Surgical Treatment of Male Infertility

1
Surgical Treatment of Male Infertility

• Selahittin Çayan, M.D.
• Associate Professor of Urology
• Department of Urology
• University of Mersin School of Medicine

2
Upgrading Fertility Status
Natural conception
IUI
IVF/ICSI
Decreasing Risk and Cost
Increased Desirability
Ejaculated sperm
Surgical sperm retrieval for IVF/ICSI
Donor sperm insemination Adoption
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Why Evaluate the Infertile Male in Era of ART?

• Pathophysiology-specific treatment
• Diagnose correctable pathologies
• Varicocele ? Progressive damage
• Total loss of fertility possible
• ? Testosterone ?Erectile dysfunction, decreased
  lipido
• Diagnose life threatened disease
• 37 times higher incidence of testis cancer
• Prolactinoma
• Detect genetic disease
• 30-100 times higher incidence of genetic
  abnormalities

4
Positive effect of pathophysiologic specific
treatment of male infertility on ART

• To obviate the need for ART
• To downstage the level of ART needed to bypass
  male factor infertility
• From IUI to spontaneous pregnancy
• F rom IVF/ICSI to IUI
• To increase pregnancy rates with ART in cases who
  had improved sperm morphology after the treatment

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Evaluation of Infertile Man
History Physical examination Semen analysis (2x)
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Varicocele
Hormonal evaluation Radiologic evaluation
TREATMENT
20
Advanced fertility tests Genetic
tests Biopsy/Cytology
Obstruction Non-obstruction
30
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Total Motile Sperm Count

• Ejaculate volume x sperm density x motile
  fraction (ab)
• Volume 3 ml.
• Density 10 million/ml.
• Motility 30

9 million
7

Reasonable Alternatives

Total Motile Sperm Count Sex gt20
million IUI 5-20 million IVF 1.5 -5
million ICSI lt1.5 million TMC Ejaculate
volume x sperm concentration x motile fraction
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Etiology of Male Factor Infertility

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Correctable Pathologies of Male Infertility

• Varicocele
• Obstructive azoospermia
• Ejaculatory duct obstruction
• Hormonal abnormality
• Infection
• Ejaculatory dysfuntion
• Gonadotoxin exposure

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Varicocele
Semen abnormalities Density Motility
Morphology Testicular volume ? Leydig cell
function ?
WHO, Fertil Steril, 1992
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Approach in infertile men with varicocele

• Treatment of Varicocele
• Surgery (Open, laparoscopic)
• Microsurgical Varicocelectomy
• Radiologic embolization
• Assisted Reproductive Technologies
• IUI, IVF/ICSI

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Guidelines on Treatment of Varicocele

• Varicocelectomy should not be offered to improve
  fertility, since pregnancy rates do not increase.
• National Collaborating Centre for Womens and
  Childrens Health 2005
• Treatment of varicocele should be offered to
  infertile men with palpable varicocele and
  abnormal semen analysis.
• Best Policies Practice Groups of the AUA 2002
• Best Policies Practice Groups of the ASRM
  2004
• Treatment of varicocele is still controversial,
  although it improves spontaneous pregnancy rates.
• EAU Guideline on Male infertility
  2004

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Treatment of Varicocele Systematic review-2003

• Selected 7 studies or abstracts (1979-2002)
• Inclusion-exclusion criterias ?
• Treatment Control
• Pregnancy rates 21.7 19.3
• Odds ratio 1.01 (95 CI 0.73-1.4)
• Recommendation Treatment of varicocele does not
  improve fertility in unexplained infertility.

Evers and Collin, Lancet, 2003
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Varicocelectomy- Meta analiysis-2004

• Selected 8 randomized controlled study
  (1985-2004)
• Inclusion criterias
• Subclinic varicocele (3 papers)
• Clinical varicocele normal semen analiysis (2
  papers)
• Varicocele ? Abnormal semen parameters (3
  papers)
• Comparison Pregnancy rates
• Peto Odds ratio 1.1 (95 CI 0.73-1.68)
• Recommendation Treatment of varicocele does not
  improve fertility in unexplained infertility.

