6 Original article Relation of color Doppler parameters with testicular size in oligoasthenoteratozoospermic men with a varicocele Emad A. Taha a, Saad R. Abd El-Wahed b and Taymour Mostafa c a Department of Dermatology and Andrology, Faculty of Medicine, Assiut University, b Department of Radiology, Faculty of Medicine, Al-Azhar University, Assiut and c Department of Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo, Egypt Correspondence to Taymour Mostafa, MD, Department of Andrology and Sexology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt Tel: + 2 01005150297; fax: + 2 23654133; e-mail: taymour1155@link.net Received 9 November 2011 Accepted 28 December 2011 Human Andrology 2012, 2:6 11 Purpose To assess the relation of color Doppler ultrasound (CDU) parameters with testicular size in oligoasthenoteratozoospermic (OAT) men with a varicocele (Vx). Patients and methods In all, 500 OAT men were investigated: men without Vx (n = 100), men with left-sided Vx (n = 150), and men with bilateral Vx (n = 250). They were subjected to history taking, clinical evaluation, and scrotal CDU examination. Results There was a significant decrease in testicular sizes and a significant increase in size discrepancy in OAT men with left-sided and bilateral Vx compared with OAT men without Vx. Maximum vein diameter, vein numbers, and venous reflux duration of OAT men with bilateral Vx demonstrated a significant increase compared with OAT men with left-sided Vx and OAT men without Vx. Maximum vein diameter, vein numbers, and venous reflux duration in OAT men with left-sided Vx demonstrated a significant increase compared with OAT men without Vx. Maximum vein diameter on the left side demonstrated significant negative correlations with ipsilateral testicular size, right testis size, and total testicular size and a significant positive correlation with size discrepancy. CDU parameters were associated with significant decreased total testicular size in OAT men with bilateral Vx and increased size discrepancy in OAT men with left-sided Vx. Conclusion Vx is associated with a significant decrease in ipsilateral, total testicular size, and increased size discrepancy. CDU parameters were associated with a significant decrease in total testicular size in OAT men with bilateral Vx and a significant increase in size discrepancy in OAT men with left-sided Vx. Keywords: color Doppler ultrasound, male infertility, oligoasthenoteratozoopsermia, testis, varicocele Hum Androl 2:6 11 & 2012 Human Andrology 2090-6048 Introduction Varicocele (Vx) prevalence is approximately 15% in postpubertal populations, with the prevalence in infertility clinics approaching 40%. Vx may be associated with a variety of spermatogenetic conditions, ranging from normal semen parameters to moderate oligoasthenoteratozoospermia or azoospermia [1 3]. Its effect on spermatogenesis in infertile men is often reflected by a low sperm count, decreased sperm motility, and/or increased abnormal morphology being proportionate to its clinical grade [4,5]. Vx is often accompanied by testicular growth arrest and reduced volume [6 8]. Reduced testicular volume means fewer tubules and thus also a lower number of germ cells [9]. A discrepancy between the sizes of two testes secondary to Vx has been demonstrated in different studies [10,11]. Testicular size was demonstrated to be an important prognostic factor for the outcome of Vx surgery [12,13]. Most studies on the effect of Vx on testicular size depended on clinical grading and little has been published on color Doppler ultrasound (CDU) parameters on testicular size and/or asymmetry [14,15]. Stahl and Schlegel [16] concluded that physical examination is limited by intraobserver and interobserver bias and standardized criteria for the ultrasonographic diagnosis of Vx do not exist recommending that Vx grade and venous diameter measured on ultrasound are prognostically useful parameters. This study aimed to assess the relation of color Doppler parameters with testicular size in infertile men with a Vx. Patients and methods In all, 500 infertile oligoasthenoteratozoospermic (OAT) men were included in this study, recruited from the University Hospital after institutional review board 2090-6048 & 2012 Human Andrology DOI: 10.1097/01.XHA.0000410960.01356.5e
