Stesura Seveso Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 1 ORIGINAL PAPER BACKGROUND Infertility is defined as the inability to conceive after at least 12 months of regular unprotected sexual inter- course. Infertility is a worldwide complaint and is pro- jected to involve 8-12% of couples in the fertility period (1). Males are responsible for 20-30% of cases of infertil- ity and are participating in a further 20%. Male subfertil- ity is a wide range problem with almost unknown cause in most cases (1). Although various diagnostic tests are available, their interpretation is imprecise and often sub- jective. Varicocele (Vx) which is the most treatable cause of male infertility with a prevalence of 40%, is also asso- ciated with low sperm count, decreased sperm motility and increased sperm abnormal morphology (2-4). The main hypotheses were that hyperthermia, venous pres- sure, hormonal imbalance, toxic substances and reactive oxygen radicals were involved in the pathophysiology and that varicocelectomy improved the number and motility of sperms (2-4). Vx causes a progressive decline in fertility with upwards of 80% of men presenting with secondary subfertility having a Vx (5). Several studies tried to answer how Vx causes infertility. Factors includ- ed increased oxidative stress due to increased pressure on venous walls, scrotal hyperthermia, hypoxia, reflux of renal and adrenal metabolites, hormonal imbalances, the formation of antisperm antibodies and change in the sem- inal fluid composition including epididymal proteins (6- 8). Miyaoka and Esteves found that patients with both clinical and subclinical Vxs benefited from varicocelecto- my because their sperm counts went up by a lot (9). Alpha-glycerylphosphorylcholine (αGPC), one of the major phosphorus containing-choline compounds of seminal plasma, is secreted mainly by the epididymal epithelium under androgenic control (10). The organic fraction of human seminal plasma contains phosphate esters, partic- ularly αGPC, phosphorylcholine (PCh) and inorganic phos- phate (11). αGPC is synthesized by the epididymis. It originated from phosphatidylcholine (PC) and broke down into choline and α-glycerophosphate (12). PC syn- thesis in mammalian tissue occurs by Kennedy pathway with choline as one of the pillar substances that necessi- tates the removal of fatty acids by phospholipase activity Background: Varicocele (Vx) which is the most treatable cause of male infertility, is also associated with low sperm count, decreased sperm motility and increased sperm abnormal morphology. We aimed in the current study to evaluate the correlation between seminal Alpha-Glycerylphosphorylcholine (αGPC) and semen parame- ters in infertile patients pre and post sub-inguinal micro-varicoc- electomy. Methods: The current comparative prospective study was car- ried out on 20 male patients who presented to Kasr Al-Ainy Hospitals from March 2022 to March 2023 as well as 20 healthy controls. The participants were divided into groups as follow: group (1) included fertile normozoospermic men (n = 20) who served as controls. Group (2) included infertile oligoas- thenoteratozoospermia (OAT) men with varicocele (n = 20). Patients in group (2) were followed up to 3 months after micro- surgical sub-inguinal Varicocelectomy. The examination includ- ed assessment of Vx with scrotal Duplex. Semen analysis was done according to the 5th Edition of WHO manual for semen analysis. Results: The study demonstrates that αGPC level was signifi- cantly higher among fertile normozoospermic control group and infertile OAT men post varicocelectomy when compared to infertile OAT men preoperative (p < 0.001). Moreover, it demonstrates that on follow up of infertile OAT group 3 months after sub-inguinal micro-varicocelectomy, all semen parameters showed significant