Testicular Failure in Humans: Current Management and Future Perspectives
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This document summarizes a presentation on testicular failure in humans. It discusses the current management and future perspectives on this condition. Some key points include: - Spermatogenic failure is a challenging condition affecting 1% of men and is usually irreversible. About 40-50% of men with this condition still have residual spermatogenesis that can be retrieved. - Diagnostic tests are not always accurate in predicting if sperm can be found, but a genetic assessment of the Y chromosome can provide helpful information. - Different management approaches are used at Androfert clinic, including counseling, identifying candidates that may benefit from interventions before sperm retrieval, selecting the best sperm retrieval method, and using advanced lab techniques.
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Testicular Failure in Humans: Current Management and Future Perspectives
- 1. V ISABR 2014 Testicular Failure in Humans Current Management and Future Perspectives Sandro C. Esteves, MD., PhD. Medical Director, ANDROFERT Campinas, Brazil
- 2. Learning objectives At the completion of this talk participants should be able to: • Overview the technical aspects of ICSI as carried out in humans • Understand why spermatogenic failure (SF) is one of the most challenging condition in human reproduction • Learn how we manage men with SF seeking fertility at Androfert ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2014 OCTOBER
- 3. Testicular Failure in Humans Current Management and Future Perspectives http://www.androfert.com.br/review ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2014 OCTOBER
- 4. ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2014 OCTOBER
- 5. Spermatogenic failure is the worst prognostic condition in male infertility § Up to 1% of all men; 10-15% of infertile males § Irreversible condition; often termed as “sterile” § Semen analysis reveals “Azoospermia” Should be confirmed in multiple specimens after examination of pelleted semen Esteves & Agarwal. Sperm Retrieval Techniques; In: Gardner et al. Human Assisted Reproductive Technology. Cambridge, pp. 41-53, 2011 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2014 OCTOBER
- 6. Spermatogenic failure is an irreversible condition Congenital Testicular dysgenesis/cryptorchidism Genetic abnormalities (Klinefelter syndrome, Yq microdeletions, etc.) Acquired Testicular torsion; Trauma Post-inflammatory (eg. Mumps orchitis) Exogenous factors (eg. Cytotoxic drugs, irradiation) Testicular cancer Systemic diseases (eg. Liver cirrhosis, renal failure) Idiopathic (Unknown etiology) Esteves et al. Clinics 2011; 66: 691-700 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2014 OCTOBER
- 7. Goals of semen analysis are to reduce analytical error and enhance precision Examination of pelleted semen Differentiation between ‘true’ azoospermia (lack of any sperm) and cryptozoospermia (very few sperm) Minimum 2-3 analyses Transient azoospermia due to medical conditions and biological variability Centrifugation at 3,000g for 15 minutes Esteves et al Int Braz J Urol 2014; 40: 443-53 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2014 OCTOBER Supernatant is discharged Pellet is meticulously examined
- 8. Prognosis and management differentially affected by type of azoospermia Azoospermia Obstructive Non-obstructive Types Spermatogenic failure Hypo-hypo Clinical Picture NL testes NL FSH, LH, TT Mechanical blockage FSH/LH: ñ or nl TT: low or nL Testes: small or nl FSH/LH <1.2 mUI/mL, Low TT, small testis, poor virilization Spermatogenesis Normal ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2014 OCTOBER Disrupted
- 9. Diagnostic parameters provide >90% prediction of whether azoospermia is due to spermatogenic failure Medical history Cryptorchidism, testicular trauma, torsion, infection, radio-/ chemotherapy, congenital abnormalities, systemic diseases Physical examination Small testes (<15 cc; long axis <4.6 cm) Flat epididymis, palpable vas Endocrine profile Elevated FSH levels (>7.6 mIU/ml in 90% men) Low testosterone levels (<300 ng/dl in up to 50%) ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2014 OCTOBER Esteves et al Clinics 2011
