SPSS software. RESULTS: 30 patients undergoing varicocele surgery through the laparoscopic Palomo technique were included. They were divided into two groups -lymphatic sparing (n= 13) vs. spermatic vessel ligation without sparing (n= 17). Mean age at surgery was 14 years. 5 cases of postoperative hydrocele were identified in the no lymphatic sparing group. 1 of them required surgery for hydrocele treatment. No hydrocele cases were noted in the lymphography group. The difference was statistically significant (p= 0.032). There were no statistically significant differences in terms of operating times or mean hospital stay. No recurrences, postoperative testicular atrophies, or indocyanine-green-related complications were recorded. Mean follow-up was 11.4 months. CONCLUSIONS: The use of indocyanine green for lymphatic sparing in the treatment of varicocele through the laparoscopic Palomo technique significantly reduces the incidence of postoperative hydrocele.
OBJETIVOS: Comprobar si el uso del verde de indocianina para la preservación linfática en la técnica de Palomo laparoscópico reduce la incidencia de hidrocele postoperatorio. MATERIAL Y METODOS: Se realizó un estudio comparativo de cohortes históricas incluyendo los pacientes tratados de varicocele mediante Palomo laparoscópico entre 2008 y 2023. Se dividieron en 2 grupos en función de la realización de linfografía con fluorescencia (verde de indocianina intratesticular). Se recogieron datos epidemiológicos, quirúrgicos, clínicos y complicaciones. Se realizó un análisis de contraste de hipótesis utilizando el programa SPSS. RESULTADOS: Se incluyeron 30 pacientes intervenidos de varicocele mediante la técnica de Palomo laparoscópico divididos en 2 grupos: en 13 se realizó preservación linfática y en 17 ligadura de vasos espermáticos sin preservación. La edad media en el momento de la cirugía fue de 14 años. Se identificaron 5 casos de hidrocele postoperatorio en el grupo sin preservación linfática. Uno requirió intervención quirúrgica para el tratamiento del hidrocele. No se identificó ningún caso de hidrocele en el grupo de la linfografía. La diferencia resultó estadísticamente significativa, p= 0,032. No hubo diferencias estadísticamente significativas en el tiempo quirúrgico ni en la estancia media. No se objetivaron recidivas, atrofias testiculares postquirúrgicas ni complicaciones asociadas al uso del verde de indocianina. El tiempo medio de seguimiento fue 11,4 meses. CONCLUSIONES: El uso del verde de indocianina para la preservación linfática en el tratamiento del varicocele mediante Palomo laparoscópico reduce significativamente la incidencia de hidrocele postoperatorio.
Subject(s)
Indocyanine Green , Laparoscopy , Postoperative Complications , Testicular Hydrocele , Varicocele , Humans , Male , Laparoscopy/methods , Varicocele/surgery , Adolescent , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Testicular Hydrocele/surgery , Testicular Hydrocele/prevention & control , Child , Cohort Studies , Lymphography/methods , Follow-Up Studies , Coloring Agents , Incidence , Length of Stay , Operative Time , Ligation/methods , Retrospective StudiesABSTRACT
Although surgical varicocele treatment is generally considered to result in improved reproductive outcomes, we encountered a rare case of postoperative azoospermia in an infertile male patient who underwent microsurgical varicocelectomy for a palpable left-sided varicocele with concomitant cryptozoospermia. More than 1 year after varicocelectomy, the patient still had not recovered from azoospermia. Thereafter, he underwent microdissection testicular sperm extraction (micro-TESE), allowing him and his partner to obtain one good quality blastocyst via intracytoplasmic sperm injection following oocyte retrievals. Finally, the couple had a successful pregnancy following a frozen embryo transfer, and a live male infant was subsequently delivered to them at 39 weeks and 5 days. In cases of severe testicular dysfunction, varicocelectomy may worsen the postoperative semen parameters until azoospermia. Therefore, it is important to consider preoperative sperm cryopreservation and to explore the possibility of subsequent TESE.