improvement compared to the corresponding semen parameters pre-operatively among Vxs grade II and grade III (p < 0.001, p < 0.001, respectively). A significant posi- tive correlation was found between αGPC level and semen parameters including sperm normal forms, sperm count and sperm motility. Using ROC curve, αGPC protein showed a sen- sitivity of (100%) and a specificity of (100%) at cut off value (≤ 1.975 pg/ml) in differentiation between infertile OAT patients with Vx and control fertile normozoospermic men (p < 0.001). Conclusions: αGPC may play an important role in infertility in men with Vx and correction of Vx improves the seminal αGPC level. KEy WORDS: Varicocele; Subinguinal micro-vericocelectomy; α-glycerylphosphorylcholine; Semen parameters. Submitted 22 July 2024; Accepted 29 August 2024 Correlation between seminal alpha-Glycerylphosphorylcholine and semen parameters in infertile patients pre and post sub-inguinal micro-varicocelectomy: A prospective study Ahmed Fathy Aboseif 2, Nashaat Nabil 2, Sameh Fayek GamalEl Din 1, Shaimaa Ali Abdelkareem 3, Aya Ahmed Onsi M.M.B.c.H 4, Ahmad Zaghloul 1, Amgad Elseginy 1 1 Andrology & STDs Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt; 2 Andrology & STDs Department, Beni Suef Faculty of Medicine, Beni Suef University, Beni Suef, Egypt; 3 Clinical Pathology Department, Beni Suef Faculty of Medicine, Beni Suef University, Beni Suef, Egypt; 4 Egypt Ministry of Health & Population, Cairo, Egypt. DOI: 10.4081/aiua.2025.12832 Summary Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 A. Abo Sief, N. Nabil, S.F. GamalEl Din, et al. 2 (12). Also, the synthesis of αGPC entails sequential activ- ity of a phospholipase A or alternatively, activity of a sin- gle phospholipase B. Notably, αGPC is water soluble and degraded by hydrolysis to glycerol-3-phosphate and choline catalysed by GPC phosphodiesterase activity (12). Evaluation of αGPC activity may also help find out if the epididymis is open and if sperm isn't normal. Unfortunately, there are different opinions in the litera- ture about how useful the assay is for male infertility (13). The epididymal function in semen analysis has been pre- viously recommended as the epididymis is highly involved in preparing spermatozoa for fertilization. Alpha-glucosidase, αGPC and L-carnitine were measured in sperm-free seminal plasma to determine the exact importance of these proteins in male fertility but with conflicting results (14). The objective of this study was to evaluate the effectiveness of evaluation and assessment of seminal of αGPC in infertile men before and after sub- inguinal micro-varicocelectomy. PATIENTS AND METHODS The current comparative prospective study was carried out on 20 male patients who presented to Kasr Al-Ainy Hospitals from March 2022 to March 2023 as well as 20 controls. The institutional ethical committee of Beni suef university approved the work that conforms to Helsiniki declaration 2013 (15) (FMBSREC/08032022). Inclusion criteria Any infertile case with oligoasthenoteratozoospermia (OAT) and Vx aged 20 to 30 years old. Exclusion criteria Patients suffering from azoospermia and subclinical Vx, smoking, patients with congenital anomalies or leukocy- tospermia, history of blood transfusion, iron therapy or anemia were excluded from the study Inclusion criteria of the controls They were healthy age matched individuals who were companions to the cases. The participants were divided into groups as follows: group (1) was fertile normozoospermic men (n=20) served as controls. Group (2) was infertile OAT men with Vx (n = 20). Patients in group (2) were followed up to 3 months after sub-inguinal micro-varicocelectomy. General and clinical examinations were done. The exam- ination included assessment of Vx with scrotal Duplex. Semen analysis was done according to the 