- 10. Isolated diagnostic biopsy rarely indicated provide no definitive proof of whether sperm will be found; may jeopardize future retrieval attempts Differential diagnosis with obstructive azoospermia Work-up in SF associated to maturation arrest is unrevealing Wet examination and cryopreservation if sperm found Hypospermatogenesis Maturation arrest Sertoli cell-only Verza Jr & Esteves, Atlas of Human Reproduction SBRH 2013 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2014 OCTOBER
- 11. Obstructive azoospermia is a favorable prognostic condition in male infertility Management options include reconstructive surgery and ART Sperm retrieval highly successful regardless of cause of obstruction and method of retrieval ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 11 2014 OCTOBER OBSTRUCTIVE AZOOSPERMIA OA (N=146) 100% 96.6% 96.3% CBAVD Vasectomy Post-‐infection Esteves et al. J Urol. 2013;189: 232-7
- 12. ICSI outcome in obstructive azoospermia comparable with fertile donors Obstructive azoospermia (N=146) Donor sperm (N=40) 64 61 47 34 61 66 50 38 2PN Fertilization (%) High quality embryos (%) Clinical pregnancy (%) Live birth (%) ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2014 OCTOBER p=NS Esteves et al. Asian J Androl 2014; 16: 602-6
- 13. Hypogonadotropic hypogonadism favorable prognosis and simple management Series of men with adult-onset hypo-hypo Recombinant hCG (Ovitrelle 250 mcg); SC, qw Baseline Posttreatment Esteves & Papanikolaou Fertil Steril 2011; 96 (Suppl.): S230 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2014 OCTOBER
- 14. Frequency of azoospermia among 2,383 patients attending an Infertility Clinic 3% 36% Esteves et al. Clinics 2011; 66: 691-700. ANDROFERT androfert.com.br Azoospermia 35% ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 14 2014 OCTOBER 61% Hypo-hypo OA SF
- 15. About 40-50% of men with SF have residual spermatogenesis within the testis § Not enough for sperm to appear in ejaculate § 600-800 seminiferous tubules § Goal is identify site of production and retrieve sperm for ICSI § Geographic location unpredictable Esteves et al. Sperm Retrieval Techniques. Int Braz J Urol 2011; 37: 570-83 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2014 OCTOBER
- 16. Challenges faced by health professionals providing care for men with SF are manifold § Counseling about the chances of finding testicular sperm § Usefulness of any medical intervention before sperm retrieval § Which sperm retrieval method to apply § Reproductive potential of retrieved gametes in ICSI treatment § Health of offspring ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 16 2014 OCTOBER
- 17. Clinical management of men with spermatogenic failure at Androfert 1. Counsel about the chances of finding sperm for ICSI 2. Select who could benefit from interventions before sperm retrieval 3. Select the best SR method 4. Use of state-of- art lab techniques to handle the retrieved gametes ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 17 2014 OCTOBER
- 18. Clinical management of men with spermatogenic failure at Androfert ANDROFERT androfert.com.br 1. Counsel about the chances of finding sperm for ICSI 2. Select who could benefit interventions before sperm retrieval ANDROFERT from ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 18 2014 OCTOBER 3. Select the best SR method 4. Use of state-of- art lab techniques to handle the retrieved gametes
- 19. elec%ng candidates for SR Can biomarkers predict SR success? Diagnostic markers reflect global testicular function but not the presence of a site of active spermatogenesis FSH levels Testosterone levels Testicular volume ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 19 2014 OCTOBER Verza Jr & Esteves. Fertil Steril 2011; 96 (Suppl.): S53
