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Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele
Journal of Pediatric Surgery (2012) 47, 383–385
www.elsevier.com/locate/jpedsurg
Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele David J.B Keene a,⁎, Yasmin Sajad b , George Rakoczy c , Raimondo M. Cervellione a a
Department of Paediatric Urology, Royal Manchester Children's Hospital, M13 9WL Manchester, United Kingdom Department of Andrology and Fertility, St Mary's Hospital, M13 9WL Manchester, United Kingdom c Department of Paediatric Surgery, Royal Manchester Children's Hospital, M13 9WL Manchester, United Kingdom b
Received 5 November 2011; accepted 10 November 2011
Key words: Semen variables; Adolescent; Varicocele; Testicular volume
Abstract Purpose: Varicocele is potentially a progressive condition that may affect fertility. The authors have encouraged sperm banking for their postpubertal patients with varicocele and aim to evaluate the sperm parameters in this cohort of patients. Methods: With institutional ethical approval, sperm variables (volume, concentration, and forward motility) of patients with postpubertal varicocele who opted for sperm banking were prospectively recorded. The following parameters were also acquired: (a) ultrasound measurement of testicular volume, (b) clinical grade, and (c) venous Doppler. Patients were divided into 2 groups: symmetrical testis (group A) and asymmetrical testis (group B). Testicular asymmetry was defined as greater than 20% difference in testicular volume compared with contralateral testis. Sperm parameters were compared between groups A and B using Mann-Whitney U test and P b .05. Results: Fifteen patients were included: 10 in group A and 5 in group B. Median semen concentration in group B was significantly lower than group A (3 vs 26 million/mL; P = .04). One hundred percent of group B failed World Health Organisation adult criteria for normal spermiograms compared with 50% of group A. Conclusions: Sperm concentration and quality was lower in patients with asymmetrical testis. Testicular dysfunction may be present before the onset of testicular hypotrophy. When testicular hypotrophy is present, testicular dysfunction is very likely. © 2012 Elsevier Inc. All rights reserved.
Idiopathic varicocele is a progressive condition that potentially could cause infertility [1,2]. Current guidelines for adolescents with varicocele focus mainly on the testicular
Presented at the 58th Annual Meeting of the British Association of Paediatric Surgeons, Belfast, Northern Ireland, July 20-22, 2011. ⁎ Corresponding author. Tel.: +44 161 701 2177; fax: +44 161 701 2928. E-mail address: [email protected] (D.J.B. Keene). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2011.11.035
volume as an indicator of testicular damage [3]. It is known that patients with asymmetry testicular volume have worse semen variables at 18 years [2,4] compared with those with symmetrical testes. Since 2009, the authors have been offering sperm banking to all postpubertal adolescents with varicocele. This study aims to compare semen variables in patients with symmetrical testes with those patients with asymmetrical testes in the presence of idiopathic varicocele.
384
1. Methods
D.J.B. Keene et al. Table 1
Demographic details of patients (n = 15) Group A
Ethical approval was obtained for collecting sperm data from adolescent patients with varicocele (REC 09/H1013/15). These data will form the first part of a randomised study of early surgery vs conservative management. Postpubertal adolescents aged 12 to 17 years with clinically evident left idiopathic varicocele [5] underwent the study. The clinical grade of the varicocele was determined according to the Dubin and Amelar classification [5]. Testicular venous Doppler was performed, and only those with spontaneous venous testicular reflux were included [6]. All patients underwent testicular ultrasound with a 5- to 10-MHz linear probe. Measurements of testicular length, width, and height were obtained using electronic callipers. Testicular volume was then estimated using the formula for a prolate ellipsoid (volume in mL = 0.52 × L × W × H) [7]. Testicular asymmetry was defined as a greater than 20% difference in left testicular volume compared with the contralateral testis [2]. All patients were divided into 2 groups: (a) symmetrical testes and (B) asymmetrical testes. Patients were offered sperm banking at the time of the diagnosis before any intervention. Informed written consent was obtained for semen cryopreservation from all patients. If patients were younger than 16 years, then they had to be Gillick competent [8] before considering sperm banking. Those patients who produced a semen sample by masturbation at the authors' andrology laboratory were included in this study. Semen analysis was performed according to World Health Organisation recommendations (World Health Organisation, 1999) after liquefaction for 20 minutes at 37°C, and the following variables were recorded: semen volume (mL), sperm concentration (million/mL), sperm motility (rapid + forward motility %), and normal morphology (%). Sperm freezing was carried out after dilution into a cryoprotectant medium. Statistical analyses were performed using Stats Direct Package version 2.7.1. Data are expressed as median (range) unless otherwise stated. A 2-sided Mann-Whitney U test was used to compare medians between groups A and B. A P value of less than .05 was accepted as being statistically significant.