5th Edition of WHO manual for semen processing (2010) (16). Clinical examination was carried out in a warm room at the standing position with/without Valsalva maneuver. Color Doppler Ultrasonography was conducted for assur- ance of Vx and its grade when one or more veins had a maximal diameter >3 mm with a retrograde flow at rest or under Valsalva maneuver. Vx was classified according to Chiou et al. (1997) and Kim et al. (2008) characterization (17-18). The ejaculates were obtained after 4-5 days of sexual abstinence into sterile containers. More than one sample was provided 2 weeks apart. Sub-inguinal micro-varicoc- electomy was done under general anaesthesia (19). Also, it was done using a surgical microscope HB Surgitech [5 Step Magnifications (4x, 6x, 10x, 16x & 25x) 45 degree Inclined Binocular Tubes, 12.5x Wide Field Eye Pieces, F = 200 mm Objective Lens, Aadesh Complex, Court Road, Near CJM Court, Ambala-134003, Haryana, India]. After hospital discharge, patients were invited to attend to follow-up visit 3 months after sub-inguinal micro-varico- celectomy. Semen samples were obtained as described above. Fertile men infertile delivered one sample only, while infertile OAT men delivered 2 samples pre and post sub-inguinal micro-varicocelectomy. Measurement of αGPC Quantitative detection of seminal αGPC was assayed by enzyme linked immunosorbent assay (ELISA) sandwich principle Human PC/CPG (Choline Phosphoglyceride ELISA kit supplied by the American research products, USA (Cat no EELH0730) according to manufacturer’s instructions. Statistical analysis of the data Data were fed to the computer and analysed using IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. The Shapiro-Wilk test was used to verify the nor- mality of distribution. Quantitative data were described using range (minimum and maximum), mean and stan- dard deviation. The significance of the obtained results was judged at the 5% level. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups with Post Hoc test (Tukey) for pairwise comparisons. Pearson coefficient was used to correlate between two normally distributed quantitative variables. Chi-square test was used to examine the rela- tionship between two qualitative variables. T Test was to assess the statistical significance of the difference between two study group means. Finally, receiver operating char- acteristic curve was used to evaluate the sensitivity and specificity for quantitative diagnostic measures that cate- gorize cases into one of two groups. The optimum cut off point was defined as that which maximized the AUC value. The area under the ROC curve (AUC) results were considered excellent for AUC values between 0.9-1, good for AUC values between 0.8-0.9, fair for AUC values between 0.7-0.8, poor for AUC values between 0.6-0.7 and failed for AUC values between 0.5- 0.6. RESULTS The sociodemographic characteristics of the participants are shown in Table 1. The study demonstrates that αGPC level was significantly higher among fertile normo- zoospermic control group and infertile OAT men post subinguinal micro-varicocelectomy when compared to infertile OAT men preoperative (p < 0.001) (Table 2). Moreover, it was demonstrated that on follow up of infer- tile OAT group 3 months after sub-inguinal micro-varic- ocelectomy, semen parameters showed significant improvement compared to the corresponding semen parameters pre-operatively among Vxs grade II and grade Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 3 Seminal alpha-glycerylphosphorylcholine III (p < 0.001, p < 0.001, respectively) (Tables 3-4). There were no significant differences among patients with Vx grade II and Vx grade III, pre and post sub-inguinal micro-varicocelectomy regarding age (Tables 3-4). Furthermore, there was a significant positive correlation between αGPC level and