1. Surgical Treatment of Male Infertility
Selahittin Çayan, M.D.
Associate Professor of Urology
Department of Urology
University of Mersin School of Medicine

2. Surgical sperm retrieval Donor sperm insemination
Upgrading Fertility Status
Natural conception
IUI
IVF/ICSI
Increased
Desirability
Decreasing
Risk and Cost
Ejaculated sperm
Surgical sperm retrieval
for IVF/ICSI
Donor sperm insemination
Adoption

3. 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
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

5. Radiologic evaluation Advanced fertility tests
Evaluation of Infertile Man
History
Physical examination
Semen analysis (2x) 10
Varicocele
Hormonal evaluation
Radiologic evaluation
TREATMENT 20
Advanced fertility tests
Genetic tests
Biopsy/Cytology
Obstruction
Non-obstruction 30

6. Total Motile Sperm Count
Ejaculate volume x sperm density x motile fraction (a+b)
Volume: 3 ml.
Density: 10 million/ml.
Motility: 30%
9 million

7. Reasonable Alternatives
Total Motile Sperm Count*
Sex > million
IUI million
IVF million
ICSI < million
* TMC: Ejaculate volume x sperm concentration x motile fraction

8. Etiology of Male Factor Infertility%

9. Correctable Pathologies of Male Infertility
Varicocele
Obstructive azoospermia
Ejaculatory duct obstruction
Hormonal abnormality
Infection
Ejaculatory dysfuntion
Gonadotoxin exposure

10. Varicocele Semen abnormalities Density Motility Morphology
Testicular volume ↓
Leydig cell function ↓
WHO, Fertil Steril, 1992

11. Approach in infertile men with varicocele
Treatment of Varicocele
Surgery (Open, laparoscopic)
Microsurgical Varicocelectomy
Radiologic embolization
Assisted Reproductive Technologies
IUI, IVF/ICSI

12. Guidelines on Treatment of Varicocele
Varicocelectomy should not be offered to improve fertility, since pregnancy rates do not increase.
National Collaborating Centre for Women’s and Children’s 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

13. Treatment of Varicocele: Systematic review-2003
Selected 7 studies or abstracts ( )
Inclusion-exclusion criterias: ?
Treatment Control
Pregnancy rates 21.7% 19.3%
Odds ratio: 1.01 (95% CI: )
Recommendation: Treatment of varicocele does not improve fertility in unexplained infertility.
Evers and Collin, Lancet, 2003

14. Varicocelectomy- Meta analiysis-2004
Selected 8 randomized controlled study ( )
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: )
Recommendation: Treatment of varicocele does not improve fertility in unexplained infertility.
Evers and Collin, Cochrane Database Syst Rev 2004

15. Turkish Society of Andrology: Guidelines on Varicocele

16. Varicocele: Diagnosis and Evaluation
Physical examination:
Grade 1: Palpable with Valsalva
Grade 2: Direct palpable
Grade 3: Visible with no palpation
Türk Androloji Derneği, Varikosel Kılavuzu, 2005

17. Endications for treatment of Varicocele
Infertility
Symptomatic varicocele
Türk Androloji Derneği Varikosel Kılavuzu, 2005

18. 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

19. Varicocelectomy-Meta analysis-2006
Treatment Control P value
Pregnancy rates % %
Ficarra V et al, Eur Urol 2006

20. Inclusion criterias:
Infertility
Abnormal semen analysis
Palpable varicocele
Surgical techniques:
High ligation
Inguinal
Microsurgical
24 months of postop follow-up
Spontaneous pregnancy rates

21. Varicocelectomy- Meta-analysis-2007
5 randomized clinical studies
Treatment group (n: 396)
Control group (n: 174)
Treatment Control
Pregnancy rates 33% %
Marmar J et al, Fertil Steril 2007

22. Best Candidates for Varicocelectomy
Palpable, large varicocele
Normal testicular volume
Normal FSH/testosterone, inhibin B↓
Total Motile Sperm> 5 million
No genetic abnormality
Short infertility duration
Fretz PC & Sandlow JI, Urol Clin North Am, 2002
Türk Androloji Derneği, Varikosel Kılavuzu, 2005

