Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology

Causes of azoospermia and their management

P. N. Schlegel

Starr 900, Department of Urology, The New York Presbyterian Hospital, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. email:

Reproduction, Fertility and Development 16(5) 561-572
Submitted: 10 October 2003  Accepted: 30 March 2004   Published: 22 July 2004


Azoospermia may occur because of reproductive tract obstruction (obstructive azoospermia) or inadequate production of spermatozoa, such that spermatozoa do not appear in the ejaculate (non-obstructive azoospermia). Azoospermia is diagnosed based on the absence of spermatozoa after centrifugation of complete semen specimens using microscopic analysis. History and physical examination and hormonal analysis (FSH, testosterone) are undertaken to define the cause of azoospermia. Together, these factors provide a >90% prediction of the type of azoospermia (obstructive v. non-obstructive). Full definition of the type of azoospermia is provided based on diagnostic testicular biopsy. Obstructive azoospermia may be congenital (congenital absence of the vas deferens, idiopathic epididymal obstruction) or acquired (from infections, vasectomy, or other iatrogenic injuries to the male reproductive tract). Couples in whom the man has congenital reproductive tract obstruction should have cystic fibrosis (CF) gene mutation analysis for the female partner because of the high risk of the male being a CF carrier. Patients with acquired obstruction of the male reproductive tract may be treated using microsurgical reconstruction or transurethral resection of the ejaculatory ducts, depending on the level of obstruction. Alternatively, sperm retrieval with assisted reproduction may be used to effect pregnancies, with success rates of 25–65% reported by different centres. Non-obstructive azoospermia may be treated by defining the cause of low sperm production and initiating treatment. Genetic evaluation with Y-chromosome microdeletion analysis and karyotype testing provides prognostic information in these men. For men who have had any factors potentially affecting sperm production treated and remain azoospermic, sperm retrieval from the testis may be effective in 30–70% of cases. Once sperm are found, pregnancy rates of 20–50% may be obtained at different centres with in vitro fertilisation and intracytoplasmic sperm injection.


Bachtell N. E. Conaghan J. Turek P. J. 1999 The relative viability of human spermatozoa from the vas deferens, epididymis and testis before and after cryopreservation. Hum. Reprod. 14 3048 3051 doi:10.1093/HUMREP/14.12.3048 Pubmed Abstract

Belker A. M. Thomas A. J. Jr Fuchs E. F. Konnak J. W. Sharlip I. D. 1991 Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J. Urol. 145 505 511 Pubmed Abstract

Berger R. 1998 Triangulation end-to-side vasoepididymostomy. J. Urol. 159 1951 1953 doi:10.1097/00005392-199806000-00048 Pubmed Abstract

Brandell R. A. Goldstein M. 1999 Reconstruction of the male reproductive tract using the microsurgical triangulation technique for vasoepididymostomy. J. Urol. 161 350 doi:10.1097/00005392-199904020-00404 Pubmed Abstract Suppl.

Brandell R. A. Mielnik A. Liotta D. Ye Z. Veeck L. L. Palermo G. D. Schlegel P. N. 1998 AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum. Reprod. 13 (10), 2812 2815 Pubmed Abstract

Carter S. S. Shinohara K. Lipshultz L. I. 1989 Transrectal ultrasonography in disorders of the seminal vesicles and ejaculatory ducts. Urol. Clin. North Am. 16 (4), 773 790 Pubmed Abstract

Chan P. T. K. Palermo G. D. Veeck L. L. Rosenwaks Z. R. Schlegel P. N. 2001 Testicular sperm extraction combined with intracytoplasmic sperm injection in the treatment of men with persistent azoospermia postchemotherapy. Cancer 92 (6), 1632 1637 doi:10.1002/1097-0142(20010915)92:6<1632::AID-CNCR1489>3.0.CO;2-I Pubmed Abstract

Chang P. L. Sauer M. V. Brown S. 1999 Y chromosome microdeletion in a father and his four infertile sons. Hum. Reprod. 14 2689 2694 doi:10.1093/HUMREP/14.11.2689 Pubmed Abstract

Cornel E. B. Dohle G. R. Meuleman E. J. H. 1999 Transurethral deroofing of midline prostatic cyst for subfertile men. Hum. Reprod. 14 2297 2300 doi:10.1093/HUMREP/14.9.2297 Pubmed Abstract

