Micro-TESE as the latest option for the worst azoospermia scenarios
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Micro-TESE as the latest option for the worst azoospermia scenarios

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  • 1. Sandro Esteves, MD, PhD Director, ANDROFERTCenter for Male Reproduction Campinas, BRAZIL
  • 2. Learning Objectives Learn the definitions and difference between obstructive (OA) and non-obstructive azoospermia (NOA) Overview of conventional sperm retrieval techniques and results for azoospermic men Understand the rationale of using micro-TESE for the worst azoospermia scenarios Micro-TESE: technique and resultsEsteves, 2
  • 3. Azoospermia: Definitions • Complete absence of spermatozoa Azoospermia in the ejaculate after centrifugation • 1-3% male population Prevalence • 10% infertile males • Obstructive Types • NonobstructiveEsteves, Miyaoka & Agarwal.An update on the initial assessment of the infertile male. CLINICS 2011; 66:1-10.
  • 4. Obstructive Azoospermia Features Sperm Retrieval Normal Sperm Production Simple and Effective Mechanical Blockage Main Causes: Sites: ● Epididymis ● Vasectomy, Post-infectious ● Testis ● Congenital (CBAVD) ● Vas deferens ● Iatrogenic, TraumaEsteves, 5
  • 5. Obstructive Azoospermia http://androfert.com.br/videos
  • 6. 100% 100% 97.9% 95.3% CBAVD (N=30) Vasectomy Post-infectious Total (N=142) (N=64) (N=48)Esteves SC, Verza S, Prudencio C, Seol B. Success of percutaneous sperm retrieval and intracytoplasmic sperm injection (ICSI) in obstructive azoospermic (OA) men according to the cause of obstruction. Fertil Steril. 2010;94 (Suppl):S233.
  • 7. Intracytoplasmic Sperm Injection Outcomes UsingEjaculated vs. Surgically-retrieved Sperm from em with Obstructive Azoospermia Ejaculate Epididymis/Testicle 70 73 P >0.05 48 46 51 43 20 12 Fertilization rate %TQE Pregnancy (%) Miscarriage (%) (%)Verza Jr S & Esteves SC. Sperm defect severity rather than sperm source is associated with lower fertilization rates after intracytoplasmic sperm injection. Int Braz J Urol 2008; 34:49-56.
  • 8. Non-obstructive AzoospermiaEsteves, 9
  • 9. Non-obstructive Untreatable Azoospermia condition  Small testes/elevated FSH/”sterile”  Absent or poor production for sperm in ejaculate  Heterogeneity of sperm production: 600-800 seminiferous tubules/testis; Single focus of production adequate to retrieve spermatozoa for ICSI  Goal: To identify and retrieve sperm for ICSI Geographic location unpredictableEsteves, 10
  • 10. Can We Predict Sperm Retrieval Success in NOA? Important because: 1. Can minimize emotional and financial cost of IVF cycles. 2. Can minimize trauma/damage to testis during sperm harvesting.Esteves, 11
  • 11. Predictive Value of Noninvasive Tests for Sperm Retrieval in NOA FSH Testosterone Testicular Volume Verza Jr. & Esteves. Fertil Steril 2011; 96: S53Esteves, 12
  • 12. Predictive Value of Invasive Tests for Sperm Retrieval in NOA Testicular HistopathologyEsteves, 13
  • 13. Predictive Value of Histopathology Results in Sperm Retrieval for men with NOA Sensitivity Specificity Accuracy (95% CI) (95% CI) (%) HYPO 93 (66-100) 70 (54-82) 81.9 MA 64 (31-89) 59 (44-73) SCO 20 (08-37) 20 (07-41) Verza Jr. & Esteves. Fertil Steril 2011; 96: S53Esteves, 14
  • 14. Predictive Value of Testing forSuccessful Sperm Retrieval in NOA
  • 15. Conventional Sperm Retrieval Techniques in NOA Controlled studies Needle Open Biopsy for NOA men Aspiration Friedler et al., 4/37 (11%) 16/37 (43%) Human Reprod 12:1488, 1997 Ezeh et al. 5/35 (14%) 22/35 (63%) Human Reprod 13:3075, 1998Esteves, 16
  • 16. Conventional TESE (open biopsy) in NOA Number of patients 25 20 15 10 5 0 1 2 3 4 7 8 9 10 14 Number of testicular fragments excised Ostad et al., Urology 52:692, 1998.Esteves, 17
  • 17. Testicular Microdissection Micro-TESE• Method to identify site(s) of production – Based on the diameter of seminiferous tubules• Microsurgical approach – Identify site of production – Preserve vasculature of testis – Small quantity of tissue excised Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999;14:131-135.
  • 18. Watch the video at http://androfert.com.br/videos
  • 19. Vascular pattern of testis • Extensive pattern of vessels surrounding the testisPhotomicrograph courtesy JP Jarow, M.D.