23. Improvement after Varicocelectomy
Sperm concentration 66%
Sperm motility 70%
Pryor and Howards, 1987
50% increase in TMC %
Spontaneous pregnancy %
Çayan et al, Urology, 2000
Çayan et al, Urology, 2001
Çayan et al, J Urol, 2002

24. Varikosel tedavisinde en iyi teknik hangisi?
Dahil edilme kriterleri:
İnfertilite
Anormal semen analizi
Palpabl varikosel
Tüm tedavi grupları
Açık cerrahi
Laparoskopik
Radyolojik
Karşılaştırma:
Spontan gebelik oranları
Komplikasyonlar
36 klinik çalışma:
Yüksek ligasyon, Palomo (n:10)
Mikrocerrahi (n:12)
Laparoskopik (n:5)
Radyolojik (n:6)
Makroskopik (n:3)
Çayan & Kadıoğlu, Submitted Review, Eur Urol, 2008

25. Varikosel tedavisinde en iyi teknik hangisi?
Ortalama gebelik: % (1748/4473)
Yüksek ligasyon: % 37.69
Mikrocerrahi: % 41.97
Laparoskopik: % 30.07
Radyolojik: % 33.2
Makroskopik: % 36
P değeri: 0.001
P=0.001
Çayan & Kadıoğlu, Submitted Review, Eur Urol, 2008

26. Varikosel tedavisinde en iyi teknik hangisi?
Nüks (%) Hidrosel (%)
Yüksek ligasyon:
Mikrocerrahi:
Laparoskopik:
Radyolojik:
Makroskopik:
P değeri:
Radyolojik başarısız girişim: % 13.05
Laparoskopik major komplikasyon: % 7.59
P=0.001
Çayan & Kadıoğlu, Submitted Review, Eur Urol, 2008

27. Microsurgical Varicocelectomy
n=540
Postop follow-up: 36.4 ± 22.8 months
( )
Pozitive response: 50.2%
Negative response: 49.8%
* 50% increase in TMS
Spontaneous pregnancy: 36.6%
Time to achieve pregnancy: 7 ± 3.4 months ( months)
Çayan S et al, J Urol, 2002

28. Preoperative TMS- Post op. Spontaneous pregnancy%
Kadıoğlu A & Çayan S, ASRM 2001

29. ART vs. Varicocelectomy? Changes in ART Candidacy
POSTOPERATIVE
Çayan S & Kadıoğlu A, J Urol 2002
PREOPERATIVE

30. Cost Per delivery ICSI: 89,091 USD Varicocelectomy: 26,268 USD
Schlegel , Urology, 1997

31. 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 - (n:34): 6.3% 1.6%
Op + (n:24): 11.8% 11.8%
Daitch et al, J Urol, 2001

32. Poor prognosis for IUI Female age (>37) Previous pelvic surgery
Decreased semen parameters
Total motile sperm count<5 million
Sperm motility (<40%)
Untreated varicocele

33. Sperm morphology (Kruger)
Preop Postop
Kibar Y et al. 2.6% %
J Urol, 2002
Çayan S et al. 3.3% 4.7%
In 13%, seminal response (-)  Pregnancy (+) Kruger: 3.7%  6.2%
Improvement in Kruger morphology may predict pregnancy.

34. 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)

35. Infertility - Azoospermia: 5-20%

36. 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

37. Surgical treatment alternatives
Obstructive azoospermia:
Vasovasostomy
Epididymovasostomy
MESA
Macroscopic TESA
TUR-ED
Non-obstructive azoospermia:
Microscopic TESE
Microscopic varicocelectomy

38. Vasovasostomy- Epididymovasostomy
Patency: %
Spontaneous pregnancy: 40-60%

39. 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%
Kadıoğlu et al, Fertil Steril, 2001

40. Upgrading from “Nothing” to “Something
Obstructive azoospermia
Microsurgical reconstruction
Success rate: %
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

41. Ejaculatory Dysfunction-Anejaculation
Reasons for anejaculation:
· Spinal cord injury
· Pelvic and retroperitoneal surgery
· Psychogenic causes
· Idiopathic
· Multiple sclerosis
· Diabetes
· Prolactinoma
Overall 61.1% (11/18) of couples achieved pregnancy
Çayan & Turek, Fertil Steril, 2001

42. 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