semen parameters including sperm normal forms, sperm count and sperm motility (Table 5). Using ROC curve, αGPC protein showed a sen- sitivity of (100%) and a specificity of (100%) at a cut off value of ≤ 1.975 pg/ml in differentiation between infertile OAT patients with Vx and control fertile normozoosper- mic men (p < 0.001) (Figure 1). Table 1. Descriptive data of the controls and group IIa (pre-operative infertile OAT with varicocele) and group IIb (Infertile OAT after sub-inguinal micro-varicocelectomy). Group I Group IIa Group IIb Test of Sig. P value (n = 20) (preoperative) (postoperative) (n = 20) (n = 20) Age (years) Min-Max 22-26 22 - 26 22-26 F = 1.037 0.361 Mean ± SD 23.7 ± 1.4 24.15 ± 1.2 24.15 ± 1.2 Median (IQR) 23.5 (22.5-25) 24.5 (23-25) 24.5 (23-25) Semen volume (ml) Min-Max 1.4-4.8 0.6-6.9 2- 5.2 F = 3.897 * 0.035 * Mean ± SD 2.7 ± 0.9 2.76 ± 1.4 3.3 ± 0.74 Median (IQR) 2.4 (2-3) 2 (1.5-3.4) 3.2 (2.8-3.9) Sperm count (106 ml) Min-Max 24 -95 1-10 10-55 F = 54.968 * < 0.001 * Mean ± SD 54.6 ± 22.4 5.33 ± 2.7 31.5 ± 12.3 Median (IQR) 56 (65-70) 5 (2.6-8.2) 35 (16.3-40) Total sperm motility (%) Min-Max 35-65 5-25 35-65 F = 66.216 * < 0.001 * Mean ± SD 53.5 ± 7.3 14 ± 5.5 49.3 ± 9.1 Median (IQR) 55 (50-60) 15 (10-18.8) 50 (41.3-55) SD = Standard deviation; IQR = Inter Quartile Range; p value was calculated using ANOVA test. Table 2. Comparison between controls and groups IIa and IIb regrading αGPC level and normal forms. Group I Group IIa Group IIb Test of Sig. P value (controls) (preoperative) (postoperative) (n = 20) (n = 20) (n = 20) αGPC level (pg/ml) Min-Max 2.65-9.86 0.3-1.30 2.0-10.86 F = 68.589 * < 0.001 * Mean ± SD 6.66 ± 2.11 0.6 ± 0.31 6.38 ± 2.32 Median (IQR) 7.05 (5-8.2) 0.54 (0.33-0.96) 6.20 (3.2-6.9) p1 < 0.001 * 0.123 * p2 < 0.001 * Sperm normal forms (%) Min-Max 5.0-7.0 1-2 4.0-7.0 F = 49.468 * < 0.001 * Mean ± SD 6.33 ± 0.8 1.7 ± 0.47 5.35 ± 0.93 Median (IQR) 6.0 (50-60) 2.0 (1-2) 5.0 (2-4) p1 < 0.001 * 0.061 p2 < 0.001 * SD = Standard deviation; IQR: Inter Quartile Range; F: F for ANOVA test, pairwise comparison bet. each 2 groups were done using Post Hoc Test (Tukey); p: p value for comparing between the 3 groups (group I and group II a and group IIb); p1: p value for comparing between group I and group IIa (pre-operative) and Group IIb (post-operative); p2: p value for comparing between group IIa (pre-operative) and group IIb (post-operative). Table 3. Data of infertile men with varicocele grade II pre and post sub-inguinal micro-varicocelectomy. Patients with Vx grade II Group IIa (n = 11) Group IIb (n = 11) Test of Sig. P value (preoperative) (postoperative) Age (years) Min-Max 22.0-26.0 22.0-26.0 t = 0.07 0.949 Mean ± SD 24.33 ± 1.15 24.33 ± 1.15 Sperm count (106 ml) Min-Max 1-10 10-45 t = 5.41 * < 0.001 * Mean ± SD 5.14 ± 2.99 27.73 ± 14.85 Total sperm motility (%) Min-Max 5-25 35-65 t = 9.71 * < 0.001 * Mean ± SD 13.75 ± 5.9 46.82 ± 11.46 Alpha GPC level (pg/ml) Min-Max 0.03-1.3 2-6.7 t = 12.18 * < 0.001 * Mean ± SD 0.63 ± 0.24 5.58 ± 1.47 Sperm normal forms (%) Min-Max 1-2 4-6 t = 8.38 * < 0.001 * Mean ± SD 1.68 ± 0.49 4.27 ± 0.65 SD = Standard deviation; t: Student t-test; p: p value for comparing between the studied categories. Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 A. Abo Sief, N. Nabil, S.F. GamalEl Din, et al. 4 +DISCUSSION In our study, analysis of semen parameters revealed that infertile OAT men with Vx showed statistically significant decrease regarding sperm counts and percentage of motile sperms when compared to fertile normozoosper- mic men who had normal basic semen paramaters. On follow up of infertile OAT group 3 months after sub- inguinal micro-varicocelectomy, semen parameters Table 4. Data of infertile men with varicocele grade III pre and post sub-inguinal micro-varicocelectomy. Patients with Vx grade III Group