- 20. Biopsy helpful for counseling but does not provide definitive proof of whether sperm will be found; may jeopardize future retrieval attempts Presence of sperm within the 100% testicle (N=357) 40.3% 19.5% Hypospermatogenesis Maturation Arrest Seroli-cell only Esteves & Agarwal. Asian J Androl 2014; 16: 642 Testicular histopathology ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 20 2014 OCTOBER
- 21. Etiology cannot determine whether or not sperm will be found within the testis Esteves et al Fertil Steril 2010; Raman & Schlegel J Urol 2003; Hopps et al. Hum Reprod 2003; Damani et al JCO 2002 Etiology category Success in finding sperm Cryptorchidism 52-74% Post-infection 67% Torsion >50% Post-chemotherapy/RT 25-75% Genetic 25-70% Idiopathic 50-60% ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 21 2014 OCTOBER
- 22. Genetic assessment of AZF region within the Y chromosome helpful to determine the chances of finding testicular sperm Microdeletions within AZF region found in up to 15% of men with SF Hamada et al. Clinics 2013; 68 (Suppl 1): 39-60; Krausz et al. Andrologia 2014; 2: 5-19 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 22 2014 OCTOBER
- 23. Multiplex-PCR molecular diagnosis of YCMD #4 Normal male #5 AZFb microdeletion #6 AZFc microdeletion Krausz et al. Andrologia 2014; 2: 5-19 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 23 2014 OCTOBER
- 24. Complete AZFa, AZFb or AZFa+b microdeletions unfavorable prognosis; SR not recommended ✕ ✕ ✕ nil nil 50-70% Hamada et al. 2013; Krausz et al. 2014; Esteves et al. 2013 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 24 2014 OCTOBER Chances of finding sperm within the testis
- 25. 1. Counseling about chances of finding sperm and who are candidates for SR Key messages § Diagnostic parameters not accurate to determine if residual spermatogenesis exists § YCMD screening mandatory to “deselect” men with AZFa-b deletions from undergoing SR § Male offspring of fathers with AZFc microdeletions will inherit the Yq deletion (infertility) ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 25 2014 OCTOBER
- 26. Clinical management of men with spermatogenic failure at Androfert 2. Identify who may benefit from interventions before sperm retrieval ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 26 2014 OCTOBER
- 27. Rationale for medication Paradoxically weak stimulation of Leydig and Sertoli cells by endogenous gonadotropins - Due to high baseline FSH and LH levels the relative amplitudes are low Hypogonadism (TT<300 ng/dl) in up to 50% men with SF - High ITT levels essential for regulating spermatogenesis in combination with Sertoli cell stimulation with FSH Shiraishi et al Hum Reprod 2012; 27: 331-9; Sussman et al Urol Clin N Am 2008; 35: 147-55 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 27 2014 OCTOBER
- 28. ANDROFERT androfert.com.br Study Study design Study group Medication Findings Pavlovich Case series 43 men with et al. 2001 T/E ratio <10 Testolactone No effect Hussein et Prospective al. 2005 cohort 42 men with favorable hystology ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 28 2014 OCTOBER Clomiphene Sperm found in SA in 64.3%; All men who remained azoospermic had success at SR Selman et al. 2006 Prospective cohort 49 men with maturation arrest rec-hFSH and hCG No return of sperm in ejaculate; posttreatment SRR were 21.4% Ramasamy et al. 2009 Case series 56 men with nonmosaic Klinefelter Testolactone or anastrozole, alone or combined with hCG SRR increased by 1.4-fold Reifsnyder et al. 2012 Retrospective cohort 307 men with hypogonadis m Aromatase inhibitors, hCG or Clomiphene, alone or combined No effect Shiraishi et al. 2012 Prospective cohort 28 men with idiopathic SF hCG alone or combined with rec-hFSH SR success in 21% of the treated men vs. none in untreated men Hussein et al. 2013 Prospective cohort 612 unselected men Clomiphene alone or combined with hCG or hMG Sperm found in SA in 10.9% of treated males; SRR higher in men who remained azoospermic and treated (57.0 vs. 33.6%, p<0.001) ! There may be a role for medical treatment but more studies are needed
