Hendin et al., 1999 (USA) (4949 Hendin BN, Kolettis PN, Sharma RK, Thomas AJ, Jr., Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol. 1999;161:1831-4.) |
Seminal ROS by chemiluminescence with luminol; seminal TAC by enhanced chemiluminescence |
17 normozoospermic men without varicocele; 15 men with incidental varicocele; 21 infertile men with palpable varicocele |
ROS levels: Controls: 1.3 ± 0.33 log[ROS+1] Men with incidental varicocele: 1.99 ± 0.26 log[ROS+1] (P<0.05 versus controls); Infertile men with varicocele:2.18 ± 0.25 log[ROS+1] (P<0.05 versus controls); TAC: Controls: 1443.0 ± 105.0 molar Trolox; Men with incidental varicocele: 939.0 ± 107.0 molar Trolox (P<0.05 versus controls); Infertile men with varicocele: 1186.0 ± 96.9 molar Trolox (P<0.05 versus controls) |
Sharma et al., 1999 (USA) (4343 Sharma RK, Pasqualotto FF, Nelson DR, Thomas AJ, Jr., Agarwal A. The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility. Hum Reprod. 1999;14:2801-7.) |
Seminal ROS by chemiluminescence with luminol; seminal TAC by enhanced chemiluminescence |
25 normozoospermic fertile, healthy men; 55 infertile men with palpable varicocele |
ROS levels: Controls: 1.39 ± 0.73 log[ROS+1]; Infertile men with varicocele: 2.10 ± 1.21 log[ROS+1] (P<0.05 versus controls) TAC: Controls: 1650.93 ± 532.22 molar Trolox; Infertile men with varicocele: 1100.11 ± 410.13 molar Trolox (P<0.05 versus controls) |
Köksal et al., 2000 (Turkey) (5656 Köksal IT, Tefekli A, Usta M, Erol H, Abbasoglu S, Kadioglu A. The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU international. 2000;86:549-52.) |
Intratesticular MDA by thiobarbituric acid reaction |
10 infertile men without varicocele; 15 infertile men with palpable varicocele |
MDA levels: Infertile men without varicocele: 33.5 ± 18.93 pmol/mg; Infertile men with varicocele: 38.3 ± 22.92 pmol/mg (P NS versus controls); MDA levels in men with grade III varicocele were higher than in men with lower grade varicocele (P<0.05) |
Pasqualotto et al., 2000 (USA) (4040 Pasqualotto FF, Sharma RK, Nelson DR, Thomas AJ, Agarwal A. Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertility and sterility. 2000;73:459-64.) |
Seminal ROS by chemiluminescence with luminol; Seminal TAC by enhanced chemiluminescence |
19 normozoospermic men without varicocele; 77 infertile men with palpable varicocele |
ROS levels: Controls: 1.3 ± 0.3 log[ROS+1]; Infertile men with varicocele: 2.2 ± 0.13 log[ROS+1] (P<0.05 versus controls) TAC: Controls: 1653.98 ± 115.29 molar Trolox; Infertile men with varicocele: 1173.05 ± 58.07 molar Trolox (P<0.05 versus controls) |
Saleh et al., 2003 (USA) (4444 Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC, Thomas AJ, Jr. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertility and sterility. 2003;80:1431-6.) |
Seminal ROS by chemiluminescence with luminol; Seminal TAC by enhanced chemiluminescence |
16 fertile men without varicocele; 15 infertile men without varicocele; 16 infertile men with palpable varicocele |
ROS levels: Controls: 0.36 (IQR: 0.1, 2) (cpm)/20×106 sperm/mL; Infertile men without varicocele: 1.7 (IQR: 0.1, 5.4) (cpm)/20×106 sperm/mL (P NS versus controls); Infertile men with varicocele: 12 (IQR: 1.3, 53.4) (cpm)/20×106 sperm/mL (P<0.05 versus controls) TAC: Controls: 871 (IQR: 699, 1288) molar Trolox; Infertile men without varicocele: 904 (IQR: 693, 978) molar Trolox (P NS versus controls); Infertile men with varicocele: 693 (IQR: 499, 822) molar Trolox (P<0.05 versus controls) |
Allamaneni et al., 2004 (USA) (5757 Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ, Jr., Agarwal A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertility and sterility. 2004;82:1684-6.) |
Seminal ROS by chemiluminescence with luminol; Seminal TAC by enhanced chemiluminescence |
46 infertile men with palpable left varicocele |
Median ROS level 119 (13, 2475) x104cpm ROS levels positively correlated with varicocele grade |