IIa (n = 9) Group IIb (n = 9) Test of Sig. P value Age (years) Min – Max 22.0 – 26.0 22.0 – 26.0 t= 0.20 0.841 Mean ± SD 23.87 ± 1.35 23.87 ± 1.35 Sperm count (106 ml) Min – Max 5.75 20 - 55 t=9.33* <0.001* Mean ± SD 5.75 ± 3.56 33.78 ± 8.93 Total sperm motility (%) Min – Max 5 - 20 35 - 65 t=11.19* <0.001* Mean ± SD 14.45 ± 5.6 52.78 ± 8.33 Alpha GPC level (pg/ml) Min – Max 0.18 - 0.98 5 – 10.9 t=15.28* <0.001* Mean ± SD 0.59 ± 0.26 9.14 ± 1.62 Sperm normal forms (%) Min – Max 1 - 2 5 - 7 t=11.10* <0.001* Mean ± SD 1.75 ± 0.46 6.33 ± 1.0 SD = Standard deviation; t: Student t-test; p: p value for comparing between the studied categories. Table 5. Correlations between different parameters in the current study. Age Semen volume Sperm count Total sperm αGPC level Sperm normal (years) (ml) (10^6 ml) motility (%) (pg/ml) forms (%) Age (years) r 1.0 0.013 -0.097 -0.098 -0.109 -0.109 P 0.919 0.462 0.458 0.408 0.408 Sperm count (106 ml) r 1.0 0.691 * 0.691 * 0.744 * P < 0.001 * < 0.001 * < 0.001 * Total sperm motility (%) r 1.0 0.831 * 0.893 * P < 0.001 * < 0.001 * Alpha GPC level (pg/ml) r 1.0 0.886 * P < 0.001 * Sperm normal forms (%) r 1.0 P r: Pearson coefficient. Figure 1. ROC curve showing α-GPC level (pg/ml) to discriminate between infertile OAT patients with varicocele and controls. Figure 2. ROC showing α-GPC level (pg/ml) to discriminate between infertile OAT patients with varicocele before and after varicocelectomy. Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 5 Seminal alpha-glycerylphosphorylcholine showed significant improvement compared to the corre- sponding semen parameters pre-operatively. In agree- ment with our results, Shabana et al. reported that sperm count and progressive motility significantly improved after varicocelectomy compared to pre-operative analysis (20). Consistently, Rehman et al. reported that sperm count, motility and normal morphology were significant- ly lower in Vx patients in comparison to normal individ- ual (21). This result agreed with a large-scale study of 7035 healthy young men from general European popula- tions demonstrated that the presence of Vx was associat- ed with poorer semen quality (22). Evidence from both animal and human studies show that varicocele affects sperm quality. Experimental Vx has been associated with impairment of testicular and epididymal endocrine and exocrine function, which may contribute to infertility seen in men with Vx (23). Moreover, we found that nor- mal forms of sperms significantly improved in cases of Vx grade III compared to cases of Vx grade II after sub- inguinal micro-varicocelectomy. Consistently, Pasqualotto et al. did a study on 61 men with Vx (24). They found that men with large varicoceles have worse sperm param- eters before surgery, but they improve more after surgery than men with small or medium-sized varicoceles (24). Krishna Reddy et al. showed that patients with grade III Vx not only have better sperm parameters after surgery than those with grades I and II, but also have a significant increase in testicular volume, which goes along with improvement in sperm parameters (25). In our current study, on follow up of infertile OAT group 3 months after sub-inguinal micro-varicocelectomy, semen parameters and αGPC showed significant improvement compared to the corresponding semen parameters pre- operatively among Vx grades II and III. In our study, we believe that αGPC levels decrease in infertile men with Vx this may be related to hyperthermia, venous pressure and reactive oxygen radicals which could be involved in the pathophysiology of the devastating impact of Vx on sper- matogenesis. In the current study levels of seminal αGPC were significantly higher post sub-inguinal micro-varicoc- electomy compared to pre-operative in infertile males with Vx. Seminal αGPC were nearly matching to