2. Results Fifteen patients were included in this study. Ten had symmetrical testicular size (group A), and 5 had asymmetrical testicular size (group B). The median testicular volume differential for group A was 6.9% and that for group B was 30%. Table 1 shows patients' age, varicocele clinical grading, Doppler finding, and testicular volume. The semen volume, forward motility, and morphology were not significantly different between the 2 groups
No. of patients Age of patients (y) a
Group B
10 5 15.6 15.9 (14.7-16.1) (12.5-17.3) 0 0
No. of patients with Grade 1 clinical grade [4] (Valsalva) Grade 2 2 (palpable) Grade 3 8 (visible) No. of patients with Grade 1 0 Doppler grade [5] (Valsalva) 2 Grade 2 (spontaneous intermittent) Grade 3 8 (continuous) Testicular volume 6.9 differential b (%) (0-17.3)
1 4 0 2
3 30 (20-60.8)
a Comparison of ages in group A vs group B is not significant (P = .44). b Testicular volume differential = (volume right testis − volume left testis)/volume of right testis × 100.
(Table 2). However, the median semen concentration in group B was significantly lower compared with that in group A (3 vs 26 million/mL; P = .04). All patients in group B failed World Health Organisation adult criteria for normal spermiograms [9] (either sperm concentration b 20 million/mL or forward motility b 50%) compared with 50% of group A.
3. Discussion Currently, varicocele repair in adolescent patients is recommended in the presence of asymmetrical testicular volume or pain [3]. Despite following these guidelines, infertility has been shown in 20% to 30% [2,10]. The challenge remains to identify patients who are at the highest risk of infertility in early adolescence. Biochemical markers
Table 2
Comparison of semen characteristics (n = 15)
Group No. of Volume Concentration Forward Normal patients (mL) (million/mL) motility morphology (%) (%) A
10
B
5
A vs B
1 (0.5-3) 1.5 (0.5-6) 0.6
26 (8.1-91) 3 (0.7-31) 0.04 ⁎
60 5 (1-8) (43-84) 28 5 (2-7) (18-80) 0.44 0.92
⁎ P b .05; two-tailed Mann-Whitney U test.
Testicular volume and semen parameters in adolescent patients have been correlated with histologic evidence of testicular damage; however, their use and interpretation is controversial [10,11]. This study shows that testicular dysfunction occurs much earlier than previously reported [4,12] in adolescent patients with testicular atrophy. In addition, testicular dysfunction may be detectable before there is a significant change in testicular volume. The authors recognise that small sample size represents a limitation of this study. We plan to increase the sample size and repeat sperm analysis at 18 years of age to determine the effect of treatment on their potential fertility. The findings of the study not only reinforce the importance of sonographic assessment of testicular size but also suggest that sperm parameters may help stratify patients with symmetrical testicular size. Further work is needed to assess if poor sperm concentration and forward motility in early adolescence can predict subfertility in adult life and response to early varicocele surgery.
References [1] Witt MA, Lipshultz LI. Varicocele: a progressive or static lesion? Urology 1993;42:541-3.
385
[2] Zampieri N, Cervellione RM. Varicocele in adolescents: a 6-year longitudinal and follow-up observational study. J Urology 2008;180: 1653-6. [3] Tekgul S, Riedmiller H, Gerharz E, et al. European Association of Paediatric Urology Guidelines on Paediatric Urology. http://www. uroweb.org/gls/pdf/19_Paediatric_Urology.pdf [accessed September 2011]. [4] Diamond DA, Zurakowski D, Bauer SB, et al. Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urology 2007;178:1584-8. [5] Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril 1970;21:606-9. [6] Hirsh AV, Cameron KM, Tyler JP, et al. The Doppler assessment of varicoceles and internal spermatic vein reflux in infertile men. Brit J Urol 1980;52:50-6. [7] Diamond DA, Paltiel HJ, DiCanzio J, et al. Comparative assessment of pediatric testicular volume: orchidometer versus ultrasound. J Urology 2000;164:1111-4. [8] Grubb A. Refusal of treatment (child): competence Re L (medical treatment: Gillick Competency). Medical Law Review 1999;7:58-61. [9] Tocci A, Lucchini C. WHO reference values for human semen. Hum Reprod Update 2010;16:559. [10] Fisch H, Hyun G, Hensle TW. Testicular growth and gonadotrophin response associated with varicocele repair in adolescent males. Brit J Urol Int 2003;91:75-8. [11] Kondo Y, Ishikawa T, Yamaguchi K, et al. Predictors of improved seminal characteristics by varicocele repair. Andrologia 2009;41:20-3. [12] Pinto KJ, Kroovand RL, Jarow JP. Varicocele related testicular atrophy and its predictive effect upon fertility. J Urology 1994;152: 788-90.
