References

[1] Yanagimachi R. Germ cell research: a personal perspective. Biol

Reprod 2009;80:204–18.

[2] Seandel M, Rafi S. Reproductive biology: in vitro sperm maturation.

Nature 2011;471:453–5.

Walter Cardona Maya

Grupo Reproduccio

´n, Universidad de Antioquia, Medellı´n, Colombia

E-mail address:

wdcmaya@medicina.udea.edu.co

DOI:

10.1016/j.eururo.2011.05.024

Re: Does Varicocele Repair Improve Male Infertility?

An Evidence-Based Perspective From a Randomized,

Controlled Trial

Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM

Eur Urol 2011;59:455–61

Experts’ summary:

In a prospective, nonmasked, randomized controlled trial, the

authors assessed the e±±icacy o± varicocelectomy with the

primary outcome o± spontaneous pregnancy

[1]

. The authors

examined men with primary or secondary in±ertility who

displayed clinical varicoceles on physical examination and

at least one impaired semen parameter on semen analysis.

Importantly, authors excluded men with subclinical or recur-

rent varicoceles or men with normal sperm parameters.

A total o± 150 men were randomized to either observa-

tion or a microscopic subinguinal varicocelectomy. Only 5

men were lost to ±ollow-up, leaving 145 ±or analysis. A±ter

12 mo o± ±ollow-up, 13.9% o± the observation group and

32.9% o± the treatment group had achieved pregnancy, with

overall improved odds (odds ratio [OR]: 3.04; 95% con±i-

dence interval [CI], 1.33–6.95) o± achieving pregnancy with

varicocelectomy. The authors ±ound a number needed to

treat o± 5.27 (95% CI, 1.55–8.99), which suggests that 5.27

men need to undergo varicocelectomy to achieve one

spontaneous pregnancy.

As a secondary outcome, the authors examined semen

parameters, including sperm concentration, motility, and

morphology, and ±ound signi±icant improvements in all

three parameters a±ter treatment. In contrast, no signi±icant

changes o± semen parameters ±rom baseline were ±ound in

the observation arm.

Experts’ comments:

Despite the ±act that numerous studies have demonstrated the

bene±it o± varicocele repair, many reports have been mired by

methodological limitations. In the era o± evidence-based med-

icine, physicians and patients o±ten demand robust proo± o±

e±±icacy. The most recent Cochrane review on varicocelectomy

showed no improvement in the odds o± pregnancy (OR: 1.10;

95% CI, 0.73–1.68) a±ter varicocele treatment

[2]

. The

Cochrane analysis pooled results o± randomized controlled

trials that assessed e±±icacy o± varicocele treatment, either

surgical varicocelectomy or percutaneous embolization. A

total o± eight studies were included in the meta-analysis,

which examined a total o± 607 men. Un±ortunately, trials that

included men with subclinical varicoceles as well as men with

normal semen analyses were included in the treatment arms

o± the analyzed studies, despite current practice o± discourag-

ing treatment o± such men. When the analysis was restricted

to include only the studies with men who possessed abnormal

semen parameters with clinical varicoceles, only three studies

remained. Although the statistical power was reduced, the OR

suggested a possible bene±it o± varicocele treatment, although

the CI was wide (OR: 2.08; 95% CI, 0.60–4.25).

Manyexpertshave criticized the Cochrane review±or both

its inclusion criteria and its outcome measures. The inclusion

o± trials that enrolled men with subclinical varicoceles and

with normal semen parameters—both groups that are known

not to bene±it ±rom varicocele treatment—weakens any

conclusions that could be reached by a meta-analysis

including such studies. Marmar et al

[3]

per±ormed a

systematic review o± pregnancy outcomes a±ter varicocele

treatment but included only studies o± men with palpable

varicoceles and abnormal semen parameters. Perhaps not

surprisingly, the authors ±ound signi±icantly increased odds

o± pregnancy a±ter varicocele treatment (OR: 2.87; 95% CI,

1.33–6.20).

The current trial is not per±ect. The lack o± adequate

descriptiono±pregnancydetermination,apoordescriptiono±

statistical methods, and a lack o± a time to event analysis ±or

both pregnancy and semen improvement all weakened the

study. Nevertheless, Abdel-Meguid and colleagues are to be

commended ±or continuing to explore a question ±or which

doubt exists in many minds and to improve the level o±

evidence that exists to help in±ertile men with varicoceles.

Conﬂicts of interest:

Dr. Lipschultz is a speaker and consultant ±or

Auxillium and AMS and a consultant ±or Repros. Dr. Eisenberg has nothing

to disclose.

References

[1] Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele

repair improve male in±ertility? An evidence-based perspective ±rom

a randomized, controlled trial. Eur Urol 2011;59:455–61.

[2] Evers JH, Collins J, Clarke J. Surgery or embolisation ±or varicoceles in

sub±ertile men. Cochrane Database Syst Rev 2009, CD000479.

[3] Marmar JL, Agarwal A, Prabakaran S, et al. Reassessing the value o±

varicocelectomy as a treatment ±or male sub±ertility with a new

meta-analysis. Fertil Steril 2007;88:639–48.

Michael L. Eisenberg

, Larry I. Lipshultz

Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

*Corresponding author. Baylor College o± Medicine, Department o±

Urology, 6624 Fannin St., Suite 1700, Houston, TX 77030, USA.

E-mail address:

mleisenb@bcm.edu

(M.L. Eisenberg)

DOI:

10.1016/j.eururo.2011.05.025

EUROPEAN UROLOGY 60 (2011) 392–396

395