levels of fertile normozoospermic men after sub inguinal micro-varicoc- electomy. Statistically significant positive correlation was found between αGPC level and semen parameters. Also, the current study did not demonstrate a relation between age and αGPC level. Seminal αGPC showed 100% sensi- tivity and 100% specificity in differentiation between infertile OAT patients with Vx and fertile normozoosper- mic men. Same values of sensitivity and specificity were obtained when comparing seminal αGPC between infertile OAT patients with Vx and post sub-inguinal micro-varico- celectomy. Camargo et al. conducted a study to determine the seminal plasma lipid fingerprints in adults with Vx before and after varicocelectomy (26). They reported that αGPC levels improved in the post-varicocelectomy group (26). Seminal αGPC is one of the three main epididymal markers important for proper spermatogenesis. One of the physiological functions attributed to αGPC is a possible role in respiration and motility of sperm (27). In the same context, Mieusset et al. (2020) reported significantly lower levels of αGPC in azoospermic men (28). This finding indi- cated the possible significant role played by αGPC in male fertility. In contrast, Mieusset et al. previously reported (1988) no major difference in the total seminal content of αGPC among fertile and infertile men (29). Furthermore, Zhang et al. reported that levels of αGPC in asthenozoospermic men were significantly higher com- pared to healthy controls (30). Admittedly, small sample size is considered the main limitation of the current study as well as short follow up period. However, the prospec- tive nature of the study can add strength to the current findings. CONCLUSIONS Seminal αGPC may play an important role in infertility in men with Vx and correction of Vx improves seminal αGPC level. REFERENCES 1. Agarwal A, Baskaran S, Parekh N, et al. Male infertility. Lancet. 2021; 397:319-333. 2. Mostafa T, Rashed LA, Osman I, Marawan M. Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele. Andrologia. 2015; 47: . 3. Jensen CFS, Østergren P, Dupree JM, et al. Varicocele and male infertility. Nat Rev Urol. 2017; 14:523-533. 4. Choy JT, Eisenberg ML. Male infertility as a window to health. Fertil Steril. 2018; 110:810-814. 5. Fang Y, Su Y, Xu J, et al. Varicocele-mediated male infertility: From the perspective of testicular immunity and inflammation. Front Immunol. 2021; 12:729539. 6. Al Bakri A, Lo K, Grober E, et al. Time for improvement in semen parameters after varicocelectomy. J Urol. 2012; 187:227-231. 7. Nork JJ, Berger JH, Crain DS, Christman MS. Youth varicocele and varicocele treatment: a meta-analysis of semen outcomes. Fertil Steril. 2014; 102:381-387. 8. Elbardisi H, El Ansari W, Majzoub A, Arafa M. Does varicocelec- tomy improve semen in men with azoospermia and clinically palpa- ble varicocele?. Andrologia. 2020; 52:e13486. DECLARATIONS Ethical approval: This study was approved by the institution- al ethical committee of Beni Suef University. Additionally, informed consent was obtained from the patients. Availability of data and material: All inquiries can be directed to the corresponding author. Competing interests: The authors declare no competing interests. Funding: This study did not receive any fund. Authors' contributions: SFG drafted the initial manuscript; SFG revised the article critically; SFG reviewed and edited the article; NN designed the study; SAA performed the lab work of the study; AO, AE, AZ, AAS collected and analyzed the data. All authors reviewed the manuscript. Acknowledgments: We would to thank the surgeons who per- formed the sub inguinal micro-varicocelectomy. Archivio Italiano di Urologia e Andrologia 2025; 97(1):12832 A. Abo Sief, N. Nabil, S.F. GamalEl Din, et al. 6 9. Miyaoka R, Esteves SC. A critical appraisal on the role of varico- cele in male infertility. Adv Urol. 2012; 2012:597495. 