Costabile R. A. Spevak M. 2001 Characterization of patients presenting with male factor infertility in an equal access, no cost medical system. Urology 58 1021 1024 doi:10.1016/S0090-4295(01)01400-5 Pubmed Abstract

Cram D. S. Ma K. Bhasin S. Arias J. Pandjaitan M., et al. 2000 Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions. Fertil. Steril. 74 (5), 909 915 doi:10.1016/S0015-0282(00)01568-5 Pubmed Abstract

Fischer R. Baukloh V. Naether O. G. J. Schulze W. 1998 The concept of using spermatozoa from cryopreserved testicular tissue for ICSI in the treatment of severe male factor sterility in clinical application. Hum. Reprod. 13 96 97

Goldstein M. Li P. S. Matthews G. J. 1998 Microsurgical vasovasostomy: the microdot technique of precision suture placement. J. Urol. 159 188 190
Pubmed Abstract

Hall S. Oates R. D. 1993 Unilateral absence of the scrotal vas deferens associated with contralateral mesonephric duct anomalies resulting in infertility: laboratory, physical and radiographic findings, and therapeutic alternatives. J. Urol. 150 1161 Pubmed Abstract

Hopps C. V. Mielnik A. Goldstein M. Palermo G. D. Rosenwaks Z. Schlegel P. N. 2003 Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum. Reprod. 18 1660 Pubmed Abstract

Janzen N. Goldstein M. Schlegel P. N. Hariprashad J. Palermo G. D. Rosenwaks Z. 2000 Use of electively cryopreserved microsurgically aspirated epididymal sperm with IVF and intracytoplasmic sperm injection for obstructive azoospermia. Fertil. Steril. 74 696 701 doi:10.1016/S0015-0282(00)01496-5 Pubmed Abstract

Jarow J. P. 1994 Seminal vesicle aspiration in the management of patients with ejaculatory duct obstruction. J. Urol. 152 899 901 Pubmed Abstract

Jarow J. P. 1996 Diagnosis and Management of ejaculatory duct obstruction. Tech. Urol. 2 (2), 79 85 Pubmed Abstract

Johnson M. D. 1998 Genetic risks of intracytoplasmic sperm injection in the treatment of male infertility: recommendations for genetic counseling and screening. Fertil. Steril. 70 397 411 doi:10.1016/S0015-0282(98)00209-X Pubmed Abstract

Jow W. W. Steckel J. Schlegel P. N. Magid M. S. Goldstein M. 1993 Motile sperm in human testis biopsy specimens. J. Androl. 14 194 198 Pubmed Abstract

Kent-First M. Muallem A. Shultz J. 1999 Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome micrudeletion detection. Mol. Reprod. Dev. 53 27 41 doi:10.1002/(SICI)1098-2795(199905)53:1<27::AID-MRD4>3.3.CO;2-N Pubmed Abstract

Kolettis P. N. Thomas A. J. Jr 1997 Vasoepididymostomy for vasectomy reversal: a critical assessment in the era of intracytoplasmic sperm injection. J. Urol. 158 467–470 doi:10.1097/00005392-199708000-00036 Pubmed Abstract

Küpker W. Schlegel P. N. Al-Hasani S. Fornara P. Johannisson R. Sandmann J. Schill T. Bals-Pratsch M. Ludwig M. Diedrich K. 2000 Use of frozen-thawed testicular sperm for intracytoplasmic sperm injection. Fertil. Steril. 73 (3), 453 458 doi:10.1016/S0015-0282(99)00564-6 Pubmed Abstract

Levran D. Ginath S. Farhi J. Nahum H. Glezerman M. Weissman A. 2001 Timing of testicular sperm retrieval procedures and in vitro fertilization–intracytoplasmic sperm injection outcome. Fertil. Steril. 76 2 380 383 doi:10.1016/S0015-0282(01)01908-2 Pubmed Abstract

Malkevich D. A. Miezna M. Nagler H. M. 1994 Patency of ejaculatory ducts after transurethral resection of ejaculatory ducts verified by reflux seen on voiding cystourethrogram. J. Urol. 151 301A. [Abstract]

Marmar J. L. 2000 Modified vasoepididymostomy with simultaneous double needle placement, tubulotomy and tubular invagination. J. Urol. 163 483 486
Pubmed Abstract

Matthews G. J. Goldstein M. 1996 A simplified technique of epididymal sperm aspiration. Urology 47 123 125 doi:10.1016/S0090-4295(99)80397-5 Pubmed Abstract