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Objectives: To depict the basics of percutaneous spermatic vein sclero-embolization through a right basilic vein access and to qualitatively assess the reduced discomfort and pain of this access compared to the femoral one through a VAS scale. Methods: From February 2019 to March 2020, 20 varicocele sclero-embolizations through a right basilic vein were performed and retrospectively evaluated. All patients were men with a median age of 24.5 years. Treatment technique is described, as well as mean radiation dose and procedural time, and complication rates. Results: Technical success was obtained in all patients. 1 access site complication requiring conversion to femoral access occurred. 100% of patients reported only a "mild" pain ranging from 1 to 3 on VAS scale, suggesting a comfortable access for this procedure. Conclusions: Basilic vein access determines easy left and right spermatic vein catheterization, rapid ambulation as well as easy monitoring of the access site for post-procedural evaluations.
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OBJECTIVE: The specific anatomic characteristics of the right internal spermatic vein (ISV) are pivotal factors in embolism failure. However, the inherent angles and configurations of the right ISV remain incompletely explored. This study aimed to address this gap by conducting a thorough investigation into the specific anatomic characteristics of the right ISV using imaging analysis in southwest China. METHODS: This retrospective study analyzed the imaging data of 1000 male patients who underwent multidetector spiral computed tomography (MCT). Anatomic characteristics of the right ISV, including position, type, distance, and angle, were also evaluated. RESULTS: The most common anatomic type (87.8%) of the right ISV was direct drainage into the inferior vena cava, with 90% of the angles below 25.7°. There were 22 cases (2.2%) with parallel right spermatic veins. In the axial plane, the right ISV (86.4%) was located in the third and fourth quadrants. The diameter at the entrance of the right ISV ranged from 2.7-3.8 mm. When the right ISV drained into the inferior vena cava, 83% of cases were located within 40 mm distance below the ostium of the right renal vein, while during draining into the right renal vein, the average distance from the main vein was 6.3 mm. CONCLUSION: This study concluded that MCT can be used to evaluate the anatomical characteristics of the right ISV. The optimal interventional approach was through the jugular vein route to locate the ISV opening and improve the success rate of the embolization.
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OBJECTIVE: To assess the association between varicocele and hypogonadism, or erectile dysfunction. METHODS: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome. RESULTS: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele. CONCLUSION: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances.
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BACKGROUND: The dilation and torsion of testicular veins in the plexus pampiniformis causes Varicocele, which is a surgically repairable cause of male infertility. This study assessed the impact of varicocelectomy on semen characteristics, total motile sperm count (TMSC) and sperm DNA integrity in patients with severe oligoasthenoteratozoospermia (OAT). MATERIALS AND METHODS: In this prospective study, semen samples of 360 men with severe OAT who underwent varicocelectomy according to World Health Organization (WHO) criteria 2021 were studied (pre-operatively and at 6, 12, and 18 months post-operatively). RESULTS: The average age of our patients was 38.5 years. The mean spermatozoa concentration was found to be 1.60 ± 0.83 million/ml pre-operatively, while the mean post-operative concentration was 5.17 ± 1.23 million/ml at 6 months, 8.32 ± 0.98 million/ml at 12 months, and 13.51 ± 1.48 million/ml at 18 months (P<0.0001). The mean percentage of A+B motile spermatozoa was 2.92 ± 1.17% pre-operatively, 6.10 ± 1.51% at six months, 9.58 ± 1.49% at 12 months and 13.92 ± 1.88% at 18 months postoperatively (P<0.0001). The mean Modified David's morphology score was 3.80 ± 1.43% pre-operatively, 5.95 ± 1.23% at 6 months, 7.94 ± 1.18% at 12 months, and 10.82 ± 1.91% at 18 months post-operatively (P<0.0001). The mean of total motile sperm count (TMSC) was statistically improved after varicocelectomy (P<0.001). The mean of DNA fragmentation index (DFI) of the spermatozoa was 31.40 ± 0.52% pre-operatively, and post-operatively at 28.20 ± 0.32% at 6 months, 25.90 ± 0.31% at 12 months and 20.50 ± 0.40% at 18 months (P<0.001). CONCLUSION: Varicocelectomy was associated with significant improvement of sperm parameters and DNA fragmentation resulting in significant improvement of spermatogenesis quality. We believe that universalization in the routinely used sperm dispersion chromatin (SDC) test could be beneficial in the treatment of infertility.