Relation of color Doppler parameters with testicular size Taha et al. 7 Table 1 Characteristic data of the studied groups (mean, SD) Infertile men without Vx (n = 100) Infertile men with left-vx (n = 150) Infertile men with bilateral Vx (n = 250) Age (years) 29.1 ± 4.6 30.0 ± 6.46 34.1 ± 6.5 Sperm count (10 6 /ml) 11.1 ± 3.26 10.9 ± 3.4 10.22 ± 3.47 Sperm motility (%) 22.1 ± 2.84 19.87 ± 7.35 18.36 ± 8.6 Sperm abnormal forms (%) 40.8 ± 4.8 41.03 ± 4.99 42.44 ± 5.03 Left testicular size (ml) 17.9 ± 2.3 13.1 ± 2.3 a 10.2 ± 1.9 a,b Left vein number (n) 1.97 ± 0.7 3.47 ± 1.06 a 4.12 ± 1.1 a,b Left maximum vein diameter (mm) 1.79 ± 0.54 3.86 ± 0.72 a 4.42 ± 0.97 a,b Left venous reflux (m/s) 1.78 ± 0.87 3.96 ± 0.11 a 3.94 ± 0.16 a Right testicular size (ml) 17.86 ± 1.78 15.4 ± 2.5 12.1 ± 1.9 a,b Right vein number (n) 1.35 ± 0.58 1.67 ± 0.75 3.0 ± 0.8 a,b Right maximum vein diameter (mm) 1.4 ± 0.45 1.71 ± 0.5 3.13 ± 0.5 a,b Right venous reflux (m/s) 1.59 ± 0.97 1.59 ± 0.92 3.76 ± 0.5 a,b Total testicular sizes (ml) 35.55 ± 3.93 27.4 ± 3.8 a 20.3 ± 3.7 a,b Testicular size difference (ml) 0.75 ± 1.77 a,b 2.44 ± 1.3 a 1.7 ± 1.1 a,b Vx, varicocele. a Significant difference from that of infertile men without Vx (Po0.05). b Significant difference from that of infertile men with left Vx (Po0.05). approval and informed consent: OAT men without Vx (n = 100), OAT men with left-sided Vx (n = 150), and OAT men with bilateral Vx (n = 250). The exclusion criteria were orchitis, undescended testis, idiopathic testicular atrophy, hypogonadism, and subclinical Vx. All patients were subjected to history taking, clinical examination, scrotal CDU examination, and semen analysis according to WHO guidelines [17]. Color Doppler scrotal ultrasound was carried out by the second author, a specialized radiologist, using a 7.5 MHz high-resolution linear array transducer (Sonoline Versa plus, Seimens Medical System, Erlangen, Bavaria, Germany) with pulsed and color Doppler capabilities. On gray-scale sonography, the presence of any paratesticular anechoic, tortuous tubular structures or widened spermatic veins were noted. The testis was examined for its size, echogenicity as well as perfusion. Testicular size (ml) was automatically calculated by (length anteroposterior transverse dimensions 0.52). Then, the patient was examined in the standing position. Color mode was used for the evaluation of testicular veins before, at, and after the Valsalva maneuver both for size and reflux. Reflux, whether Valsalva-induced or spontaneous, was considered abnormal if lasted more than 1s. The maximum vein diameter was determined during the Valsalva maneuver, where spectral analysis was used to detect reflux duration [18]. Statistical analysis The data were analyzed and expressed as mean ± SD, using Statistical Package for the Social Sciences (SPSS) program version 17 (SPSS Inc., Chicago, Illinois, USA). Unpaired t-test and Mann Whitney test were used to compare parametric and nonparametric variables between groups. Pearson s correlation test was applied to analyze correlations between numeric variables. Statistical significance was set at P less than 0.05. Results Infertile OAT men without Vx had significantly higher right testicular, left testicular, and total testicular size and lower testicular size difference compared with OAT men with left-sided Vx and OAT men with bilateral Vx. OAT men with bilateral Vx had significantly lower right testicular, left testicular, total testicular size, and higher testicular size difference compared with OAT men without Vx. Maximum vein diameter, vein numbers, and venous reflux duration of OAT