Clinical management of men with nonobstructive azoospermia - Steps Before Sperm Retrieval
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Reproductive Andrology Workshop III 17-21 January 2016 - Kuwait City - KUWAIT Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health Lecture 3: Steps Before Sperm Retrieval in Nonobstructive Azoospermia
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Clinical management of men with nonobstructive azoospermia - Steps Before Sperm Retrieval
- 1. REPRODUCTIVE ANDROLOGY SURGERY WORKSHOP III 17-21 January 2016 – Reproductive Medicine Unit – Jahra Hospital KUWAIT CLINICAL MANAGEMENT OF MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Lesson 3: Steps Before Sperm Retrieval Dr Sandro ESTEVES Medical and Scientific Director ANDROFERT - Andrology & Human Reproduction Clinic Campinas, Brazil
- 2. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2016 ANDROFERT
- 3. Interven'ons to infer'le males men with SF prior to a sperm retrieval a5empt ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2016 ANDROFERT
- 4. Medica'on 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 s'mula'on 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, 4 2016 ANDROFERT
- 5. Study Study design Study group Medication Findings Pavlovich et al. 2001 Case series 43 men with T/E ratio <10 Testolactone No effect Hussein et al. 2005 Prospective cohort 42 men with favorable hystology 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) ! Aromatase inhibitors and gonadotropins have been used with variable results Esteves Asian J Androl 2015;17:1-‐12 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2016 ANDROFERT
- 6. ITT levels increase aVer hCG; s'mulatory 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 aVer hCG-‐based therapy Spermatogonial DNA synthesis increased PCNA expression ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2016 ANDROFERT
- 7. Testosterone and estradiol levels <300 ng/dL (10.4 nmol/L) Hypogonadism category Pure Medica'on algorithm at Androfert Tx aimed at boos'ng 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 ra'o <10 Aromatase hyperac'vity T/E ra'o >10 (nl) Esteves Asian J Androl 2015;17:1-‐12 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2016 ANDROFERT
- 8. 1Shiraishi 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 Microdissec'on TESE Rescue ~15% of pa'ents with previous failed SR a5empts1 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2016 ANDROFERT
- 9. Esteves Asian J Androl 2015;17:1-‐12 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2016 ANDROFERT
- 10. 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 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2016 ANDROFERT
- 11. 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, 11 2016 ANDROFERT
- 12. 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, 12 2016 ANDROFERT
- 13. Matura'on 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 mo'le sperm in postop. ejaculate ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2016 ANDROFERT
- 14. 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 after varicocele repair, sperm retrieval success increased in treated individuals § 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, 14 2016 ANDROFERT
- 15. Key Messages – Day 3 Steps before Sperm Retrieval ANDROFERT § 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 ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2016 ANDROFERT
- 16. Thank you This presenta'on is available at h5p://www.slideshare.net/ sandroesteves اشكر