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Microsurgical subinguinal varicocelectomy (MSV) is the gold standard for treating varicoceles. Preservation of the internal spermatic arteries (ISAs) during MSV is important for sperm production. This study aimed to evaluate the safety and efficacy of elevating systolic blood pressure (SBP) using MSV. Data from 252 consecutive adult male patients were retrospectively reviewed. The patients were divided into two groups: a traditional group that underwent conventional MSV (n = 134) and a modified group that underwent MSV with a transiently elevated SBP of 140-160 mm Hg (n = 118). Arterial identification time, unilateral operative time, number of ISAs, arterial injury rate, and other postoperative indicators, including postoperative complications and sperm parameters, were compared between the groups. All the procedures were successful. The arterial identification and unilateral operative times were significantly shorter in the modified group (31.34 ± 10.44 vs. 42.94 ± 12.39 min and 61.48 ± 8.78 vs. 76.35 ± 12.33 min, p < .01, respectively). Intraoperatively, the number of preserved ISAs was significantly higher in the modified group (1.92 ± 0.53 vs. 1.45 ± 0.32, p < .01). The arterial injury rate did not differ significantly between the groups (2.74% vs. 0%, respectively). Compared with preoperative values, sperm parameters improved significantly 6 months postoperatively. Significant differences in semen parameters or postoperative complications were not observed between the groups. Elevated intraoperative SBP can be used to rapidly, safely, and effectively identify ISAs, increase the number of retained spermatic arteries, and markedly reduce the operative time for MSV.
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Microsurgery , Varicocele , Humans , Male , Varicocele/surgery , Microsurgery/methods , Adult , Retrospective Studies , Blood Pressure , Young Adult , Arteries/surgery , Spermatozoa , Operative TimeABSTRACT
In recent decades, we have witnessed a progressive decline in male fertility. This is partly related to the increased prevalence of chronic diseases (e.g., obesity and diabetes mellitus) and risky lifestyle behaviors. These conditions alter male fertility through various non-genetic mechanisms. However, there is increasing evidence that they are also capable of causing sperm epigenetic alterations, which, in turn, can cause infertility. Furthermore, these modifications could be transmitted to offspring, altering their general and reproductive health. Therefore, these epigenetic modifications could represent one of the causes of the progressive decline in sperm count recorded in recent decades. This review focuses on highlighting epigenetic modifications at the sperm level induced by non-genetic causes of infertility. In detail, the effects on DNA methylation, histone modifications, and the expression profiles of non-coding RNAs are evaluated. Finally, a focus on the risk of transgenerational inheritance is presented. Our narrative review aims to demonstrate how certain conditions can alter gene expression, potentially leading to the transmission of anomalies to future generations. It emphasizes the importance of the early detection and treatment of reversible conditions (such as obesity and varicocele) and the modification of risky lifestyle behaviors. Addressing these issues is crucial for individual health, in preserving fertility, and in ensuring the well-being of future generations.