Mehraban et al., 2005 (Iran) (3737 Mehraban D, Ansari M, Keyhan H, Sedighi Gilani M, Naderi G, Esfehani F. Comparison of nitric oxide concentration in seminal fluid between infertile patients with and without varicocele and normal fertile men. Urology journal. 2005;2:106-10.) |
Seminal total nitrite and nitrate levels |
40 fertile men without varicocele; 40 infertile men without varicocele; 40 infertile men with palpable varicocele |
Seminal total nitrite and nitrate levels: Controls: 37.06 ± 20.39 μmol/L; Infertile men without varicocele: 33.7 ± 18.99 μmol/L (P NS versus controls); Infertile men with varicocele: 52.34 ± 26.62 μmol/L (P<0.05 versus controls and infertile men without varicocele) |
Smith et al., 2006 (Chile) (9898 Smith R, Kaune H, Parodi D, Madariaga M, Rios R, Morales I, et al. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2006;21:986-93.) |
Seminal ROS by chemiluminescence with luminol; Seminal TAC by enhanced chemiluminescence |
25 normozoospermic healthy donors 37 men with varicocele and normal SA; 18 men with varicocele and abnormal SA |
ROS levels: Controls: 2.8 ± 0.9 log[ROS+1]; Men with varicocele and normal SA: 3.3 ± 1.2 log[ROS+1] (P<0.05 versus controls); Men with varicocele and abnormal SA: 4.3 ± 1.1 log[ROS+1] (P<0.05 versus controls) TAC: Controls: 1.2 ± 0.1 mM Trolox; Men with varicocele and normal SA: 1.1 ± 0.4 mM Trolox (P NS versus controls); Men with varicocele and abnormal SA: 1.1 ± 0.5 mM Trolox (P NS versus controls) |
Ishikawa et al. 2007 (Japan) (5858 Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Increased testicular 8-hydroxy-2'-deoxyguanosine in patients with varicocele. BJU international. 2007;100:863-6.) |
Intratesticular 8-OHdG positive cell by immunostaining |
5 healthy fertile men; 36 infertile men with palpable varicocele and abnormal SA |
Incidence of 8-OHdG immunostained germ cells: Controls: 29 ± 5.4%; Varicocele grade I:38 ±10%, (P<0.05 versus controls); Varicocele grade II: 41 ± 9.1% (P<0.05 versus controls); Varicocele grade III: 57 ± 9.3% (P<0.05 versus controls and grade I+II) |
Sakamoto et al., 2008 (Japan) (3838 Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU international. 2008;101:1547-52.) |
Seminal NO levels; Seminal 8-OHdG levels; Seminal SOD activity |
15 normozoospermic men without varicocele; 15 infertile men with varicocele and normal SA; 15 infertile men with palpable varicocele and oligozoospermia |
NO levels: Controls: 8.2 ± 4.3μmol/L; Men with varicocele and normal SA:15.4 ± 0.3μmol/L (P<0.05 versus controls); Men with varicocele and oligozoospermia: 7.8 ± 4.0 μmol/L (P NS versus controls); 8-OHdG levels: Controls: 14.7 ± 8.3 μmol/L; Men with varicocele and normal SA:10.0 ± 5.4 μmol/L (P NS versus controls); Men with varicocele and oligozoospermia: 10.8 ± 7.5 μmol/L (P NS versus controls); SOD activity: Controls: 75.6 ± 13.1%; Men with varicocele and normal SA: 84 ± 6.7% (P<0.05 versus controls); Men with varicocele and oligozoospermia: 89.4 ± 4.4 % (P<0.05 versus controls) |
Mostafa et al., 2009 (Egypt) (4747 Mostafa T, Anis T, Imam H, El-Nashar AR, Osman IA. Seminal reactive oxygen species-antioxidant relationship in fertile males with and without varicocele. Andrologia. 2009;41:125-9.) |
Seminal MDA by thiobarbituric acid reaction; Seminal H2O2 by spectrophotometric Method; Seminal SOD; Seminal GPx; Seminal Cat |
45 fertile men without varicocele; 45 fertile men with varicocele; 42 infertile men with unilateral palpable varicocele and abnormal SA; 44 infertile men with abnormal SA and without varicocele |
MDA and H2O2 were significantly higher, and antioxidants were significantly lower in fertile men with varicocele, OA men with and without varicocele compared with controls; All ROS parameters were increased, and all antioxidants were decreased in infertile men with varicocele compared to infertile men without varicocele |
Abd-Elmoaty et al., 2010 (Egypt) (6262 Abd-Elmoaty MA, Saleh R, Sharma R, Agarwal A. Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele. Fertility and sterility. 2010;94:1531-4.) |
