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

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Presentation on theme: "Surgical Treatment of Male Infertility Selahittin Çayan, M.D. Associate Professor of Urology Department of Urology University of Mersin School of Medicine."— Presentation transcript:

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

2 Natural conception IUI Decreasing Risk and Cost Upgrading Fertility Status IVF/ICSI Ejaculated sperm Increased Desirability 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  From IVF/ICSI to IUI  To increase pregnancy rates with ART in cases who had improved sperm morphology after the treatment

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

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 Total Motile Sperm Count* Sex>20 million IUI5-20 million IVF million ICSI<1.5 million * TMC: Ejaculate volume x sperm concentration x motile fraction Reasonable Alternatives

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 EAU Guideline on Male infertility 2004

13  Selected 7 studies or abstracts ( )  Inclusion-exclusion criterias: ? TreatmentControl  Pregnancy rates21.7%19.3%  Odds ratio: 1.01 (95% CI: )  Recommendation: Treatment of varicocele does not improve fertility in unexplained infertility. Evers and Collin, Lancet, 2003 Treatment of Varicocele: Systematic review-2003

14  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 Varicocelectomy- Meta analiysis-2004

15 Turkish Society of Andrology: Guidelines on Varicocele

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

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 Treatment Control P value Pregnancy rates 36.4% 20% Ficarra V et al, Eur Urol 2006 Varicocelectomy-Meta analysis-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  5 randomized clinical studies  Treatment group (n: 396)  Control group (n: 174) TreatmentControl  Pregnancy rates33% 15.5% Marmar J et al, Fertil Steril 2007 Varicocelectomy- Meta-analysis-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 concentration66%  Sperm motility70%  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 Çayan & Kadıoğlu, Submitted Review, Eur Urol, 2008 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)

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

26 P=0.001 Varikosel tedavisinde en iyi teknik hangisi? Nüks (%)Hidrosel (%) Nüks (%)Hidrosel (%)  Yüksek ligasyon:  Mikrocerrahi:  Laparoskopik:  Radyolojik:12.7  Makroskopik:  P değeri: Radyolojik başarısız girişim: % Laparoskopik major komplikasyon: % 7.59 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 Çayan S et al, J Urol, 2002

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

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

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) 40% (Ashkenazi 1989) Varicocelectomy versus IUI ? PregnancyDelivery 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 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. Sperm morphology (Kruger)

34  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) Varicocele repair

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 Vasovasostomy Epididymovasostomy Epididymovasostomy MESA MESA Macroscopic TESA Macroscopic TESA TUR-ED TUR-ED _ Non-obstructive azoospermia: Microscopic TESE Microscopic TESE Microscopic varicocelectomy Microscopic varicocelectomy

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

39 Transurethral resection of Ejaculatory Duct (TUR-ED) Endoscopic resection of veru-montanum 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 Results of TUR-ED Postop. follow-up: 26  8.5 months (12-63)

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 Çayan & Turek, Fertil Steril, 2001 Overall 61.1% (11/18) of couples achieved pregnancy

42  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 Summary


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