men with bilateral Vx demonstrated a significant increase compared with OAT men with leftsided Vx and OAT men without Vx (Table 1). Maximum vein diameter on left side demonstrated significant negative correlations with ipsilateral testicular size, right testis size, total testicular size, sperm count, sperm motility and significant positive correlation with size discrepancy, sperm abnormal forms in both unilateral and bilateral Vx groups. Sperm count, sperm motility, and significant positive correlation with size discrepancy, sperm abnormal forms. CDU parameters were associated with significant decreased total testicular size in OAT men with bilateral Vx and increased size discrepancy in OAT men with left-sided Vx (Table 2, Figs 1 7). Discussion In this study, the presence of Vx in infertile OAT, whether unilateral or bilateral, was associated with a significant decrease in total, ipsilateral, and contralateral testicular size compared with OAT men without a Vx. Decreased testicular size was correlated significantly negatively with CDU parameters of ipsilateral and contralateral Vx, especially maximum vein diameter and reflux duration. In their study, Lipshultz and Corriere [9] observed progressive testicular hypotrophy in patients with Vx on comparing healthy volunteers in their early 20s with patients with a mean age of 30 years. A maximum of 50% of infertile patients with a unilateral Vx were reported to have ipsilateral testicular hypotrophy [19]. Sakamoto et al. [20] added that left clinical testicular Vx is associated with relative ipsilateral testicular hypotrophy in infertile patients. In addition, different researchers have demonstrated decreased testicular size in Vx-associated cases, especially the affected side [21 24]. CDU is a noninvasive diagnostic method to evaluate Vx, the size of the pampiniform plexus, and blood flow
Table 2 Correlations of tested parameters Age Right testis size Right vein number Right maximum V.D Right vein refux Left testis size Left vein number Left maximum V.D Left vein reflux Testis size difference Right testis size 0.435* 0.000 Right vein number 0.377* 0.681* 0.000 0.000 Right maximum V.D 0.368* 0.682* 0.781* 0.000 0.000 0.000 Right vein reflux 0.202* 0.567* 0.738* 0.775* 0.000 0.000 0.000 0.000 Left testis size 0.348* 0.859* 0.612* 0.640* 0.561* 0.000 0.000 0.000 0.000 0.000 Left number 0.186* 0.427* 0.590* 0.579* 0.512* 0.596* 0.000 0.000 0.000 0.000 0.000 0.000 Left maximum V.D 0.213* 0.461* 0.543* 0.630* 0.482* 0.615* 0.714* 0.000 0.000 0.000 0.000 0.000 0.000 0.000 Left vein reflux 0.139* 0.434* 0.481* 0.474* 0.478* 0.648* 0.626* 0.734* 0.002 0.000 0.000 0.000 0.000 0.000 0.000 0.000 Testis size difference 0.010 0.251* 0.035 0.039 0.049 0.240* 0.241* 0.240* 0.352* 0.844 0.000 0.472 0.431 0.317 0.000 0.000 0.000 0.000 Tetsis size sum 0.405* 0.962* 0.670* 0.684* 0.585* 0.966* 0.533* 0.561* 0.565* 0.006 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.902 Sperm count 0.035 0.070 0.048 0.264* 0.091 0.066 0.242* 0.508* 0.061 0.007 0.069 0.461 0.140 0.307 0.000 0.053 0.162 0.000 0.000 0.197 0.881 0.147 Sperm motility 0.065 0.076 0.075 0.123* 0.087 0.075 0.040 0.550* 0.095* 0.005 0.075 0.137* 0.169 0.109 0.113 0.009 0.065 0.113 0.399 0.000 0.000 0.909 0.111 0.004 Sperm abnormal 0.022 0.074 0.140* 0.136* 0.135* 0.068 0.119* 0.135* 0.088 0.013 0.071 0.115* 0.280 forms 0.640 0.118 0.003 0.004 0.004 0.152 0.011 0.004 0.062 0.782 0.135 0.014 0.000 VD, vein diameter. *Correlation is significant at the 0.001 level (two-tailed). Testis size sum Sperm count Sperm motility 8 Human Andrology