Seminal NO levels by colorimetric method; Seminal MDA by colorimetric method; Seminal SOD; Seminal GPx; Seminal Cat |
18 fertile men without varicocele; 42 infertile men with varicocele |
MDA levels: Controls: 8.4 ± 1.3 pmol/mL; Infertile men with varicocele: 13.5 ± 2.8 pmol/mL (P<0.05 versus controls) NO levels: Controls: 11.3 ± 1.0 nmol/L; Infertile men with varicocele: 17.9 ± 4.1 nmol/L (P<0.05 versus controls); CAT, SOD, GPX, and ascorbic acid were significantly lower in infertile men with varicocele compared with fertile men (P values <.05, .01, .01, and .05, respectively) |
Blumer et al., 2011 (Brazil) (165165 Blumer CG, Restelli AE, Giudice PT, Soler TB, Fraietta R, Nichi M, et al. Effect of varicocele on sperm function and semen oxidative stress. BJU international. 2012;109:259-65.) |
Seminal MDA by thiobarbituric acid reaction |
19 men without varicocele; 12 men with varicocele (fertility status not informed); |
MDA levels: Controls: 301.4 ± 95.9 ng/mL Men with varicoceles: 287.1 ± 127.7 ng/mL (P NS versus controls) |
Mostafa et al., 2012 (Egypt) (5959 Mostafa T, Anis T, El Nashar A, Imam H, Osman I. Seminal plasma reactive oxygen species-antioxidants relationship with varicocele grade. Andrologia. 2012;44:66-9.) |
Seminal MDA by thiobarbituric acid reaction; Seminal H2O2 by spectrophotometric Method; Seminal SOD; Seminal GPx; Seminal Cat |
20 fertile men without varicocele; 22 infertile men with grade 1varicocele; 43 infertile men with grade II varicocele; 23 infertile men with grade III varicocele |
Levels of MDA and H2O2 were increased and antioxidants; SOD, Cat, GPx, vit. C levels were decreased in men with varicocele of all grades (I, II, III) compared with the controls; Men with grade II and III varicocele demonstrated higher MDA and H2O2 levels as well as decreased activities of SOD, Cat, GPx, and levels of vit. C compared with men with grade I varicocele. |
Mostafa et al., 2016 (Egypt) (5050 Mostafa T, Rashed L, Taymour M. Seminal cyclooxygenase relationship with oxidative stress in infertile oligoasthenoteratozoospermic men with varicocele. Andrologia. 2016;48(2):137-42.) |
Seminal MDA by thiobarbituric acid reaction; Seminal GPx |
24 fertile men without varicocele; 22 fertile men with varicocele; 34 infertile men with palpable varicocele and abnormal SA; 24 infertile men with abnormal SA and without varicocele |
MDA levels: Controls: 1.2 ± 0.17 nmol/mL; Fertile men with varicocele: 1.9 ± 0.69 nmol/mL (P<0.05 versus controls); Infertile men without varicocele and abnormal SA: 2.4 ± 0.47 nmol/mL (P<0.05 versus controls and other groups); Infertile men with varicocele and abnormal SA: 3.02 ± 0.47 nmol/mL (P<0.05 versus controls and other groups) GPx activity: Controls: 0.47 ± 0.6 U/mL; Fertile men with varicocele: 0.36 ± 0.8 U/mL (P<0.05 versus controls); Infertile men without varicocele and abnormal SA: 0.3 ± 0.03 U/mL (P<0.05 versus controls and other groups); Infertile men with varicocele and abnormal SA: 0.21 ± 0.04 U/mL (P<0.05 versus controls and other groups) |
Ni et al., 2016 (China) (6161 Ni K, Steger K, Yang H, Wang H, Hu K, Zhang T, et al. A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno/oligozoospermic clinical varicocoele. Andrology. 2016;4:816-24.) |
Seminal MDA by thiobarbituric acid reaction |
25 healthy normozoospermic men without varicocele; 15 infertile men with subclinical varicocele; 19 infertile men with grade I varicocele; 18 infertile men with grade II varicocele; 14 infertile men with grade III varicocele |
MDA levels: Control group: 7.45 ± 3.58 nmol/mL; Varicocele subclinical group: 7.22 ± 3.33 nmol/mL; Varicocele grade I group: 12.18 ± 4.86 nmol/mL (P<0.05 versus controls); Varicocele grade II group: 14.12 ± 5.42 nmol/mL (P<0.05 versus controls); Varicocele grade III group: 15.86 ± 6.78 nmol/mL (P<0.05 versus controls) |
Abdelbaki et al., 2017 (Egypt) (4242 Abdelbaki SA, Sabry JH, Al-Adl AM, Sabry HH. The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: A prospective controlled study. Arab journal of urology. 2017;15:131-9.) |