10. Ma JY, Lee MY, Kim HM, et al. Shibimijihwang-tang elevates intracellular ATP and choline content in the cerebral cortex of ovariectomized rats. J Ethnopharmacol. 2000; 72:77-85. 11. López Rodríguez A, Rijsselaere T, Beek J, et al. Boar seminal plasma components and their relation with semen quality. Syst Biol Reprod Med. 2013; 59:5-12. 12. Gallazzini M, Burg MB. What’s new about osmotic regulation of glycerophosphocholine. Physiology. 2009; 24:245-249. 13. Ramm SA. Seminal fluid and accessory male investment in sperm competition. Philos Trans R Soc Lond B Biol Sci. 2020; 375:20200068. 14. Dacheux JL, Dacheux F, Druart X. Epididymal protein markers and fertility. Anim Reprod Sci. 2016; 169:76-87. 15. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310:2191-2194. 16. World Health Organization (WHO). WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO: 2010. 271 p. 17. Chiou RK, Anderson JC, Wobig RK, et al. Color-Doppler ultra- sound criteria to diagnose varicoceles: correlation of a new scoring system with physical examination. Urology 1997; 50:953-956. 18. Kim HH, Goldstein M. Adult varicocele. Curr Opin Urol. 2008; 18:608-612. 19. Lee JY, Yu HS, Ham WS, et al. Microsurgical intermediate sub- inguinal varicocelectomy. Int Surg. 2014; 99:398-403. 20. Shabana W, Teleb M, Dawod T, et al. Predictors of improvement in semen parameters after varicocelectomy for male subfertility: A prospective study. Can Urol Assoc J. 2015; 9:E579. 21. Rehman KU, Zaneb H, Qureshi AB, et al. Correlation between testicular hemodynamic and semen quality indices in clinical varico- cele patients in Pakistan. BioMed Res Int. 2019; 2019:7934328. 22. Damsgaard J, Joensen UN, Carlsen E, et al. Varicocele is associ- ated with impaired semen quality and reproductive hormone levels: a study of 7035 healthy young men from six European countries. Eur Urol. 2016; 70:1019-1029. 23. Birowo P, Tendi W, Widyahening IS, et al. The benefits of varic- ocele repair for achieving pregnancy in male infertility: A systematic review and meta-analysis. Heliyon. 2020; 6:e05439. 24. Pasqualotto FF, Lucon AM, Sobreiro BP, et al. Effects of medical therapy, alcohol, smoking, and endocrine disruptors on male infertil- ity. Rev Hosp Clin Fac Med Sao Paulo. 2004; 59:375-82. 25. Krishna Reddy SV, Basha Shaik A, Sailaja S, Venkataramanaiah M. Outcome of varicocelectomy with different degrees of clinical varicocele in infertile male. Advances in Andrology. 2015; 2:5-9. 26. Camargo M, Montani DA, Gozzo FC, et al. Lipid fingerprinting profile of seminal plasma of patients perfomingsubinguinal micro- surgery of varicocelectomy. Fertil Steril. 2012; 98:S146-S147. 27. Cooper TG, Weidner W, Nieschlag E. The influence of inflam- mation of the human male genital tract on secretion of the seminal markers α-glucosidase, glycerophosphocholine, carnitine, fructose and citric acid. Int J Androl. 1990; 13:329-336. 28. Mieusset R, Bieth E, Daudin M, et al. Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non-azoospermic. Andrology. 2020; 8:645-653. Correspondence Ahmed Fathy Aboseif, MD ahmed.Fathy.mohamed@med.bsu.edu.eg Nashaat Nabil, MD nashaatnabil70@gmail.com Andrology & STDs Department, Beni Suef Faculty of Medicine, Beni Suef University, Beni Suef, Egypt Sameh Fayek GamalEl Din, MD (Corresponding Author) samehfayek@kasralainy.edu.eg Ahmad Zaghloul, MD ahmadzag@kasralainy.edu.eg Andrology & STDs Department, Kasr Alainy Faculty of Medicine, Cairo University, Cairo, Egypt Amgad Elseginy, MD amgad_elseginy@yahoo.com Shaimaa Ali Abdelkareem, MD shaimaaali170@yahoo.com Clinical Pathology Department, Beni Suef Faculty of Medicine, Beni Suef University, Beni Suef, Egypt Aya Ahmed Onsi, MMBcH aya.onsi@hotmail.com Egypt Ministry of Health & Population, Cairo, Egypt