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OBJECTIVE: To explore the relevant factors affecting the efficacy of microscopic spermatic cord surgery and build a predictive model for postoperative pain relief. METHODS: A retrospective analysis was conducted on the clinical data of 324 patients with spermatic cord pain who visited the Department of Urology at Peking University People's Hospital between October 2015 and April 2023. This cohort included 212 patients with varicocele-related spermatic cord pain and 112 patients with idiopathic spermatic cord pain. All the patients underwent microsurgical procedures: varicocele-related pain was treated with microsurgical varicocelectomy, and idiopathic pain was treated with microsurgical denervation of the spermatic cord. The patients were categorized into effective and ineffective groups based on whether their pain had decreased by more than 50% six months post-surgery compared with pre-surgery levels. Baseline data were preliminarily screened for clinical indicators using t tests and univariate analysis. Clinical predictor variables [age, duration of pain, diameter of varicocele, patient health questionnaire-9 (PHQ-9) score, generalized anxiety disorder-7 (GAD-7) score] were selected using Lasso regression. A clinical prediction model for effective pain relief following microscopic spermatic cord surgery was constructed using Logistic regression and presented as a nomogram. The model's internal validation was performed using the bootstrap method. Its predictive power and clinical utility were evaluated through the concor-dance index, the area under the receiver operating characteristic curve, and calibration plots. RESULTS: Post-microscopic varicocele ligation, 156 patients (73.58%) experienced significant pain relief, as did 94 patients (83.93%) following microscopic denervation. Independent predictors for postoperative outcomes included age, PHQ-9 score, GAD-7 score, chronic pain duration, and varicocele diameter, differing slightly between varicocele-related and idiopathic pain groups. The models demonstrated excellent predictive ability, with areas under the curve of 0.909 and 0.913 for varicocele and idiopathic groups, respectively, and high concordance indices. CONCLUSION: The postoperative efficacy prediction model based on age, pain duration, PHQ-9 score, GAD-7 score, and varicocele diameter has good predictive ability and clinical applicability, and can be used in clinical practice.
Subject(s)
Microsurgery , Pain, Postoperative , Spermatic Cord , Varicocele , Humans , Male , Spermatic Cord/surgery , Spermatic Cord/innervation , Retrospective Studies , Pain, Postoperative/etiology , Varicocele/surgery , Varicocele/complications , Microsurgery/methods , Denervation/methods , Adult , Logistic ModelsABSTRACT
COVID-19 is a new generation of outbreaks that invade not only local emerging region, continental but also the whole globe. Varicocele on the other hand, is a testicular vascular disease that underlies 40 % of male infertility cases. Fortunately, the two diseases can be blocked through targeting one common target, NLRP3 inflammasome. Upon searching for similar drugs that gained FDA-approval in ChEMBL library along with examining their potential blockade of the receptor through docking using CB-DOCK-2, three potential approved drugs can be repurposed, ChEMBL 4297185, ChEMBL 1201749, ChEMBL 1200545 which had binding energy of -9.8 and -9.7 kcal/mol (stronger than the reference inhibitor, -9.3 kcal/mol). Also, ADME profile of the top 3 drugs showed better attributes. Also, the simulated proteins exhibited stable pattern with strong free binding energies. Among the potential inhibitor drugs ChEMBL 4297185 was found to remain inside the binding site of the protein during the 200 ns simulation time. Hence, it is anticipated to have the highest binding and thus inhibition potential against the protein. The suggested drugs, especially ChEMBL 4297185, are potentially repurposable toward treating COVID-19 and varicocele which deserve further experimental validation.