Relation of color Doppler parameters with testicular size Taha et al. 9 Figure 1 Figure 3 25.00 20.00 8.00 Lt testis size (ml) 15.00 Testis size difference (ml) 4.00 5.00 0.00 0.00 Ltmax vein diameter (mm) Lt max vein diameter (mm) Lt testis size. testis size difference. Figure 2 Figure 4 25.00 50.00 20.00 40.00 Rt testis size (ml) 15.00 Testis sizes sum (ml) 30.00 20.00 5.00 Lt max vein diameter (mm) Lt max vein diameter (mm) right (Rt) testis size. sum of testis sizes. parameters of the spermatic veins [25]. It was shown that if venous pressure alone increased as in Vx, a reflex increase occurred in the pre-capillary resistance, with diminished testicular blood flow comprising the nutrient supply of the affected organ [26]. In this work, the left maximum vein diameter was demonstrated to correlate significantly negatively with testis sizes, sum of the sizes, sperm count, and sperm motility and demonstrated a significant positive correlation with size discrepancy and percentage of abnormal forms of sperm. The first study that showed the negative influence of a Vx on testicular size with ultrasoundderived measurements was performed by Zini et al. [27]. Later, Zini et al. [10] confirmed the loss of left testicular size in infertile men with left Vx, mentioning that the degree of left testicular hypotrophy was proportional to Vx grade and maximum internal spermatic vein diameters, with no report on the effect of reflux duration or number of veins. Diamond et al. [28] added that sonographically derived size differentials greater than 10% between normal and affected testes correlated with significantly decreased semen parameters. In addition, grade III Vx was demonstrated to have a greater number of large veins compared with grade I Vx [29]. Shindel et al. [30] reported that the number of veins ligated in Vx repair was correlated positively with an increase in total sperm motility, where the repair of grade II Vx was associated with a significantly greater increase in normal sperm morphology than did the repair of grade I or III Vx.
10 Human Andrology Figure 5 Figure 7 Testicular volume assessment by grey mode scrotal us. Varicocele picture showing venous reflux on color mode scrotal us. It is concluded that Vx is associated with a significant decrease in ipsilateral, total testicular size, and increased size discrepancy. CDU parameters were associated with a significant decrease in total testicular size in infertile men with bilateral Vx and a significant increase in size discrepancy in infertile men with left-sided Vx. Figure 6 Acknowledgements Conflicts of interest There are no conflicts of interest. Dilated veins in left varicocele by grey mode scrotal us. Patel and Sigman [14] found that the prevalence of testicular size discrepancy was associated with Vx grade, with higher Vx grades having a higher prevalence of testicular size discrepancy (the prevalence of testicular size discrepancy in large, medium, small, and no Vx groups (60.9, 30.8, 19.9, and 13.2%, respectively). Recently, Hassan et al. [31], in their study on 124 cases, concluded that there are significant decreases in testicular size, testicular perfusion, blood velocity, and testicular artery diameter in infertile men with Vx. References 1 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; 41:125 129. 2 Sadek A, Almohamdy ASA, Zaki A, Aref M, Ibrahim SM, Mostafa T. Sperm chromatin condensation in infertile men with varicocele before and after surgical repair. Fertil Steril 2011; 95:1705 1708. 3 Zalata A, El Mogy M, Abdel Khabir A, El Bayoumy Y, El Baz M, Mostafa T. Sperm caspase-9 in oligoasthenoteratozoospermic men with and without varicocele. Fertil Steril 2011; 96:1097 1099. 4 Aziz MTA, Mostafa T, Atta H, Kamal O, Kamel M, Hosni H, et al. Heme oxygenase enzyme activity in seminal plasma of oligoasthenoteratozoospermic males with varicocele. Andrologia 2010; 42:236 241. 5 Mohamad Al Ali B, Marszalek M, Shamloul R, Pummer K, Trummer H. Clinical parameters and semen analysis in 716 Austrian patients with varicocele. Urology 2010; 75:1069 1073. 6 Haans LCF, Laven JSE, WPTM Mali, Te Velde ER, Wensing CJG. Testis volumes, semen quality and hormonal patterns in adolescents with and without a varicocele. Fertil Steril 1991; 56:731 736. 