  • 20. Intratesticular Anatomy • Parallel arteries and veins surrounding seminiferous tubules • Allows dissection between tubules
  • 21. Microsurgical Identification of Sperm- producing tubules by AppearanceEsteves, 22
  • 22. Micro-TESE vs TESESuccess Rates in Controlled SeriesSchlegel 1999Amer et al. 2000Okada et al. 2002Okubu et al. 2002 53% 41%Tsujimura et al. 2002Ramon et al. 2003 TESE Micro-TESEEsteves et al. 2011 OR = 1.63 (95% CI: 1.32 – 2.01)
  • 23. Microsurgical versus conventional single-biopsy testicular sperm extraction in nonobstructive azoospermia: a prospective controlled study Verza Jr S, Esteves SC. Fertil Steril 2011; 96 (3): S53 TESE Micro-TESEEsteves, 24
  • 24. Microsurgical vs Single-Biopsy TESE in Nonobstructive Azoospermia Controlled series of 60 patients Sperm Retrieval Success Rates Micro-TESE single-biopsy TESE 93% Method Histology categories P=0.0005 64% 64% pairwise comparisons 45% P<0.0001 25% 20% 9% 6% Overall Hypospermatogenesis Maturation Arrest Sertoli-cell Only Microsurgical versus conventional single-biopsy testicular sperm extraction in nonobstructive azoospermia: a prospective controlled studyEsteves, 25 Verza Jr S, Esteves SC. Fertil Steril 2011; 96 (3): S53
  • 25. Microsurgical vs Single-Biopsy TESE in Nonobstructive Azoospermia Sperm retrieval method and Odds Ratio Relative Risk histopathology category [95% Confidence [95% Interval] Confidence Interval] Micro-TESE vs. TESE 3.97 [1.86-8.49] 1.64 [1.18-2.28] HYPO vs. MA 5.15 [1.16-22.97] 1.61 [0.97-2.68] HYPO vs. SCO 29.75 [6.96-127.27] 5.25 [2.53-10.91] MA vs. SCO 5.77 [1.41-23.62] 3.26 [1.38-7.68] Microsurgical versus conventional single-biopsy testicular sperm extraction in nonobstructive azoospermia: a prospective controlled study Verza Jr S, Esteves SC. Fertil Steril 2011; 96 (3): S53Esteves, 26
  • 26. Conventional TESE vs Micro-TESE Tissue RemovalEsteves, 27
  • 27. Microsurgical vs Single-Biopsy TESE in Nonobstructive Azoospermia Tissue Removal Approach Open Large Micro- P- Single-Biopsy TESE value TESE Success Rate 15/60 (25%) 27/60 (45%) 0.02 Tissue Removed (mg) 65 ± 25 8.9 ± 2.5 <0.01 HYPO 58 ± 12 4.2 ± 1.9 MA 68 ± 17 10.1 ± 3.8 SCO 51 ± 9 7.5 ± 3.7 Microsurgical versus conventional single-biopsy testicular sperm extraction in nonobstructive azoospermia: a prospective controlled study Verza Jr S, Esteves SC. Fertil Steril 2011; 96 (3): S53Esteves, 28
  • 28. Chance of Sperm Retrieval by NOA Diagnosis  Cryptorchidism 52-74%  Varicocele 63-68%  Post-infection (mumps, etc.) 67%  Torsion >50%  Post-radiation/chemotherapy 55-75%  Genetic (Klinefelter, Y microdeletion) 0-75%  Idiopathic 50-60% Esteves et al., Fertil Steril 94; 2010; Raman and Schlegel. J Urol.170; 2003; Hopps et al. Hum Reprod. 180, 2003; Damani et al. JCO. 15; 2002Esteves, 29
  • 29. Micro-TESE Results Androfert Experience (2002-2010) No. of Patients 255 % Retrieval Rate 51.1 No. ICSI cycles 328 Mean ± SD Patient Age Male 37.0 ± 7.6 Female 32.4 ± 4.7 Mean ± No. Injected Oocytes 9.8 ± 7.2 Mean ± %2PN Fertilization 43.7 ± 27.9 No. Transfer 298 Mean ± No. Embryos Transferred 2.4 No. Clinical Pregnancy (%) 86 (28.9) No. Live birth (%) 64 (21.5)Esteves, 30
  • 30. Micro-TESE Results Androfert Experience (2002-2010) No. of Babies Born 102 No. Multiple Deliveries (%) 29 (28.4) Mean ± SD Gestational Age 35.5 ± 2.7 Mean ± Birth Weight 2532 ± 601 Gender ratio; boy/girl 1.0/1.3 No. Perinatal Deaths 6 (5.9) No. Birth Defects (%) 3 (2.9)Esteves, 31
  • 31. Micro-TESE: Current Research Subjective (by appearance) identification of sperm- producing tubules Objective (by size) identification of sperm- producing tubulesEsteves, 32
  • 32. Micro-TESE Objective Identification of Sperm-producing TubulesEsteves, 33
  • 33. Normal Maturation ArrestVerza Jr & Esteves, Atlas of Human Reproduction, SBRH 2012
  • 34. Hypospermatogenesis Sertoli cell-onlyVerza Jr & Esteves, Atlas of Human Reproduction, SBRH 2012
  • 35. Tubule Diameter grouped by Presence of Sperm 420 400 380 Max. Tubule Diameter 360 340 320 300 280 260 240 220 200 180 Median 160 25%-75% yes No 5%-95% Raw Data Presence of SpermEsteves, 37 N = 54; Tubule Diameter: KW-H(1;54) = 25,213; p < 0,0001
  • 36. Intraoperative Objective Identification of Sperm-producing Tubules Computer-assisted Sperm RetrievalEsteves, 38
  • 37. Objective Identification of Sperm-producing Tubules 1. Minimize trauma/damage to the testis: minimal tissue excision. 2. Decrease operative time. 3. Facilitate laboratory tissue processing and sperm search. 4. Improve success.Esteves, 39
  • 38. Conclusions Nonobstructive azoospermia: Most severe form of male infertility Not synonymous of sterility Current testing not predictive of successful SR. Heterogenic pattern of sperm production in NOA: Geographic location unpredictable Microsurgical-guided Testicular Sperm Extraction: Significantly higher SRR and chance of fatherhod for men with NOAEsteves, 40