Subject(s)
COVID-19 Drug Treatment , Inflammasomes , Molecular Docking Simulation , SARS-CoV-2 , Varicocele , Humans , Male , Varicocele/drug therapy , Varicocele/metabolism , Ligands , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Inflammasomes/metabolism , Inflammasomes/antagonists & inhibitors , COVID-19/metabolism , COVID-19/virology , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Binding Sites , Drug Repositioning , Molecular Dynamics Simulation , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Protein BindingABSTRACT
Background: Varicocele is a major correctable cause of male infertility. Shear wave elastography (SWE) represents a valuable approach for assessing spermatogenesis in infertile men; however, its application in infertile men with varicocele remains unreported in the literature to date. The objective of this study was to investigate the correlation between testicular stiffness and spermatogenesis in individuals with varicocele. Methods: A total of 568 participants with left-side varicocele and 475 age-matched healthy controls were enrolled. The mean, left, and right testicular volumes (Volume-mean, Volume-L, and Volume-R), the mean elastic modulus of bilateral, left, and right testes (Emean, Emean-L, and Emean-R); the maximum elastic modulus of bilateral, left, and right testes (Emax, Emax-L, and Emax-R); the minimum elastic modulus of bilateral, left, and right testes (Emin, Emin-L, and Emin-R) were calculated. Results: Receiver operating characteristic (ROC) curves for Volume-R and Emax were constructed to identify participants with sperm concentrations below 5 million/mL. The areas under the ROC curves (AUCs) were 0.801 and 0.775, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.820 and sensitivity and specificity of 94.6% and 59.8% [95% confidence interval (CI): 0.772-0.867, P<0.01], respectively. A total of 69 participants underwent microsurgical varicocelectomy (including 42 cases with improved semen results and 27 without). The ROC curves of Emax-L and Volume-L were constructed for the differential diagnosis between the improved and unimproved groups; the AUCs were 0.723 and 0.855, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.867 (95% CI: 0.772-0.961, P<0.01) and sensitivity and specificity of 81.5% and 81.0%, respectively. Conclusions: Our findings suggest that SWE can be used for varicocele to assess testicular parenchyma damage and Volume-L combined with Emax-L offers a more accurate method for predicting semen parameter improvement after microscopic subinguinal varicocelectomy in men with varicocele.
ABSTRACT
OBJECTIVES: The Scrotal and Penile Imaging Working Group (SPIWG) of the European Society of Urogenital Radiology (ESUR) aimed to produce recommendations on the role of the radiologist in the evaluation of male infertility focused on scrotal imaging. METHODS: The authors independently performed an extensive literature Medline search and a review of the clinical practice and consensus opinion of experts in the field. RESULTS: Scrotal ultrasound (US) is useful in investigating male infertility. US abnormalities related to abnormal sperm parameters (sperm concentration, total count, motility, and morphology) are low testicular volume (TV), testicular inhomogeneity (TI), cryptorchidism, testicular microlithiasis (TML), high-grade varicocele, bilateral absence of vas deferens, bilateral dilation and echotexture abnormalities of the epididymis. The proposed ESUR-SPIWG recommendations for imaging in the evaluation of male infertility are therefore: to measure TV; investigate TI; perform annual (US) follow-ups up to age 55 in men with a history of cryptorchidism/orchidopexy and/or in men with TML plus "additional risk factors" or with "starry sky" TML; perform scrotal/inguinal US in men with nonpalpable testis; perform scrotal US in men with abnormal sperm parameters to investigate lesions suggestive of tumors; evaluate varicocele in a standardized way; evaluate the presence or absence of vas deferens; investigate the epididymis to detect indirect signs suggesting obstruction and/or inflammation. CONCLUSIONS: The ESUR-SPIWG recommends investigating infertile men with scrotal US focusing on TV, inhomogeneity, localization, varicocele, vas deferens, and epididymal abnormalities. Cryptorchidism, TML, and lesions should be detected in relation to the risk of testicular tumors. CLINICAL RELEVANCE STATEMENT: The ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility are useful to standardize the US examination, focus on US abnormalities most associated with abnormal semen parameters in an evidence-based manner, and provide a standardized report to patients. KEY POINTS: So far, ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility were not available. The ESUR-SPIWG recommends investigating infertile men with scrotal US focusing on testicular volume, inhomogeneity, localization, varicocele, vas deferens and epididymal abnormalities, and assessing cryptorchidism, testicular microlithiasis and lesions in relation to the risk of testicular tumors. The ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility are useful to standardize the US examination, focus on US abnormalities most associated with abnormal sperm parameters in an evidence-based manner, and provide a standardized report to patients.