Varicocele

Pathophysiology, Pathophysiology, Diagnosis and Treatment

Varicocele Grade III

W. Aulitzky, MD
Confraternitaet Vienna Weill Cornell Medical College New York

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Varicocele

Varicocele

Incidence in infertile men: 21% 41% VASCULAR PLEXUS FILLED WITH MELANCHOLIC BLOOD Unilateral or bilateral Subclinical (<0.3mm) and clinical (I,II,III) Ambroise Par, 16th century
Benoff S. 2001

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Varicocele Standard Diagnostic Procedure

Varicocele Standard Diagnostic Procedure Valsalva Maneuver

Examination in warm environment Valsalva (supine and horizontal) Testes volumes (bilateral) Scrotal temperature (thermography) Doppler Ultrasound Reflux Scrotal ultrasound Lab tests: Sperm analysis, Hormones

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Varicocele Standard Diagnostic Procedure Orchidometer

Varicocele Standard Diagnostic Procedure Thermography

Quick & easy measurement of testes Facilitates an accurate diagnosis

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Varicocele Standard Diagnostic Procedure Scrotal ultrasound

Pathophysiology of Varicocele 1

Venous Reflux

Dilatation of venous plexus Hydrostatic pressure Testicular temperature Testicular function
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Pathophysiology of Varicocele II New Scientific Data Heat stress Apoptosis Androgen deprivation Toxic elements DNA - Fragmentation Sperm antibodies Excess ROS Genetic defect Age & duration Interstitial edema

Impact of Varicocele on Sperm Quality

sperm concentration progressive sperm motility sperm morphology sperm DNA fragm. class II sperm DNA fragm. class IV inactive mitochondria III
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MULTIFACTORIAL ?
Marmar et al, 2001
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Blumer et al, 2007

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Pathophysiology of Varicocele Hydrostatic Pressure Hydrostatic Pressure

Pathophysiology of Varicocele Increased intracapillary pressure interstitial edema

Normal Testis Interstitial Edema* Efficiency of testosterone transfer and intra- & extracellular communications Impaired testis function
*Harrison et al, 1982
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Testis with Varicocele

H2O Pc ~ 11 mmHg

H2O Pc ~ 25 mmHg

Pathophysiology of Varicocele Apoptosis

Increased germ cell apoptosis in varicocele patients (14.7% vs 2.0%) Simsek et al. 1998 Increased apoptotic cells in ejaculate of varicocele patients (10.0% vs 0.1%) Baccetti et al. 1996 Association of apoptotic cells and CD++ deposition in varicocele patients Hurley et al. 1999

Pathophysiology of Varicocele Sperm DNA

Microsurgical varicocelectomy has a beneficial effect on sperm DNA integrity Sperm denaturation as an index for sperm damage was decreased 6 months after varicocelectomy from 27.7% vs 24.6% (p<0.05)
Zini A et al, 2005

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Results of Varicocele Treatment VENOUS VOLUME & INTERRUPTION OF HYDROSTATIC COLUMN

Varicocele Treatment Criteria No recurrences No complications (hydrocele, hematoma, testicular atrophy) No X-ray exposure (venograms, embolisations) Minimally invasive procedures Preservation of vital structures (test. artery, lymph vessels, muscles, nervs)

TESTICULAR TEMPERATURE
Green et al, 1984 Hurt et al, 1986 Wright et al, 1997
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Varicocele Treatment Different Methods

Varicocele Treatment

High Ligation Varicocelectomy Inguinal Varicocelectomy Spermatic Vein Embolisation Laparoscopic Varicocelectomy Antegrade Sclerosation Microsurgical Varicocelectomy

Laparoscopic Subinguinal Inguinal Antegrade Micro High ligation Sclerosation

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Varicocele Treatment

Varicocele Treatment

High ligation

Inguinal

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Varicocele Treatment

Varicocele Treatment

Laparoscopic Antegrade Sclerosation

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Varicocele Treatment

Varicocele Treatment Goals and Evidence Scrotal temperature and vein volume Pain Pregnancy rate Sperm count Sperm quality Testicular growth in adolescence Hormonal regulation of the testis
Benoff S et al, 2001

