Management of Nonobstructive Azoospermia Before Surgical Sperm Retrieval
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This document summarizes the management of non-obstructive azoospermia before attempting sperm retrieval. It discusses evaluating patients for obstructive vs. non-obstructive causes, predicting success of sperm retrieval based on medical history and examination findings, and potential interventions such as varicocele repair and hormone therapy to improve sperm production and increase likelihood of finding sperm.
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Management of Nonobstructive Azoospermia Before Surgical Sperm Retrieval
- 1. Management of NOA before Sperm Retrieval Sandro C. Esteves, MD., PhD. Medical & Scien,fic Director, ANDROFERT Andrology & Human Reproduc,on Clinic Campinas, BRAZIL 4th International Congress - Academy of Clinical Embryologists 18-20 September 2015, Kochi INDIA
- 2. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2015 ANDROFERT
- 3. Azoospermia: the complete lack of sperm in ejaculate aEer centrifugaFon 10-15% infertile males 1-3% male population Cooper et al. Hum Reprod Update 2009; Esteves & Agarwal, Clinics 2013 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2015 ANDROFERT
- 4. Esteves et al Int Braz J Urol 2014; 40: 443-53 Goals of semen analysis are to reduce analytical error and enhance precision Examination of pelleted semen Differentiation between ‘true’ azoospermia and cryptozoospermia Minimum 2 analyses Transient azoospermia due to medical conditions and biological variability Supernatant is discharged Pellet is meticulously examined Centrifugation at 3,000g for 15 minutes ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2015 ANDROFERT
- 5. Prognosis and management differenFally affected by type of azoospermia ObstrucFve Non-‐ obstrucFve Hypo-‐hypo Spermatogenic failure Clinical picture FSH/LH: ñ or nl TT: low or nL Testes: small or nl Normal testes & endocrine profile; Mechanical blockage FSH/LH <1.2 mUI/ mL, Low TT, small tesFs, poor virilizaFon Disrupted Normal Spermatogenesis Esteves et al, Clinics 2011 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2015 ANDROFERT
- 6. Cryptorchidism, testicular trauma, torsion, infection, radio-/ chemotherapy, congenital abnormalities, systemic diseases Small testes (<15 cc; long axis <4.6 cm) Flat epididymis, palpable vas Elevated FSH levels (>7.6 mIU/ml in 90% men) Low testosterone levels (<300 ng/dl in up to 50%) Diagnostic parameters provide >90% prediction of whether azoospermia is due to spermatogenic failure Medical history Physical examination Endocrine profile Esteves et al Clinics 2011 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2015 ANDROFERT
- 7. Verza Jr & Esteves, Atlas of Human Reproduction SBRH 2013 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 NOA associated to maturation arrest is unrevealing Wet examination and cryopreservation if sperm found Hypospermatogenesis Maturation arrest Sertoli cell-only ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2015 ANDROFERT
- 8. Frequency of azoospermia among 2,383 patients attending an Infertility Clinic Esteves et al. Clinics 2011; 66: 691-700. Azoospermia 35% 61% 36% 3% Hypo-hypo OA SF ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2015 ANDROFERT
- 9. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2015 ANDROFERT
- 10. 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 (KS, AZFc) 25-70% Idiopathic 50-60% Etiology cannot determine whether or not sperm will be found within the testis ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2015 ANDROFERT
- 11. FSH levels Testosterone levels Testicular volume elecFng candidates for SR Can biomarkers predict SR success? Diagnostic markers reflect global testicular function but not the presence of a site of active spermatogenesis Verza Jr & Esteves. Fertil Steril 2011; 96 (Suppl.): S53 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 11 2015 ANDROFERT
- 12. Biopsy helpful for counseling but does not provide definitive proof of whether sperm will be found; may jeopardize future retrieval attempts 100% 40.3% 19.5% Hypospermatogenesis Maturation Arrest Sertoli-cell only Presence of sperm within the testicle (N=357) Esteves & Agarwal. Asian J Androl 2014; 16: 642 Testicular histopathology ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2015 ANDROFERT
- 13. Complete AZFa, AZFb or AZFa+b microdeleFons unfavorable prognosis YCMD SR success AZFa nil AZFb nil AZFc 50-‐70% Krausz et al. 2014; Esteves et al. 2013; Esteves 2015 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2015 ANDROFERT