Evers and Collin, Cochrane Database Syst Rev 2004
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Turkish Society of Andrology Guidelines on
Varicocele
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Varicocele Diagnosis and Evaluation
Physical examination Grade 1 Palpable with
Valsalva Grade 2 Direct palpable Grade 3
Visible with no palpation
Türk Androloji Dernegi, Varikosel Kilavuzu, 2005
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Endications for treatment of Varicocele

• Infertility
• Symptomatic varicocele

Türk Androloji Dernegi Varikosel Kilavuzu, 2005
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Varicocelectomy-Meta analysis-2006

• Selected 8 randomized clinical studies
• Exclusion criterias from the meta-analysis
• Subclinical varicocele
• Normal semen analysis
• Inclusion criterias to the meta-analysis
• Clinical palpable varicocele
• Abnormal semen parameters
• 3 randomized studies matching to the criterias
• Tedavi grubu (n 120)
• Kontrol grubu (n 117)

Ficarra V et al, Eur Urol 2006
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Varicocelectomy-Meta analysis-2006

• Treatment Control P value
• Pregnancy rates 36.4 20
  0.009

Ficarra V et al, Eur Urol 2006
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• Inclusion criterias
• Infertility
• Abnormal semen analysis
• Palpable varicocele
• Surgical techniques
• High ligation
• Inguinal
• Microsurgical
• 24 months of postop follow-up
• Spontaneous pregnancy rates

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Varicocelectomy- Meta-analysis-2007

• 5 randomized clinical studies
• Treatment group (n 396)
• Control group (n 174)
• Treatment Control
• Pregnancy rates 33 15.5

Marmar J et al, Fertil Steril 2007
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Best Candidates for Varicocelectomy

• Palpable, large varicocele
• Normal testicular volume
• Normal FSH/testosterone, inhibin B?
• Total Motile Spermgt 5 million
• No genetic abnormality
• Short infertility duration

Fretz PC Sandlow JI, Urol Clin North Am,
2002 Türk Androloji Dernegi, Varikosel Kilavuzu,
2005
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Improvement after Varicocelectomy

• Sperm concentration 66
• Sperm motility 70
• Pryor and Howards, 1987
• 50 increase in TMC 34 - 54
• Spontaneous pregnancy 31 - 43
• Çayan et al, Urology, 2000
• Çayan et al, Urology, 2001
• Çayan et al, J Urol, 2002

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Varikosel tedavisinde en iyi teknik hangisi?

• Dahil edilme kriterleri
• Infertilite
• Anormal semen analizi
• Palpabl varikosel
• Tüm tedavi gruplari
• Açik cerrahi
• Laparoskopik
• Radyolojik
• Karsilastirma
• Spontan gebelik oranlari
• Komplikasyonlar

• 36 klinik çalisma
• Yüksek ligasyon, Palomo (n10)
• Mikrocerrahi (n12)
• Laparoskopik (n5)
• Radyolojik (n6)
• Makroskopik (n3)

Çayan Kadioglu, Submitted Review, Eur Urol, 2008
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Varikosel tedavisinde en iyi teknik hangisi?

• Ortalama gebelik 39.07 (1748/4473)
• Yüksek ligasyon 37.69
• Mikrocerrahi 41.97
• Laparoskopik 30.07
• Radyolojik 33.2
• Makroskopik 36
• P degeri 0.001

P0.001
Çayan Kadioglu, Submitted Review, Eur Urol, 2008
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Varikosel tedavisinde en iyi teknik hangisi?

• Nüks () Hidrosel
  ()
• Yüksek ligasyon 14.97 8.24
• Mikrocerrahi 1.05 0.44
• Laparoskopik 4.3 2.84
• Radyolojik 12.7
• Makroskopik 2.63 7.3
• P degeri 0.001 0.001
• Radyolojik basarisiz girisim 13.05
• Laparoskopik major komplikasyon 7.59

P0.001
Çayan Kadioglu, Submitted Review, Eur Urol, 2008
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Microsurgical Varicocelectomy
n540 Postop follow-up 36.4 22.8 months
(14 - 64) Pozitive response 50.2 Negative
response 49.8 50 increase in
TMS Spontaneous pregnancy 36.6 Time to
achieve pregnancy 7 3.4 months (1 - 19 months)
Çayan S et al, J Urol, 2002
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Preoperative TMS- Post op. Spontaneous pregnancy

Kadioglu A Çayan S, ASRM 2001
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ART vs. Varicocelectomy?Changes in ART Candidacy
POSTOPERATIVE
Çayan S Kadioglu A, J Urol 2002
PREOPERATIVE
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Cost

• Per delivery
• ICSI 89,091 USD
• Varicocelectomy 26,268 USD

Schlegel , Urology, 1997
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Effect of Varicocelectomy on ART Success