7 Aragona F, Ragazzi R, Pozzan GB, De Caro R, Munari PF, Milani C, et al. Correlation of testicular volume, histology and LHRH test in adolescents with idiopathic varicocele. Eur Urol 1994; 26:61 66. 8 Sayfan J, Siplovich L, Koltun L, Benyamin N. Varicocele treatment in pubertal boys prevents testicular growth arrest. J Urol 1997; 157:1456 1457. 9 Lipshultz LI, Corriere JN. Jr. Progressive testicular atrophy in the varicocele patient. J Urol 1977; 117:175 176. 10 Zini A, Buckspan M, Berardinucci D, Jarvi K. Loss of left testicular volume in men with clinical left varicocele: correlation with grade of varicocele. Arch Androl 1998; 41:37 41. 11 Taha EA, Abdel Wahed SR, Mostafa T. Varicocele impact on testicular size of infertile men in unilateral or bilateral associated cases. Hum Androl 2011; 1:76 78. 12 Marks JL, McMahon R, Lipshultz LI. Predictive parameters of successful varicocele repair. J Urol 1986; 136:609 612. 13 Zucchi A, Mearini L, Mearini E, Fioretti F, Bini V, Porena M. Varicocele and fertility: Relationship between testicular volume and seminal parameters before and after treatment. J Androl 2006; 27:548 551. 14 Patel SR, Sigman M. Prevalence of testicular size discrepancy in infertile men with and without varicoceles. Urology 2010; 75:566 568. 15 Poon SA, Gjertson CK, Mercado MA, Raimondi PM, Kozakowski KA, Glassberg KI. Testicular asymmetry and adolescent varicoceles managed expectantly. J Urol 2010; 183:731 734.
Relation of color Doppler parameters with testicular size Taha et al. 11 16 Stahl P, Schlegel PN. Standardization and documentation of varicocele evaluation. Curr Opin Urol 2011; 21:500 505. 17 World Health Organization (WHO). WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999. 18 Trum JW, Gubler FM, Laan R, Van Der Veen F. The value of palpation, varicoscreen contact thermography and colour Doppler ultrasound in the diagnosis of varicocele. Hum Reprod 1996; 11:1232 1235. 19 Sigman M, Jarow JP. Ipsilateral testicular hypotrophy is associated with decreased sperm counts in infertile men with varicoceles. J Urol 1997; 158:605 607. 20 Sakamoto H, Ogawa Y, Yoshida H. Relationship between testicular volume and varicocele in patients with infertility. Urology 2008; 71:104 109. 21 Kass EJ, Belman AB. Reversal of testicular growth failure by varicocele ligation. J Urol 1987; 137:475 476. 22 Jarow JP, Ogle SR, Eskew LA. Seminal improvement following repair of ultrasound detected subclinical varicoceles. J Urol 1996; 155: 1287 1290. 23 Pasqualotto FF, Lucon AM, De Góes PM, Sobreiro BP, Hallak J, Pasqualotto EB, et al. Semen profile, testicular volume and hormonal levels in infertile patients with varicoceles compared with fertile men with and without varicoceles. Fertil Steril 2005; 83:74 77. 24 Sakamoto H, Saito K, Ogawa Y, Yoshida H. Effects of varicocele repair in adults on ultrasonographically determined testicular volume and on semen profile. Urology 2008; 71:485 489. 25 Liguori G, Trombetta C, Garaffa G, Bucci S, Gattuccio I, Salamè L, et al. Color Doppler ultrasound investigation of varicocele. World J Urol 2004; 22:378 381. 26 Sweeney TE, Rozum JS, Gore RW. Alteration of testicular microvascular pressures during venous pressure elevation. Am J Physiol Heart Circ Physiol 1995; 269:H37 H45. 27 Zini A, Buckspan M, Berardinucci D, Jarvi K. The influence of clinical and subclinical varicocele on testicular volume. Fertil Steril 1997; 68:671 674. 28 Diamond DA, Zurakowski D, Bauer SB, Borer JG, Peters CA, Cilento BG. Jr, et al. Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urol 2007; 178 (4 Suppl): 1584 1588. 29 Belani JS, Yan Y, Naughton CK. Does varicocele grade predict vein number and size at microsurgical subinguinal repair? Urology 2004; 64:137 139. 30 Shindel AW, Yan Y, Naughton CK. Does the number and size of veins ligated at left-sided microsurgical subinguinal varicocelectomy affect semen analysis outcomes? Urology 2007; 69:1176 1180. 31 Hassan A, Gad HM, Mostafa T. Radiologically assessed testicular changes in infertile males with varicocele. Andrologia 2011; 43:307 311.