varicocele in the icis era

Sandro Esteves, MD, PhD

Director, ANDROFERT Center for Male Reproduction and Infertility

Campinas, BRAZIL

Insight’12 – Lite, Coimbatore, India – May 2012

Varicocele: Prevalence Va

ricoc

ee

• 15% male population • 35% of male infertility cases

Esteves, 2

Presenter

Presentation Notes

Approximately 35% of men facing difficulties to conceive have varicocele. Several studies have demonstrated that surgical treatment of clinical varicoceles is highly effective in decreasing seminal oxidative stress, increasing seminal concentrations of antioxidants and improving sperm quality and pregnancy rates. However, current guidelines propose that varicoceles should be treated if palpable and in the presence of abnormal semen analyses.

Varicocele: Physical Examination

Esteves, 3

Varicocele: Use of Pencil-probe Doppler

Esteves, 4

ROS-induced DNA damage

Sertoli Cell

Spermatogonia

Spermatocytes

Early spermatids

Elongated spermatids

Mature spermatozoa

Epididymis

Vas Deferens

Seminiferous Tubules

Alvarez and Sakkas, Fertil Steril, 2010

Varicocele: Pathophysiology

Courtesy of Prof. Juan Alvarez

Sur

gica

l Tr

eatm

ent

• Indication for Treatment: Clinical (palpable) varicocele and Abnormal semen analysis results

Varicocele: Treatment

Esteves, 6

Esteves, 7

Technique Internal Spermatic

Vein Ligation

External Spermatic

Vein Ligation

Recurrence Rate

Hydrocele Formation

Rate

Spontaneous Pregnancy

Rate

Retroperitoneal High-Ligation (Palomo)

Yes No 7-35% 6-10% 25-55%

Laparoscopic Yes No 2-7% 0-9% 14-42% Embolization Yes No 2-24% NR 20-40% Macroscopic Inguinal (Ivanissevich)

Yes Yes 0-37% 7% 34-39%

Microscopic Inguinal or Subinguinal45,51,54,55

Yes Yes 0-0.3% 0-1.6% 33-56%

Surgical Treatment of Varicocele

Miyaoka & Esteves. Critical appraisal on the role of varicocele in male infertility. Adv Urol 2012; Epub Esteves, 8

Fertility Restoration Spontaneous Pregnancy

Surgical Treatment of Varicocele

Esteves, 9

Presenter

Presentation Notes

35% of all men seeking infertility evaluation have varicocele, a condition that disrupts the normal blood flow around the testicles. It has been debated for more than 50 years if the surgical treatment of varicocele is effective or not. Many studies report improvement after surgery, but others show no benefit. We still don’t know why the fertility status of some patients improve after surgery while others don’t; however, recent data show that patient selection may optimize treatment outcomes.

Varicocelectomy for Fertility Restoration

Esteves, 10

Fertil Steril 2007;88:639–48.

Presenter

Presentation Notes

This meta-analysis gives a clear message: only infertile men with palpable varicoceles and with one or more abnormal semen parameters should receive treatment. The key issue here is that patients with normal semen results and/or with nonpalpable varicoceles (including the ones diagnosed only by ultrasound) are NOT candidates for treatment. Surgical removal of palpable varicoceles in men with abnormal semen analysis increased the chances of achieving spontaneous pregnancy by 2.9-fold, as compared to no treatment.

Implications for Practice • Varicocele treatment S

urgi

cal

Trea

tmen

t • Effect • Decrease seminal oxidative stress • Improve sperm DNA integrity • Improve semen parameters • Increase the likelihood of

spontaneous and assisted pregnancy

Esteves, 11

Presenter

Presentation Notes

Several studies have demonstrated that surgical treatment of clinical varicoceles is highly effective in decreasing seminal oxidative stress, increasing seminal concentrations of antioxidants and improving sperm quality and pregnancy rates. However, current guidelines propose that varicoceles should be treated if palpable and in the presence of abnormal semen analyses.