Seminal ROS by chemiluminescence with luminol; Seminal TAC by Colorimetric assay kit |
20 normozoospermic fertile men without varicocele; 60 infertile men with palpable varicocele |
ROS levels: Controls: 2.62 ± 0.8 log[ROS+1]; Infertile men with varicocele: 4.49 ± 0.9 log[ROS+1] (P<0.05 versus controls); TAC: Controls: 1.5 ± 0.5 mM Trolox; Infertile men with varicocele: 0.97 ± 0.4 mM Trolox (P<0.05 versus controls) |
Alkan et al., 2018 (Turkey) (6060 Alkan İ, Yüksel M, Canat HL, Atalay HA, Can O, Özveri H, et al. Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters. World J Mens Health. 2018;36:255-62.) |
Seminal ROS by chemiluminescence with luminol; Seminal superoxide anion by chemiluminescence with lucigenin |
13 normozoospermic men without varicocele; 17 men with grade II varicocele; 17 men with grade III varicocele |
ROS levels: Controls: 2.4 ± 0.1 log[ROS+1]; Men with grade II varicocele: 2.7 ± 0.4 log[ROS+1] (P<0.05 versus controls); Men with grade III varicocele: 3.2 ± 0.5 log[ROS+1] (P<0.05 versus controls and grade II group); Superoxide anion levels: Controls: 2.3 ± 0.2 log[ROS+1]; Men with grade II varicocele: 2.5 ± 0.3 log[ROS+1] (P<0.05 versus controls); Men with grade III varicocele: 3.0 ± 0.5 log[ROS+1] (P<0.05 versus controls and grade II group) |
Tanaka et al., 2020 (Japan) (4545 Tanaka T, Kobori Y, Terai K, Inoue Y, Osaka A, Yoshikawa N, et al. Seminal oxidation-reduction potential and sperm DNA fragmentation index increase among infertile men with varicocele. Human fertility (Cambridge, England). 2022;25:142-6.) |
Seminal ORP measured by MiOXSYS |
102 normozoospermic men without varicocele; 138 infertile men with palpable varicocele |
ORP: Men without varicocele: 9.82 ± 10.31 mV/106 sperm/mL; Infertile men with varicocele: 16.73 ± 12.13 mV/106 sperm/mL (P<0.05 versus controls) |
Ammar et al., 2021 (Tunisia) (5151 Ammar O, Tekeya O, Hannachi I, Sallem A, Haouas Z, Mehdi M. Increased Sperm DNA Fragmentation in Infertile Men with Varicocele: Relationship with Apoptosis, Seminal Oxidative Stress, and Spermatic Parameters. Reprod Sci. 2021;28:909-19.) |
Seminal MDA by thiobarbituric acid reaction; Seminal SOD; Seminal Cat; Seminal GPx |
29 fertile men without varicocele; 11 infertile men with palpable varicocele and normal SA; 40 infertile men with palpable varicocele and abnormal SA |
MDA levels: Controls: 0.56 ± 0.25 nmol/mL; Infertile men with varicocele and normal SA: 1.43 ± 1.2 nmol/mL (P<0.05 versus controls); Infertile men with varicocele and abnormal SA: 1.63 ± 1.38 nmol/mL (P<0.05 versus controls); GPx and CAT activities were decreased in both groups with varicocele, and SOD activity was decreased only in infertile men with varicocele and abnormal SA when compared to controls (P<0.05) |
Camargo et al., 2021 (Brazil) (166166 Camargo M, Ibrahim E, Intasqui P, Belardin LB, Antoniassi MP, Lynne CM, et al. Seminal inflammasome activity in the adult varicocele. Human fertility (Cambridge, England). 2021:1-15.) |
Seminal MDA by thiobarbituric acid reaction |
15 normozoospermic men without varicocele; 15 infertile men with grade 2 or 3 varicocele |
MDA levels: Controls: 20.1 ± 4.59 nmol/mL Infertile men with varicocele: 21.6 ± 8.97 nmol/mL (P NS versus controls) |
Gill et al., 2021 (Poland) (4646 Gill K, Kups M, Harasny P, Machalowski T, Grabowska M, Lukaszuk M, et al. The Negative Impact of Varicocele on Basic Semen Parameters, Sperm Nuclear DNA Dispersion and Oxidation-Reduction Potential in Semen. Int J Environ Res Public Health. 2021;18(11).) |
Seminal ORP measured by MiOXSYS |
105 normozoospermic men without varicocele; 64 men with proven fertility; 71 infertile men with clinical varicocele; 95 infertile men without varicocele |
ORP: Normozoospermic group: 1.68 ± 0.91 mV/106 sperm/mL; Proven fertility group: 1.00 ± 0.8 mV/106 sperm/mL; Varicocele group: 36.10 ± 60.97 mV/106 sperm/mL (P < 0.05 versus normozoospermic and proven fertility); |