Induction of Spermatogenesis in Azoospermic Men after Varicocele Repair - PowerPoint PPT Presentation

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Induction of Spermatogenesis in Azoospermic Men after Varicocele Repair

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  1. Induction of Spermatogenesis in Azoospermic Men after Varicocele Repair Hasan Farsi K.A. University Hospital King Faisal Specialist Hospital Jeddah

  2. Case Report • 26y male with 1ry infertility of 3y. • Examination: Bilateral normal testes, Bilateral grade II varicocele. • Semen x2 Azooepermia, Volume 2-3cc, normal semen fructose • FSH was normal. • Bilateral inguinal varicocelectomy, testicular biopsy: • Hypospermatogenisis

  3. 18 months later one child • Semen: • Volume: 1.5 cc • Conc.: 3 m/cc • Motility: 25%

  4. Varicocele • 10-15% general population • 40% 1ry infertility • 80% 2ry infertility

  5. Ambroïse Paré (1500–1590): a clinical problem • Barfield, late 19th century: Relationship to infertility • Lipshultz, 1979: Relationship to testicular atrophy that is progressive with age • Kass and Belman, 1987:significant increase in testicular volume after varicocele repair in adolescents

  6. Clinical study of varicocele: the results of long-term follow-up. • Sixty-four infertile male patients with varicocele : • Varicocelectomy 31 cases • No surgery 30 cases • The mean follow-up duration was 76.2 months • The pregnancy rate: (60%) VS (28%) Int J Urol. 2002 Aug;9(8):455-61.

  7. Surgery Vs Observation • 146 men left varicocelectomy • 62 men refused surgery treated with tamoxiphene • Followed up for at least 1 year • Improvement in semen parameters: • 83.2% VS 32.3% • Pregnancy within 1 year: • 62(46.6%) VS 8 (12.9%) (p<0.001). Eur Urol. 2001 Mar;39(3):322-5.

  8. Is varicocelectomy really beneficial in the treatment of male factor infertility?

  9. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. • A meta-analysis was performed to evaluate both randomized controlled trials and observational studies using a new scoring system. • Adjust and quantify for various potential sources of bias, including selection bias, follow-up bias, confounding bias, information or detection bias, and other types of bias, such as misclassification • Of 136 studies identified through the electronic and hand search of references, only 17 studies met our inclusion criteria

  10. …..continue • Statistically significant improvement in: • Concentration • Motility • Morphology • CONCLUSIONS: Surgical varicocelectomy significantly improves semen parameters in infertile men with palpable varicocele and abnormal semen parameters. Agarwal A, Department of Obstetrics Gynecology, Cleveland Clinic Urology. 2007 Sep;70(3):532-8

  11. Varicocelectomy Improves Intrauterine Insemination Success Rates in Men with Varicocele. • 24 pts 63 intrauterine insemination cycles without varicocele treatment. • 34 pts 101 intrauterine insemination cycles following varicocelectomy. • No statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups. • The pregnancy rate per cycle = 6.3 VS 11.8, p = 0.04 • Live birth rate per cycle =1.6 VS 11.8, p = 0.007 • Conclusion: A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting Daitch JA. J Urol. 2001 May;165(5):1510-3

  12. Why Does Varicocelectomy Improve the Abnormal Semen Parameters? • 68 infertile men • Seminal plasma levels of two ROS and six antioxidants on the day prior to varicocelectomy • Same parameters were measured again 3 and 6 months post-operatively. • concluded that varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. • Conclusion: Varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Mostafa T, Department of Andrology, Faculty of Medicine, Cairo University Int J Androl. 2001 Oct;24(5):261-5.

  13. Varicocele: a bilateral disease • 286 infertile men • Physical examination, contact thermography, Doppler sonography, and venography of both testes. • 88.8% bilateral • Mean sperm concentration increased from 6.12 +/- 1.02 to 21.3 +/- 1.69 million/mL • mean sperm motility from 16.81 +/- 1.51 to 35.90 +/- 1.41% • mean sperm morphology from 9.75 +/- 0.85 to 16.92 +/- 1.17%. • Pregnancy rate was 43.5% • This may suggest that we should consider varicocele a bilateral disease Gat Y. Fertil Steril. 2004 Feb;81(2):424-9.

  14. Is assisted reproduction the optimal treatment for varicocele-associated male infertility? A cost-effectiveness analysis. • The cost per delivery with ICSI was found to be $89,091 • The cost per delivery after varicocelectomy was only $26,268 • The average published U.S. delivery rate after one attempt of ICSI was only 28%. whereas a 30% delivery rate was obtained after varicocelectomy. • CONCLUSIONS: Specific treatment of varicocele-associated male factor infertility with surgical varicocelectomy is more cost-effective than primary treatment with assisted reproduction. Schlegel PN. Urology. 1997 Jan;49(1):83-90

  15. Varicocele & Azoospermia • 4.3-13.3%

  16. Consideration of sterility; subfertility in the male • Interestingly, the first study on the importance of varicocelectomy to male infertility (Tulloch, 1952 ) reported spontaneous pregnancy after varicocele repair in an azoospermic man Tulloch, W.SEdinb. Med. J. 1952 , 59, 29–34.

  17. Results of ligation of internal spermatic vein in the treatment of infertility in azoospermic patients. • 10 azoospermic patients • 2 pregnancies Mehan DJ. Fertil Steril. 1976 Jan;27(1):110-4.