www.elsevier.com/locate/jpedsurg
Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele David J.B Keene a,⁎, Yasmin Sajad b , George Rakoczy c , Raimondo M. Cervellione a a
Department of Paediatric Urology, Royal Manchester Children's Hospital, M13 9WL Manchester, United Kingdom Department of Andrology and Fertility, St Mary's Hospital, M13 9WL Manchester, United Kingdom c Department of Paediatric Surgery, Royal Manchester Children's Hospital, M13 9WL Manchester, United Kingdom b
Received 5 November 2011; accepted 10 November 2011
Key words: Semen variables; Adolescent; Varicocele; Testicular volume
Abstract Purpose: Varicocele is potentially a progressive condition that may affect fertility. The authors have encouraged sperm banking for their postpubertal patients with varicocele and aim to evaluate the sperm parameters in this cohort of patients. Methods: With institutional ethical approval, sperm variables (volume, concentration, and forward motility) of patients with postpubertal varicocele who opted for sperm banking were prospectively recorded. The following parameters were also acquired: (a) ultrasound measurement of testicular volume, (b) clinical grade, and (c) venous Doppler. Patients were divided into 2 groups: symmetrical testis (group A) and asymmetrical testis (group B). Testicular asymmetry was defined as greater than 20% difference in testicular volume compared with contralateral testis. Sperm parameters were compared between groups A and B using Mann-Whitney U test and P b .05. Results: Fifteen patients were included: 10 in group A and 5 in group B. Median semen concentration in group B was significantly lower than group A (3 vs 26 million/mL; P = .04). One hundred percent of group B failed World Health Organisation adult criteria for normal spermiograms compared with 50% of group A. Conclusions: Sperm concentration and quality was lower in patients with asymmetrical testis. Testicular dysfunction may be present before the onset of testicular hypotrophy. When testicular hypotrophy is present, testicular dysfunction is very likely. © 2012 Elsevier Inc. All rights reserved.
Idiopathic varicocele is a progressive condition that potentially could cause infertility [1,2]. Current guidelines for adolescents with varicocele focus mainly on the testicular
Presented at the 58th Annual Meeting of the British Association of Paediatric Surgeons, Belfast, Northern Ireland, July 20-22, 2011. ⁎ Corresponding author. Tel.: +44 161 701 2177; fax: +44 161 701 2928. E-mail address: [email protected] (D.J.B. Keene). 0022-3468/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2011.11.035
volume as an indicator of testicular damage [3]. It is known that patients with asymmetry testicular volume have worse semen variables at 18 years [2,4] compared with those with symmetrical testes. Since 2009, the authors have been offering sperm banking to all postpubertal adolescents with varicocele. This study aims to compare semen variables in patients with symmetrical testes with those patients with asymmetrical testes in the presence of idiopathic varicocele.
384
1. Methods
D.J.B. Keene et al. Table 1
Demographic details of patients (n = 15) Group A
Ethical approval was obtained for collecting sperm data from adolescent patients with varicocele (REC 09/H1013/15). These data will form the first part of a randomised study of early surgery vs conservative management. Postpubertal adolescents aged 12 to 17 years with clinically evident left idiopathic varicocele [5] underwent the study. The clinical grade of the varicocele was determined according to the Dubin and Amelar classification [5]. Testicular venous Doppler was performed, and only those with spontaneous venous testicular reflux were included [6]. All patients underwent testicular ultrasound with a 5- to 10-MHz linear probe. Measurements of testicular length, width, and height were obtained using electronic callipers. Testicular volume was then estimated using the formula for a prolate ellipsoid (volume in mL = 0.52 × L × W × H) [7]. Testicular asymmetry was defined as a greater than 20% difference in left testicular volume compared with the contralateral testis [2]. All patients were divided into 2 groups: (a) symmetrical testes and (B) asymmetrical testes. Patients were offered sperm banking at the time of the diagnosis before any intervention. Informed written consent was obtained for semen cryopreservation from all patients. If patients were younger than 16 years, then they had to be Gillick competent [8] before considering sperm banking. Those patients who produced a semen sample by masturbation at the authors' andrology laboratory were included in this study. Semen analysis was performed according to World Health Organisation recommendations (World Health Organisation, 1999) after liquefaction for 20 minutes at 37°C, and the following variables were recorded: semen volume (mL), sperm concentration (million/mL), sperm motility (rapid + forward motility %), and normal morphology (%). Sperm freezing was carried out after dilution into a cryoprotectant medium. Statistical analyses were performed using Stats Direct Package version 2.7.1. Data are expressed as median (range) unless otherwise stated. A 2-sided Mann-Whitney U test was used to compare medians between groups A and B. A P value of less than .05 was accepted as being statistically significant.
