re: varicocele: red flag or red herring?

2
accurate in assessing preoperative potency in candidates for bilateral nerve-sparing radical retropubic prostatec- tomy. J Sex Med 2008;5:677–83. [6] Christie KM, Meyerowitz BE, Giedzinska-Simons A, Gross M, Agus DB. Predictors of affect following treatment deci- sion-making for prostate cancer: conversations, cognitive processing, and coping. Psychooncology. 2008 Aug 29 [Epub ahead of print]. Andrea Salonia* Department of Urology, University Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy E-mail address: [email protected] DOI: 10.1016/j.eururo.2008.11.019 Re: Varicocele: Red Flag or Red Herring? Zini A, Boman JM Semin Reprod Med. In press Expert’s summary: Zini and Boman tackle the question of whether to surgically treat men with varicocele presenting with infertility [1]. Consensus based on good data appears to be a pipe dream, as the lack of reliable fertility markers, well-defined study design, and other obstacles such as female factor have resulted in mostly retrospective, noncontrolled studies, with very little hope for future randomized controlled trials. In making the best of limited resources, the authors evaluated available literature to determine the value of varicocelectomy for male infertility. They concluded that although a cause-and-effect relationship cannot be established, compelling evi- dence supports the association between varicocele and impaired fertility as well as the viability of varicocelectomy as a treatment for infertile couples with clinical varicocele. Expert’s comments: The recent meta-analysis by Marmar et al [2] reached a similar conclusion: Varicocelectomy in infertile men with clinical varicocele and at least one abnormal semen parameter improves the odds of spontaneous pregnancy. The authors emphasize the importance of strict study standards. In retro- spect, our quest to answer the broad question of varicocelectomy efficacy using ambiguous outcome measures and without a clear understanding of varicocele pathophysiology seems quixotic at best and foolhardy at worst. As Zini and Boman point out [1], a large randomized controlled study on this topic would be difficult to conduct, especially with the availability of intracytoplasmic sperm injection (ICSI) as a highly effective alternative. The outlook, however, is hopeful. Our under- standing of varicocele has grown slowly but steadily over the years. In the basic sciences, for example, oxidative stress and other mechanisms have been implicated in varicocele pathophysiology [3]. Clin- ical studies have elucidated the effects of varicocele not only on fertility but on steroidogenesis [4,5]. Studies have also demonstrated greater improve- ment in semen parameters with repair of larger and/or bilateral varicoceles [6,7]. Microsurgical technique allows for preservation of the testicular artery and lymphatics, which improves outcomes and reduces complications [8]. Although large-scale trials and meta-analyses have yielded mixed results, many modest studies have contributed small but vital fragments of the puzzle, which may eventually come together to reveal an overall picture of varicocele. As such, future outcomes research should focus on well-defined study groups based on an understanding of varicocele pathophy- siology to reveal which couples, if any, can benefit from varicocelectomy. We should also remember that ICSI, while it can obviate the need for varicocelectomy, is not risk free and requires invasive treatment of the potentially unaffected female partner. Conflicts of interest: The author has nothing to disclose. References [1] Zini A, Boman JM. Varicocele: red flag or red herring? Semin Reprod Med. In press. [2] Marmar JL, Agarwal A, Prabakaran S, et al. Reassessing the value of varicocelectomy as a treatment for male sub- fertility with a new meta-analysis. Fertil Steril 2007;88: 639–48. [3] Shiraishi K, Naito K. Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol 2007; 178:1012–7. [4] Tanrikut C, Choi JM, Lee RK, et al. Varicocele is a risk factor for androgen deficiency. Fertil Steril 2007;88 (Suppl 1):S386. european urology 55 (2009) 522–528 527

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Page 1: Re: Varicocele: Red Flag or Red Herring?

e u r o p e a n u r o l o g y 5 5 ( 2 0 0 9 ) 5 2 2 – 5 2 8 527

accurate in assessing preoperative potency in candidates

for bilateral nerve-sparing radical retropubic prostatec-

tomy. J Sex Med 2008;5:677–83.

[6] Christie KM, Meyerowitz BE, Giedzinska-Simons A, Gross

M, Agus DB. Predictors of affect following treatment deci-

sion-making for prostate cancer: conversations, cognitive

processing, and coping. Psychooncology. 2008 Aug 29 [Epub

ahead of print].