- 14. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 14 2015 ANDROFERT
- 15. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2015 ANDROFERT IntervenFons to inferFle males men with SF prior to a sperm retrieval acempt
- 16. 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 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 16 2015 ANDROFERT
- 17. Among 233 men with SF and clinical varicocele, about 1/3 had motile sperm in postoperative ejaculate Weedin et al J Urol 2010; 183: 2309-15 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 17 2015 ANDROFERT
- 18. MaturaFon arrest and hypospermatogenesis favorable prognosis Weedin et al J Urol 2010;183:2309-‐15 Among 233 men with SF and treated varicocele, 1/3 had moFle sperm in postop. ejaculate ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 18 2015 ANDROFERT
- 19. Inci et al J Urol 2009;182:1500-‐5; Haydardedeoglu et al Urology 2010;75:83-‐6 § Inci 2009 OR: 2.63 (95% CI: 1.05-‐6.60; p=0.03) Although 2/3 remain azoospermic aEer varicocele repair, SRR is increased § Haydardedeoglu 2010 53 30 Treated (N=66) Untreated (N=30) SR success (%) 61 38 Treated (N=31) Untreated (N=65) p<0.01 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 19 2015 ANDROFERT
- 20. MedicaFon Hypogonadism (TT<300 ng/dl) in up to 50% men with SF High ITT levels essen,al for regula,ng spermatogenesis in combina,on with Sertoli cell s,mula,on by FSH Paradoxically weak sFmulaFon of Leydig and Sertoli cells by endogenous gonadotropins Due to high baseline FSH and LH levels the rela,ve amplitudes are low Shiraishi et al Hum Reprod 2012;27:331-‐9; Sussman et al Urol Clin N Am 2008;35:147-‐55 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 20 2015 ANDROFERT
- 21. ITT levels increase aEer hCG; sFmulatory effect on residual spermatogenic areas Shinjo E et al Andrology 2013;1:929-‐35; Shiraishi et al Hum Reprod 2012;27:331-‐9 273 1348 Before After ITT (ng/dl) ITT levels increased aEer hCG-‐based therapy Spermatogonial DNA synthesis increased PCNA expression ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 21 2015 ANDROFERT
- 22. Testosterone and estradiol levels <300 ng/dL (10.4 nmol/L) Hypogonadism category Pure MedicaFon algorithm at Androfert Tx aimed at boosFng T Aromatase 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 T/E raFo <10 Aromatase hyperacFvity T/E raFo >10 (nl) ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 22 2015 ANDROFERT Esteves Asian J Androl 2015;17:1-‐12
- 23. Shiraishi et al Hum Reprod 2012;27:331-‐9; Esteves Int Braz J Urol 2013;39:440 Medical therapy may increase SR success in men with SF MicrodissecFon TESE Rescue ~15% of paFents with previous failed SR acempts ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 23 2015 ANDROFERT
- 24. Esteves Asian J Androl 2015;17:1-‐12 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 24 2015 ANDROFERT
- 25. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 25 2015 ANDROFERT
- 26. OpFons for sperm retrieval in spermatogenic failure Technique Acronym Success TesFcular sperm aspiraFon TESA 15-‐50% TesFcular sperm extracFon TESE 20-‐60% MicrodissecFon tesFcular sperm extracFon Micro-‐ TESE 40-‐67% Esteves et al Int Braz J Urol 2013;37:570-‐83; Deruyver et al Andrology 2014;2:20-‐4 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 26 2015 ANDROFERT
- 27. • Minimal tissue excision • Mechanical mincing • Enzymatic tissue digestion • Avoid iatrogenic damage • Lab air quality control ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 27 2015 ANDROFERT
- 28. 3,412 cycles involving severe male factor inferFlity Individualized COS strategies to retrieve 10-‐15 oocytes per treatment cycle 0% 10% 20% 30% 40% 50% 60% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 20 25 Number of oocytes retrieved Clinical pregnancy Live birth ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 28 2015 ANDROFERT
- 29. Conclusions Best management of NOA prior to SR includes: 1. Proper diagnosis (clinical & endocrine) Ø DeselecFng AZF (a/b) carriers 2. IdenFficaFon of candidates to intervenFons Ø varicocele Rx & medical Tx 3. Carry out SR ≥3 months aEer intervenFons 4. Tailored COS to retrieve 10-‐15 oocytes ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 29 2015 ANDROFERT
- 30. Thank you This presentaFon is available at hcp://www.slideshare.net/ sandroesteves 4th International Congress - Academy of Clinical Embryologists 18-20 September 2015, Kochi INDIA