2. Results Fifteen patients were included in this study. Ten had symmetrical testicular size (group A), and 5 had asymmetrical testicular size (group B). The median testicular volume differential for group A was 6.9% and that for group B was 30%. Table 1 shows patients' age, varicocele clinical grading, Doppler finding, and testicular volume. The semen volume, forward motility, and morphology were not significantly different between the 2 groups
No. of patients Age of patients (y) a
Group B
10 5 15.6 15.9 (14.7-16.1) (12.5-17.3) 0 0
No. of patients with Grade 1 clinical grade [4] (Valsalva) Grade 2 2 (palpable) Grade 3 8 (visible) No. of patients with Grade 1 0 Doppler grade [5] (Valsalva) 2 Grade 2 (spontaneous intermittent) Grade 3 8 (continuous) Testicular volume 6.9 differential b (%) (0-17.3)
1 4 0 2
3 30 (20-60.8)
a Comparison of ages in group A vs group B is not significant (P = .44). b Testicular volume differential = (volume right testis − volume left testis)/volume of right testis × 100.
(Table 2). However, the median semen concentration in group B was significantly lower compared with that in group A (3 vs 26 million/mL; P = .04). All patients in group B failed World Health Organisation adult criteria for normal spermiograms [9] (either sperm concentration b 20 million/mL or forward motility b 50%) compared with 50% of group A.
3. Discussion Currently, varicocele repair in adolescent patients is recommended in the presence of asymmetrical testicular volume or pain [3]. Despite following these guidelines, infertility has been shown in 20% to 30% [2,10]. The challenge remains to identify patients who are at the highest risk of infertility in early adolescence. Biochemical markers
Table 2
Comparison of semen characteristics (n = 15)
Group No. of Volume Concentration Forward Normal patients (mL) (million/mL) motility morphology (%) (%) A
10
B
5
A vs B
1 (0.5-3) 1.5 (0.5-6) 0.6
26 (8.1-91) 3 (0.7-31) 0.04 ⁎
60 5 (1-8) (43-84) 28 5 (2-7) (18-80) 0.44 0.92
⁎ P b .05; two-tailed Mann-Whitney U test.
Testicular volume and semen parameters in adolescent patients have been correlated with histologic evidence of testicular damage; however, their use and interpretation is controversial [10,11]. This study shows that testicular dysfunction occurs much earlier than previously reported [4,12] in adolescent patients with testicular atrophy. In addition, testicular dysfunction may be detectable before there is a significant change in testicular volume. The authors recognise that small sample size represents a limitation of this study. We plan to increase the sample size and repeat sperm analysis at 18 years of age to determine the effect of treatment on their potential fertility. The findings of the study not only reinforce the importance of sonographic assessment of testicular size but also suggest that sperm parameters may help stratify patients with symmetrical testicular size. Further work is needed to assess if poor sperm concentration and forward motility in early adolescence can predict subfertility in adult life and response to early varicocele surgery.
References [1] Witt MA, Lipshultz LI. Varicocele: a progressive or static lesion? Urology 1993;42:541-3.
385
[2] Zampieri N, Cervellione RM. Varicocele in adolescents: a 6-year longitudinal and follow-up observational study. J Urology 2008;180: 1653-6. [3] Tekgul S, Riedmiller H, Gerharz E, et al. European Association of Paediatric Urology Guidelines on Paediatric Urology. http://www. uroweb.org/gls/pdf/19_Paediatric_Urology.pdf [accessed September 2011]. [4] Diamond DA, Zurakowski D, Bauer SB, et al. Relationship of varicocele grade and testicular hypotrophy to semen parameters in adolescents. J Urology 2007;178:1584-8. [5] Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril 1970;21:606-9. [6] Hirsh AV, Cameron KM, Tyler JP, et al. The Doppler assessment of varicoceles and internal spermatic vein reflux in infertile men. Brit J Urol 1980;52:50-6. [7] Diamond DA, Paltiel HJ, DiCanzio J, et al. Comparative assessment of pediatric testicular volume: orchidometer versus ultrasound. J Urology 2000;164:1111-4. [8] Grubb A. Refusal of treatment (child): competence Re L (medical treatment: Gillick Competency). Medical Law Review 1999;7:58-61. [9] Tocci A, Lucchini C. WHO reference values for human semen. Hum Reprod Update 2010;16:559. [10] Fisch H, Hyun G, Hensle TW. Testicular growth and gonadotrophin response associated with varicocele repair in adolescent males. Brit J Urol Int 2003;91:75-8. [11] Kondo Y, Ishikawa T, Yamaguchi K, et al. Predictors of improved seminal characteristics by varicocele repair. Andrologia 2009;41:20-3. [12] Pinto KJ, Kroovand RL, Jarow JP. Varicocele related testicular atrophy and its predictive effect upon fertility. J Urology 1994;152: 788-90.