• First IVF-ET-unsuccess then varicocelectomy,
  Pregnancy
• 31 (Yamamoto 1994)
• 40 (Ashkenazi 1989)
• Varicocelectomy versus IUI ?
• Pregnancy Delivery
• Op - (n34) 6.3 1.6
• Op (n24) 11.8 11.8

Daitch et al, J Urol, 2001
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Poor prognosis for IUI

• Female age (gt37)
• Previous pelvic surgery
• Decreased semen parameters
• Total motile sperm countlt5 million
• Sperm motility (lt40)
• Untreated varicocele

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Sperm morphology (Kruger)
Preop Postop Kibar Y et
al. 2.6 10.2 J Urol, 2002 Çayan S et
al. 3.3 4.7 J Urol, 2002 In 13, seminal
response (-) ? Pregnancy () Kruger 3.7
? 6.2 Improvement in Kruger morphology may
predict pregnancy.
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Varicocele repair

• The best treatment modality is microsurgical
  repair with the lowest complication rate and the
  highest spontaneous pregnancy rates.
• Varicocelectomy has significant potential not
  only to obviate the need for ART, but also to
  downstage the level of ART needed to bypass male
  factor infertility.
• A cost effective treatment of infertility
• Upgrade to normal semen Allow natural pregnancy
  (40)
• Upgrade from azoospermia to oligospermia (20-30)
• Allow fresh sperm for IUI or IVF/ICSI
• Even if patients remain azoospermic, it may
  preserve foci of spermatogenesis for Testicular
  sperm recovery (TESA/TESE)

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Infertility - Azoospermia 5-20

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Correctable Pathologies in Azoospermic Men

• Non-obstructive azoospermia
• Varicocele
• Endocrine-Hormonal abnormalities
• Gonadotoxins
• Smoking, tobacco, alcohol, mariuhana, cocaine
• Radiation
• Drugs Cimetidine, nitrofurantoin, GABA agonists,
  nifedipin, sulfonamide, ketoconazol,
  diethilstilbestrol, Chemotherapeutics,
  corticosteroids
• Insecticide (DDT), pesticide
• Termal (heating, hut tub, saunas), Pb, solvent
• Treatment Treatment of underlying pathology
• Semen analysis after 3-12 months
• Obstructive azoospermia
• Epididymal obstruction
• Vas deferens obstruction
• Distal ejaculatory duct obstruction
• Treatment Surgery

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Surgical treatment alternatives

• Obstructive azoospermia
• Vasovasostomy
• Epididymovasostomy
• MESA
• Macroscopic TESA
• TUR-ED
• Non-obstructive azoospermia
• Microscopic TESE
• Microscopic varicocelectomy

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Vasovasostomy- Epididymovasostomy

• Patency 60-99.5
• Spontaneous pregnancy 40-60

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Transurethral resection of Ejaculatory Duct
(TUR-ED)

• Endoscopic resection of veru-montanum

Results of TUR-ED Postop. follow-up 26 ?8.5
months (12-63)
Total (n 38) Improvement in seminal parameters (74) Spontaneous pregnancy (13)
Complet obs. 59 9
Partial obs. 94 19
Kadioglu et al, Fertil Steril, 2001
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Upgrading from Nothing to Something

• Obstructive azoospermia
• Microsurgical reconstruction
• Success rate 60-100
• Pregnancy 30-60
• No need for additional surgical procedure for
  sperm retrieval
• Candidates for IUI or ICSI with fresh motile
  sperm from ejaculate
• Upgrade from azoospermia to normal semen
  parameters
• Upgrade from azoospermia to oligospermia for IUI
  or ICSI

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Ejaculatory Dysfunction-Anejaculation
Reasons for anejaculation Spinal cord
injury Pelvic and retroperitoneal surgery
Psychogenic causes Idiopathic Multi
ple sclerosis Diabetes Prolactinoma
Overall 61.1 (11/18) of couples achieved
pregnancy
Çayan Turek, Fertil Steril, 2001
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Summary

• Achieving natural pregnancy, while ideal, should
  not be the only measurement of treatment
  efficacy.
• Clinicians should offer treatment that improves
  the long term fertility status of the couples,
  not just to achieve immediate pregnancy.
• Pathophysiologic specific treatment in male
  infertility has significant potential not only to
  obviate the need for ART, but also to downstage
  the level of ART needed to bypass male factor
  infertility.
• Effective treatment may be surgical, medical or
  simple lifestyle modifications.
• Upgrade from nothing to IVF/ICSI
• Upgrade from IVF/ICSI to IUI
• Upgrade from IUI to natural pregnancy