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Surgical Treatment of Male Infertility

Surgical Treatment of Male Infertility. Selahittin Ç ayan, M.D. Associate Professor of Urology Department of Urology University of Mersin School of Medicine. Upgrading Fertility Status. Natural conception. IUI. IVF/ICSI. Increased Desirability. Decreasing Risk and Cost.

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Surgical Treatment of Male Infertility

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  1. SurgicalTreatment of MaleInfertility 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 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-specifictreatment • Diagnosecorrectablepathologies • Varicocele→ Progressivedamage • Total loss of fertilitypossible • ↓ Testosterone→Erectiledysfunction, decreasedlipido • Diagnose life threateneddisease • 37 timeshigherincidence of testis cancer • Prolactinoma • Detectgeneticdisease • 30-100 timeshigherincidence of geneticabnormalities

  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. 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 >20 million IUI 5-20 million IVF 1.5 -5 million ICSI <1.5 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 • Ejaculatoryductobstruction • Hormonalabnormality • Infection • Ejaculatory dysfuntion • Gonadotoxinexposure

  10. Varicocele Semen abnormalities Density MotilityMorphology Testicularvolume ↓ Leydigcellfunction ↓ 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 • Varicocelectomyshould not be offeredtoimprovefertility, since pregnancyrates do not increase. NationalCollaboratingCentreforWomen’sandChildren’sHealth 2005 • Treatment of varicoceleshould be offeredtoinfertile men withpalpablevaricoceleandabnormal semen analysis. BestPoliciesPracticeGroups of the AUA 2002 BestPoliciesPracticeGroups of the ASRM 2004 • Treatment of varicocele is stillcontroversial, although it improvesspontaneouspregnancyrates. EAU Guideline on Maleinfertility 2004

  13. Treatment of Varicocele: Systematicreview-2003 • Selected 7 studiesorabstracts (1979-2002) • Inclusion-exclusioncriterias: ? TreatmentControl • Pregnancyrates 21.7% 19.3% • Oddsratio: 1.01 (95% CI: 0.73-1.4) • Recommendation: Treatment of varicoceledoes not improvefertility in unexplainedinfertility. Evers and Collin, Lancet, 2003

  14. Varicocelectomy- Meta analiysis-2004 • Selected 8 randomizedcontrolledstudy (1985-2004) • Inclusioncriterias: • Subclinicvaricocele (3 papers) • Clinicalvaricocele + normal semen analiysis (2 papers) • Varicocele ? + Abnormal semen parameters (3 papers) • Comparison: Pregnancyrates • PetoOddsratio: 1.1 (95% CI: 0.73-1.68) • Recommendation: Treatment of varicoceledoes not improvefertility in unexplainedinfertility. EversandCollin, CochraneDatabaseSystRev 2004

  15. TurkishSociety of Andrology: Guidelines on Varicocele

  16. Varicocele: DiagnosisandEvaluation Physicalexamination: Grade 1: PalpablewithValsalva Grade 2: Directpalpable Grade 3: Visiblewith no palpation Türk Androloji Derneği, Varikosel Kılavuzu, 2005

  17. Endicationsfortreatment of Varicocele • Infertility • Symptomaticvaricocele Türk Androloji Derneği Varikosel Kılavuzu, 2005

  18. Varicocelectomy-Meta analysis-2006 • Selected 8 randomizedclinicalstudies • Exclusioncriteriasfromthe meta-analysis: • Subclinicalvaricocele • Normal semen analysis • Inclusioncriteriastothe meta-analysis: • Clinicalpalpablevaricocele • Abnormal semen parameters • 3 randomizedstudiesmatchingtothecriterias • Tedavi grubu (n: 120) • Kontrol grubu (n: 117) Ficarra V et al, Eur Urol 2006

  19. Varicocelectomy-Meta analysis-2006 TreatmentControl P value Pregnancyrates 36.4% 20% 0.009 Ficarra V et al, EurUrol 2006

  20. Inclusioncriterias: • Infertility • Abnormal semen analysis • Palpablevaricocele • Surgicaltechniques: • Highligation • Inguinal • Microsurgical • 24 months of postopfollow-up • Spontaneouspregnancyrates

  21. Varicocelectomy- Meta-analysis-2007 • 5 randomizedclinicalstudies • Treatmentgroup (n: 396) • Controlgroup (n: 174) TreatmentControl • Pregnancyrates 33% 15.5% Marmar J et al, Fertil Steril 2007

  22. BestCandidatesforVaricocelectomy • 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, UrolClin North Am, 2002 Türk Androloji Derneği, Varikosel Kılavuzu, 2005

  23. Improvement after Varicocelectomy • Sperm concentration66% • Sperm motility70% • Pryor and Howards, 1987 • 50% increase in TMC 34 - 54% • Spontaneous pregnancy31 - 43% • 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, SubmittedReview, EurUrol, 2008

  25. 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 değeri: 0.001 P=0.001 Çayan & Kadıoğlu, SubmittedReview, EurUrol, 2008

  26. 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 değeri: 0.001 0.001 Radyolojik başarısız girişim: % 13.05 Laparoskopikmajor komplikasyon: % 7.59 P=0.001 Çayan & Kadıoğlu, SubmittedReview, EurUrol, 2008

  27. MicrosurgicalVaricocelectomy n=540 Postopfollow-up:36.4 ± 22.8 months (14 - 64) Pozitiveresponse: 50.2% Negative response: 49.8% * 50% increase in TMS Spontaneouspregnancy: 36.6% Time toachievepregnancy: 7 ± 3.4 months(1 - 19 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) PreopPostop Kibar Y et al. 2.6% 10.2% J Urol, 2002 Çayan S et al. 3.3% 4.7% J Urol, 2002 In 13%, seminalresponse (-)  Pregnancy (+) Kruger: 3.7%  6.2% Improvement in Krugermorphologymaypredictpregnancy.

  34. Varicocelerepair • Thebesttreatmentmodality is microsurgicalrepairwiththelowestcomplication rate andthehighestspontaneouspregnancyrates. • 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 costeffectivetreatment of infertility: • Upgradeto normal semen: Allownaturalpregnancy (40%) • Upgradefromazoospermiatooligospermia (20-30%) • Allowfresh sperm for IUI or IVF/ICSI • Evenifpatientsremainazoospermic, it maypreservefoci of spermatogenesisforTesticular 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: 60-99.5% • Spontaneous pregnancy: 40-60%

  39. Transurethral resection of Ejaculatory Duct (TUR-ED) Endoscopicresection of veru-montanum Results of TUR-ED Postop. follow-up: 26 8.5 months (12-63) Kadıoğlu et al, Fertil Steril, 2001

  40. 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

  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 • Achievingnaturalpregnancy, while ideal, should not be theonlymeasurement of treatmentefficacy. • Cliniciansshouldoffertreatmentthatimprovesthelongtermfertilitystatus of thecouples, not justtoachieveimmediatepregnancy. • Pathophysiologicspecifictreatment in maleinfertilityhas significant potential not only to obviate the need for ART, but also to downstage the level of ART needed to bypass male factor infertility. • Effectivetreatmentmay be surgical, medicalorsimplelifestylemodifications. • Upgradefromnothingto IVF/ICSI • Upgradefrom IVF/ICSI to IUI • Upgradefrom IUI tonaturalpregnancy

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