  18. Inguinal Varcocelectomy in Azoospermic patients • 13 azo inguinal varicocelectomy • Induction of spermatogenesis was achieved in 3 (23%) patients • Two of them had hypospermatogenesis and one had maturation arrest at spermatid stage • No pregnancies by natural intercourse Cakan M. Arch Androl. 2004 May-Jun;50(3):145-50

  19. Sclerotherapy for Varicocele in Azoospermic patients • 14 Azo sclerotherapy • 7/14 produced sperms • Sperm con 3.1 ± 1.2 × 106/mL • Mean sperm: 2.2 ± 1.9% • mean sperm normal morphology: 7.8 ± 2.2% • 2 pregnancies Poulakis V. Asian J Androl. 2006 Sep;8(5):613-9.

  20. Embolization of Varicocele • 32 men with azoospermia • Improved in 18/32: • sperm concentration in the ejaculate 3.81±1.69 x 106/ml • mean sperm motility: 1.20±3.62% • mean sperm morphology: 8.30±2.64 • Nine pregnancies (26%) • Four (12%) unassisted • Five (15%) by ICSI Gat Y. Human Reproduction 2005 20(4):1013-1017

  21. 27 azoospermia microsurgical varicocelectomy Induction of spermatogenesis was achieved in nine men (33.3%) Sperm conc 1.2 x 10(6)/mL to 8.9 x 10(6)/mL Motility 24% to 75.7%, One patient with maturation arrest established pregnancy Five relapsed into azoospermia 6 months after the recovery of spermatogenesis Is the Effect Durable? Pasqualotto FF, Fertil Steril. 2006 Mar;85(3):635-9.

  22. How long does it take for the sperms to appear? • 17 azo microsur • Spermatozoa in the ejacultae 47% (8/17) • Only 35% (6/17) of them had motile sperm • Mean time for appearance of spermatozoa in the ejaculates was 5 months (3 to 9 months). Esteves SC. Int Braz J Urol. 2005 Nov-Dec;31(6):541-8.

  23. Predictors of Success

  24. Response to varicocelectomy in oligospermic men with and without defined genetic infertility. • 33 men with infertility & varicocele • 7 has coexisting genetic infertility: • Abnormal karyotype in 4 • Y chromosome microdeletion in 3 • 26 No defect • Same semen parameters • All had varicocelectomy • 54% VS 0% improvement • CONCLUSIONS: From this early experience, men with varicocele and genetic lesions appear to have a poorer response to varicocele repair than men without coexisting genetic lesions.

  25. Paternity after varicocelectomy: preoperative sonographic parameters of success. • What are the sonographic findings that could predict the outcome of varicocele repair in the treatment of male infertility? • 107 patients with varicocele. • CONCLUSIONS: The best preoperative sonographic parameters of success of varicocele repair are: • The presence of normal-sized testes • Clinically palpable veins • Bilateral varicocele Donkol RH. J Ultrasound Med. 2007 May;26(5):593-9.

  26. Relationship between varicocele size and response to varicocelectomy. • grade 1--small (22 patients) • grade 2--medium (44) • grade 3--large (20) • Sperm count, per cent motility, per cent tapered forms were measured preoperatively and postoperatively. • Conclusion: infertile men with a large varicocele have poorer preoperative semen quality but repair of the large varicocele in those men results in greater improvement than repair of a small or medium sized varicocele. Goldstein M.J Urol. 1993 Apr;149(4):769-71

  27. Azoospermia: Predictors of Success • FSH • Histology

  28. FSH • Preoperative FSH levels between men who did (14.8 ± 3.1 IU/L) and did not (19.4 ± 3.8 IU/L) show improvement in semen parameters after sclerotherapy were not significantly different Czplick M. Arch Androl. 1979;3(1):51-5

  29. Histology • Germinal Aplasia • Maturation arrest at spermatocyte stage • Hypospermatogenisis • Maturation arrest at spermatid stage

  30. ….continue: predectors of success • 13 Azoospermic patients • Age • Preoperative sex hormones • Unilaterl VS Bilateral • Varicocele grade • Hypospermatogenesis and late maturation arrest No association Arch Androl. 2004 May-Jun;50(3):145-50

  31. Subclinical Varicocele • subclinical in 73 patients • Clinical in 66 patients, based on palpation in addition to ultrasonography. • Conclusion: ligation of varicoceles detected using Doppler ultrasonography, whether palpable or not, results in an increase in sperm concentration and motility. Pierik FH, Rotterdam, The Netherlands. Int J Androl. 1998 Oct;21(5):256-60.

  32. 76 underwent varicocele repair • Improvement: Clinical VS subclinical:67% VS 41% • But: Equal number were worse postoperatively and, thus, mean sperm count was unchanged for the group with subclinical varicocele • Conclusion: The results of our study suggest that subclinical varicocelectomy is of questionable benefit. Jarow JP North Carolina, USA. J Urol. 1996 Apr;155(4):1287-90

  33. Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm. • 350 patients: • Ejaculated sperm • Epididymal • Testicular CONCLUSION: The fertilizing ability of sperm in ICSI is highest with normal ejaculated semen and lowest with sperm extracted from a testicular biopsy in non-obstructive azoospermia. Aboulghar M. Fertil Steril. 1997 Jul;68(1):108-11

  34. Conclusion • Varicocele may cause any variation of severity in spermogram including azoospermia. • The treatment of varicocele may significantly improve spermatogenesis and renew sperm production. • Adequate treatment may spare the need for TESE as preparation for ICSI in >30% of azoospermic patients. • Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele is an effective medical adjunct for IVF units prior to the treatment. • In men with spermatogenic failure, freshly ejaculated sperm are easier to use, and fertilization ability in ICSI is higher with normal semen than with sperm retrieved by TESE

  35. Thank You