Andrea Salonia*

Department of Urology, University Vita-Salute San Raffaele, Via

Olgettina 60, 20132 Milan, Italy

E-mail address: [email protected]

DOI: 10.1016/j.eururo.2008.11.019

Re: Varicocele: Red Flag or Red Herring?Zini A, Boman JM

Semin Reprod Med. In press

Expert’s summary:Zini and Boman tackle the question of whether tosurgically treat men with varicocele presenting withinfertility [1]. Consensus based on good data appearsto be a pipe dream, as the lack of reliable fertilitymarkers, well-defined study design, and otherobstacles such as female factor have resulted inmostly retrospective, noncontrolled studies, withvery little hope for future randomized controlledtrials. In making the best of limited resources, theauthors evaluated available literature to determinethe value of varicocelectomy for male infertility.They concluded that although a cause-and-effectrelationship cannot be established, compelling evi-dence supports the association between varicoceleand impaired fertility as well as the viability ofvaricocelectomy as a treatment for infertile coupleswith clinical varicocele.

Expert’s comments:The recent meta-analysis by Marmar et al [2]reached a similar conclusion: Varicocelectomy ininfertile men with clinical varicocele and at leastone abnormal semen parameter improves the oddsof spontaneous pregnancy. The authors emphasizethe importance of strict study standards. In retro-spect, our quest to answer the broad question ofvaricocelectomy efficacy using ambiguous outcomemeasures and without a clear understanding ofvaricocele pathophysiology seems quixotic at bestand foolhardy at worst. As Zini and Boman point out[1], a large randomized controlled study on this topicwould be difficult to conduct, especially with theavailability of intracytoplasmic sperm injection(ICSI) as a highly effective alternative.

The outlook, however, is hopeful. Our under-standing of varicocele has grown slowly but steadily

over the years. In the basic sciences, for example,oxidative stress and other mechanisms have beenimplicated in varicocele pathophysiology [3]. Clin-ical studies have elucidated the effects of varicocelenot only on fertility but on steroidogenesis [4,5].Studies have also demonstrated greater improve-ment in semen parameters with repair of largerand/or bilateral varicoceles [6,7]. Microsurgicaltechnique allows for preservation of the testicularartery and lymphatics, which improves outcomesand reduces complications [8]. Although large-scaletrials and meta-analyses have yielded mixedresults, many modest studies have contributedsmall but vital fragments of the puzzle, whichmay eventually come together to reveal an overallpicture of varicocele. As such, future outcomesresearch should focus on well-defined study groupsbased on an understanding of varicocele pathophy-siology to reveal which couples, if any, can benefitfrom varicocelectomy. We should also rememberthat ICSI, while it can obviate the need forvaricocelectomy, is not risk free and requiresinvasive treatment of the potentially unaffectedfemale partner.

Conflicts of interest: The author has nothing to disclose.

References

[1] Zini A, Boman JM. Varicocele: red flag or red herring? Semin

Reprod Med. In press.

[2] Marmar JL, Agarwal A, Prabakaran S, et al. Reassessing

the value of varicocelectomy as a treatment for male sub-

fertility with a new meta-analysis. Fertil Steril 2007;88:

639–48.

[3] Shiraishi K, Naito K. Effects of 4-hydroxy-2-nonenal, a

marker of oxidative stress, on spermatogenesis and

expression of p53 protein in male infertility. J Urol 2007;

178:1012–7.

[4] Tanrikut C, Choi JM, Lee RK, et al. Varicocele is a risk

factor for androgen deficiency. Fertil Steril 2007;88

(Suppl 1):S386.

Page 2: Re: Varicocele: Red Flag or Red Herring?

e u r o p e a n u r o l o g y 5 5 ( 2 0 0 9 ) 5 2 2 – 5 2 8528

[5] Tanrikut C, Choi JM, Rosoff JS, et al. Improvement in serum

testosterone levels after varicocelectomy. Fertil Steril

2007;88(Suppl 1):S386.

[6] Steckel J, Dicker AP, Goldstein M. Relationship between

varicocele size and response to varicocelectomy. J Urol

1993;149:769–71.

[7] Scherr D, Goldstein M. Comparison of bilateral versus

unilateral varicocelectomy in men with palpable bilateral

varicoceles. J Urol 1999;162:85–8.

[8] Goldstein M, Gilbert BR, Dicker AP, et al. Microsurgical

inguinal varicocelectomy with delivery of the testis: an

artery and lymphatic sparing technique. J Urol 1992;148:

1808–11.

Howard H. Kim*

Cornell Institute for Reproductive Medicine, Weill Cornell Medical

College, New York, NY, USA

*Weill Cornell Medical College,

Urology and Reproductive Medicine, Department of Urology,

525 E 68th St, Box 580, New York, NY 10065, United States.

E-mail address: [email protected]

DOI: 10.1016/j.eururo.2008.11.020