- 29. Mechanism of action unclear but may be related to high ITT that stimulate residual spermatogenic areas ITT (ng/dl) 273 1348 Before After ITT levels increased after hCG-based therapy Spermatogonial DNA synthesis increased Shinjo E et al Andrology 2013; 1: 929-35; Shiraishi et al Hum Reprod 2012; 27: 331-9. ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 29 2014 OCTOBER PCNA expression
- 30. Medication algorithm at Androfert Testosterone and estradiol levels <300 ng/dL (10.4 nmol/L) Hypogonadism category Pure Treatment aimed at boosting endogenous T production Aromatas e inhibitor (anastrozole 1mg orally qid) Rec-hCG (250 mcg SC qw); rec-FSH added (75 IU SC biw) if FSH levels <1.5 mIU/ml ANDROFERT androfert.com.br T/E ratio <10 T/E ratio >10 (nl) ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 30 2014 OCTOBER Aromatase hyperactivity
- 31. Varicocele associated with impaired spermatogenesis Proposed mechanisms include heat-mediated stress and ischemia Spermatogonia B, pachytene spermatocytes and early spermatids highly vulnerable to heat stress Agarwal, Hamada & Esteves Nature Rev Urol 2012; 9: 678-90 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 31 2014 OCTOBER
- 32. Rationale for varicocele repair Catch-up testicular growth among adolescents following varicocele repair Improvement in sperm parameters after varicocele repair Abnormally-low T restored to normal levels in some men after varicocele repair Wang et al Fertil Steril 1991; 55: 152-5; Su et al J Urol 1995; 154: 1752-5; Çayan et al J Urol 2002; 168: 929731-4; Hamada et al Nat Rev Urol 2013; 10: 26-37 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 32 2014 OCTOBER
- 33. Among 233 men with SF and clinical varicocele, about 1/3 had motile sperm in ANDROFERT androfert.com.br postoperative ejaculate ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 33 2014 OCTOBER Weedin et al J Urol 2010; 183: 2309-15
- 34. Varicocele success depend on the presence of spermatogenesis in histopathology Maturation arrest and hypospermatogenesis favorable prognosis ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 34 2014 OCTOBER Weedin et al J Urol 2010; 183: 2309-15
- 35. Although 2/3 remain azoospermic after varicocele repair, sperm retrieval success increased in treated individuals § Inci 2009 OR: 2.63; 95% CI: 1.05-6.60; p=0.03) § Haydardedeoglu 2010 Inci et al J Urol 2009; 182: 1500-5; Haydardedeoglu et al Urology 2010; 75:83-6 SR success (%) p<0.01 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 35 2014 OCTOBER 53 30 Treated (N=66) Untreated (N=30) 61 38 Treated (N=31) Untreated (N=65)
- 36. 2. Identify who may benefit from interventions before sperm retrieval Key messages ANDROFERT androfert.com.br § Medication to boost endogenous T production seems beneficial to improve spermatogenesis, particularly in men with low T levels and low T/E ratio § Repair of clinical varicocele should be considered in ICSI candidates before SR ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 36 2014 OCTOBER
- 37. Clinical management of men with spermatogenic failure at Androfert 1. Counsel about the chances of finding sperm for ICSI 2. Select who could benefit from interventions before sperm retrieval 3. Select the best sperm retrieval method 4. Use of state-of- art lab techniques to handle the retrieved gametes ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 37 2014 OCTOBER
- 38. Methods for sperm retrieval in SF include percutaneous and open surgical procedures Technique Acronym Success Testicular Sperm Aspiration TESA 15-50% Testicular Sperm Extraction TESE 20-60% Microdissection Testicular Sperm Extraction Micro- TESE 40-67% Esteves et al Int Braz J Urol 2013; 37: 570-83; Deruyver et al Andrology 2014; 2: 20-4 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 38 2014 OCTOBER
- 39. Microsurgical method yields higher success regardless of histopathology findings 45% Sperm Retrieval Success Rates Micro-TESE single-biopsy TESE 93% 64% 64% 25% 20% 9% 6% Overall Hypospermatogenesis Maturation Arrest Sertoli-cell Only Controlled series (N=60) Histology categories pairwise comparisons: p<0.0001 Method P=0.0005 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 39 2014 OCTOBER Verza Jr & Esteves. Fertil Steril 2011; 96 (Suppl.): S53