Subinguinal Micro

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Varicocele Treatment
Success High ligation Inguinal Embolisation Laparoscopy Sclerosation Micro subinguinal xxx high
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Skin incision of microsurgical subinguinal varicocelectomy

Morb. xxx xx x xx x x Compl. xxx xx xx xx xx x x low
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Remarks invasive

xx xxx xx x xx xxx

X-ray invasive X-ray surg. skills

xx moderate

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Results after microsurg. subing. Varicocelectomy Ligation of testicular artery is unlikely to enhance testicular function.
Testicular artery < 1.5 mm in diameter

N Sperm Count (x 106) Progr. Motility % Pregnancy Rate (Overall) 272 272 272

PRE-OP 57.7 4.2 17.4 0.7

POST-OP 64.3 5.6 28.3 1.3 48%

DIFF S.E.M.

p<0.001 p<0.001

Pregnancy Rate after 12 months 25 % Pregnancy Rate after 24 months 51.5%

Jungwirth A et al, 2001
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Efficacy of Varicocelectomy

Varicocele Treatment Advanced Female Age (>35 years)

Surgical N 110 P<0.05 P<0.05 35% 6% (20%) 41% Result Varicocelectomy is an effective method clinically and economically - for infertile couples with advanced female age.
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Non-Surgical 94 n.s. n.s. 25% 16 (40%) 41%

microsurgical varicocelectomy sperm concentr. sperm motility sperm morphology 9.71 x 10/ml P < 0.00001 9.92% P < 0.0001 3.16% P < 0.01

high ligation 12.03 x 10/ml P < 0.0002 11.7 P < 0.002

Sperm % Sperm Motility Spontaneous Pregnancy ART Pregnancy

Agarwal et al, 2007

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OBrien JH et al, 2004

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Varicocelectomy vs ART Cost Effectiveness

Varicocele Treatment
Induction of Spermatogenesis in azoospermic men after treatment (spermatic vein embolisation)

Delivery rate

Cost/delivery
Before (mill sperm/ml) After (mill sperm/ml) 3.81 1.69 (56.2%) 10.31 1.87 12.11 1.85 p P < 0.03 P < 0.001 P < 0.001

Varicocelectomy ART (IVF/ICSI)

Schlegel PN et al, 1997

30% 28%

$ 26,268 $ 89,091

Azoospermia (0 sperm/ml) Kryptozoospermia (< 0.1 mill sperm/ml) Severe OAT (< 1.0 mill sperm/ml)

0 0.054 0.007 0.54 0.04

Gat Y et al, 2005

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Varicocele Treatment
Benefits of microsurgical varicocelectomy in adolescents
Results of semen analysis Variable Sperm count (x106/ml) Preoperative Postoperative (6 mo) Sperm motility % Preoperative Postoperative (6 mo) Ku JH et al, 2005
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Varicocele Treatment

Adolescents

Fertile Adults

Infertile Adults

P Value

Cochrane Meta Analysis has little Statement Power.

Humke U, 2006

31.7 2.7 40.7 3.4

49.2 10.3 47.1 4.8

18.9 3.0 20.2 4.1

<0.001 0.003

Cochrane Meta Aanalysis should not support Guidelines Recommendation.

Ficcara et al, 2005

41.8 2.6 52.1 2.2

40.5 2.3 43.2 3.0

34.3 2.4 37.3 3.1

0.081 0.003

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Varicocele Treatment

Varicocele and Male Infertility Summary

Varicocele is found in many subfertile men and is considered as a possible cause for male factor infertility

The odds of spontaneous pregnancy after surgical varicocelectomy are between 2.62 2.87
Marmar et al, 2007

In many cases varicocele treatment results in improved male fertility factors and increased pregnancy rates Varicocele treatment seems to be more successful and cost effective than ART Pathophysiology of varicocele is still not fully understood. Recent findings support a co-factor hypothesis We need standardized diagnostic procedures and adequately designed controlled clinical trials including both partners for a better understanding of varicocele induced subfertility

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