Fertility Improvement

Sperm Retrieval in

Azoospermia

Fertility Improvement

ICSI

Outcomes Fertility Restoration Spontaneous Pregnancy

Surgical Treatment of Varicocele • It can improve success of ART

Esteves, 12

Presenter

Presentation Notes

The main goal of varicocele treatment has been the restoration of fertility and unassisted conception. However, this objective is unlikely to be achieved in the cases of severe male factor infertility; in these circumstances, ART will be needed to overcome infertility. I am quite sure that you think that varicocele treatment is such cases is a waste of time. I will challenge your beliefs by showing 2 clinical situations in where varicocele treatment may be indicated prior to assisted reproduction. In these situations, the goal would be fertility improvement rather than fertility restoration.

Varicocele Repair Before ICSI

Microsurgical varicocele repair prior

to ICSI (N=80)

ICSI in the presence of varicocele (N=162)

6.7

15.4

Total Number of Motile Sperm (x106)

Pre-op Post-op

P<0.01

Clinical Outcome of Intracytoplasmic Sperm Injection in Infertile Men With Treated and Untreated Clinical Varicocele

SC Esteves, FV Oliveira, RP Bertolla. ANDROFERT, Center for Male Reproduction, Campinas, BRAZIL and Division of Urology, São Paulo Federal

University, São Paulo, BRAZIL.

The Journal of Urology Vol. 184,1442-1446, October 2010

Esteves, 13

Presenter

Presentation Notes

In this study, patients with palpable varicoceles and severely abnormal semen analyses received 2 types of treatment: in one group varicoceles were microsurgically-repaired before ICSI and in the other ICSI was performed in the presence of untreated varicoceles. Semen analyses results improved after surgery, but still remained below the threshold levels for normality.

78%*

46%*

22%

66%

31% 31%

Varicocele and ICSI Outcomes

Treated Varicocele Untreated Varicocele

Fertilized Eggs (%2PN)

Live Birth (%)

*P<0.05

Miscarriage (%)

Esteves SC, Oliveira FV, Bertolla RP. Clinical Outcome of ICSI in Infertile Men with Treated and Untreated Clinical Varicocele. J Urol 2010;184:1442-1446

Odds ratio 1.87 0.43 95% CI 1.08 - 3.25 0.22 – 0.84 P-value 0.03 0.01

Esteves, 14

Presenter

Presentation Notes

Although fertility was not restored, semen quality improvement positively impacted on the fertilization rates and pregnancy outcomes by ICSI compared to the group of patients in whom the varicocele remained untreated. Logistic regression analyses showed that chance of achieving a live birth was increased by 1.9-fold while the chances of miscarriage was decreased by 2.3X when the varicocele was treated before ICSI.

Varicocele Repair Before Sperm Retrieval Sperm Retrieval and Intracytoplasmic Sperm Injection in Men With Nonobstructive Azoospermia, and Treated and

Untreated Varicocele K Inci, M Hascicek, O Kara et al. Department of Urology, School of

Medicine, Hacettepe University, Ankara, Turkey.

The Journal of Urology Vol. 182,1500-1505, October 2009

53% 30%

Successful Sperm Retrieval Rate

Treated VaricoceleUntreated Varicocele

OR: 2.63 (95% CI: 1.05-6.60; P=0.03)

Microsurgical varicocele repair prior to sperm retrieval ICSI

(N=66)

Sperm Retrieval in the presence of varicocele

(N=30)

Esteves, 15

Presenter

Presentation Notes

Another clinical situation is the patient with azoospermia and Palpable varicoceles. In this study, the treatment of palpable varicoceles prior to sperm retrieval significantly increased the chance of finding sperm within the testicles. The authors showed that SR rates were increased 2.6 times in the varicocele had been repaired before sperm retrieval.

Take-home Messages Evidence for a Positive Impact in the Surgical Treatment of Clinical

Varicoceles : 1. Increase the likelihood of spontaneous

conception in men with mild/moderate abnormal semen parameters.

2. Increase the odds of live birth in subgroups of men with severe oligozoospermia

undergoing ICSI. 3. Increase the chance of having a successful

sperm retrieval in the subgroup of patients with non-obstructive azoospermia.

Esteves, 16

varicocele in the icis era

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