- 40. Esteves SC Int Braz J Urol 2013; 39(3):440 http://androfert.com.br/videos
- 41. 3. Selecting the best sperm retrieval method Key message Microsurgical testicular sperm extraction is key in SF ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 41 2014 OCTOBER
- 42. Clinical management of men with spermatogenic failure at Androfert 1. Counsel about the chances of finding sperm for ICSI 2. Select who could benefit from interventions before sperm retrieval 3. Select the best SR method 4. Use of state-of- art lab techniques to handle the retrieved gametes ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 42 2014 OCTOBER
- 43. • Optimize sperm retrieval • Mechanical mincing • Enzymatic tissue digestion • Avoid iatrogenic damage ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 43 2014 OCTOBER
- 44. Tissue removed (mg) Large Single- Biopsy TESE Micro- TESE P-value 65 ± 25 8.9 ± 2.5 <0.01 Optimizing sperm retrieval Conven6onal TESE Micro-‐TESE Fragment weight Fragment weight Verza Jr & Esteves Fertil Steril 2011; Esteves & Varghese J Reprod Sci 2013 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 44 2014 OCTOBER
- 45. Morphometric Evaluation of Seminiferous Tubules ANDROFERT androfert.com.br 420 400 380 360 340 320 300 280 260 240 220 200 180 ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 45 2014 OCTOBER Median 25%-75% 5%-95% Raw Data yes No Presence of Sperm 160 Max. Tubule Diameter Verza Jr S, Esteves SC. Fertil Steril 2012; 98: S242 N=54; Tubule Diameter: KW-H (1;54) = 25.2; P<0.001
- 46. ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 46 2014 OCTOBER
- 47. Clean Room Technology & ICSI Results 2,315 patients; 14,660 embryos On average, one top-quality additional embryo for transfer or cryopreservation ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 47 2014 OCTOBER Esteves & Bento. Reprod Biomed Online 2013; 26: 9-21
- 48. 4. Using state-of-art lab techniques to handle gametes of men with SF Key messages § Increase the chances of finding sperm from extracted testicular tissue § Avoid iatrogenic damage to the already compromised gametes § Optimize ICSI outcome ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 48 2014 OCTOBER
- 49. What we have achieved after doing this herculeous effort ANDROFERT androfert.com.br 41.4 Spermatogenic failure (N=365) ANDROFERT 47.0 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 49 2014 OCTOBER 43.3 20.0 Sperm retrieval success (%) 2PN fertilization after ICSI (%) High quality embryo generated by ICSI (%) Live birth per treatment cycle (%) Esteves et al Asian J Androl 2014; 16: 602-6
- 50. Why we do all that ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 50 2014 OCTOBER
- 51. What about the health of resulting ANDROFERT androfert.com.br ANDROFERT offspring ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 51 2014 OCTOBER Esteves et al Asian J Androl 2014; 16: 602-6
- 52. NeoHneaatltahl oOf uotffcsopmrineg o rfe Baassbuierisn gBorn but a call for continuous monitoring needed due to limited data and lack of long-term follow-up Region N Outcome analyzed Main findings Palermo et al. 1999 USA 22 Congenital abnormalities No difference with obstructive azoospermia 4.5% vs 1.3% Vernaeve et al. 2005 Belgium 61 Perinatal data; Congenital abnormalities Lower gestational age (singletons); Increased frequency of premature twins; No difference with OA (4% vs 3%) Fedder et al 2007 Denmark 76 Congenital abnormalities No difference with other infertility categories (0% vs 4.0%) Belva et al.; 2011 Belgium 193 Perinatal data; Congenital abnormalities Similar perinatal outcomes; no difference 4.2% SF vs 5.2% OA (ns) Esteves & Agarwal. Clinics 2013; 68 (Suppl.1): 141-50 ANDROFERT androfert.com.br ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 52 2014 OCTOBER
- 53. What the future holds for men with ANDROFERT androfert.com.br spermatogenic failure… ANDROFERT ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 53 2014 OCTOBER