Matthews G. J. Schlegel P. N. Goldstein M. 1995 Patency following microsurgical vasoepididymostomy and vasovasostomy: Temporal considerations. J. Urol. 154 2070 2073 doi:10.1097/00005392-199512000-00030 Pubmed Abstract

Matthews G. J. Matthews E. D. Goldstein M. 1998 Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia. Fertil. Steril. 70 71 75 doi:10.1016/S0015-0282(98)00108-3 Pubmed Abstract

Nudell D. M. Conaghan J. Pedersen R. A. Givens C. R. Schriock E. D. Turek P. J. 1998 The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of urological outcomes. Hum. Reprod. 13 1260 1265 doi:10.1093/HUMREP/13.5.1260 Pubmed Abstract

Oates R. D. Amos J. A. 1994 The genetic basis of congenital bilateral absence of the vas deferens and cystic fibrosis. J. Androl. 15 1 8 Pubmed Abstract

Ostad M. Liotta D. Ye Z. Schlegel P. N. 1998 Testicular sperm extraction (TESE) for non-obstructive azoospermia: results of a multi-biopsy approach with optimized tissue dispersion. Urology 52 692 697 doi:10.1016/S0090-4295(98)00322-7 Pubmed Abstract

Palermo G. D. Colombero L. T. Rosenwaks Z. 1997 The human sperm centrosome is responsible for normal syngamy and early embryonic development. Rev. Reprod. 2 (1), 19 27 Pubmed Abstract

Palermo G. D. Schlegel P. N. Hariprashad J. J. Ergun B. Mielnik A. Zaninovic N. Veeck L. L. Rosenwaks Z. 1999 Fertilization and pregnancy outcome with intracytoplasmic sperm injection for azoospermic men. Hum. Reprod. 14 741 748 doi:10.1093/HUMREP/14.3.741 Pubmed Abstract

Pasqualotto F. F. Agarwal A. Srivastava M. Nelson D. R. Thomas A. J. 1999 Fertility outcome after repeat vasoepididymostomy. J. Urol. 162 1626 1628 doi:10.1097/00005392-199911000-00014 Pubmed Abstract

Pavlovich C. P. Schlegel P. N. 1997 Fertility options after vasectomy: a cost-effective analysis. Fertil. Steril. 67 133 141 doi:10.1016/S0015-0282(97)81870-5 Pubmed Abstract

Pavlovich C. P. King P. Goldstein M. Schlegel P. N. 2001 Evidence of a treatable endocrinopathy in infertile men. J. Urol. 165 837 841 Pubmed Abstract

Peschka B. Leygraaf J. van der Ven K. Montag M. Schartmann B. Schubert R. van der Ven H. Schwanitz G. 1999 Type and frequency of chromosome aberrations in 781 couple undergoing intracytoplasmic sperm injection. Hum. Reprod. 14 2257 2263 doi:10.1093/HUMREP/14.9.2257 Pubmed Abstract

Prins G. S. Dolgina R. Studney P. Kaplan B. Ross L. Niederberger C. 1999 Quality of cryopreserved testicular sperm in patients with obstructive and nonobstructive azoospermia. J. Urol. 161 1504 1508 doi:10.1097/00005392-199905000-00024 Pubmed Abstract

Pryor J. L. Kent-First M. Muallem A. VanBergen A. H. Nolten W. E. Meisner L. Roberts K. P. 1997 Microdeletions in the Y chromosome of infertile men. N. Engl. J. Med. 336 534 539 doi:10.1056/NEJM199702203360802 Pubmed Abstract

Raman J. D. Schlegel P. N. 2002 Aromatase inhibitors for male infertility. J. Urol. 167 624 629 doi:10.1097/00005392-200202000-00038 Pubmed Abstract

Ron-El R. Strassburger D. Friedler S. Komarovski D. Bern O. Soffer Y. Raziel A. 1997 Extended sperm preparation: an alternative to testicular sperm extraction in non-obstructive azoospermia. Hum. Reprod. 12 1222B 1226B doi:10.1093/HUMREP/12.6.1222 Pubmed Abstract

Ron-El R. Friedler S. Komarovski D. Strassburger D. Schachter M. Soffer Y. Bern O. Kasterstein E. Raziel A. 1998 The fertilizing capability of frozen-thawed motile snd immotile testicular spermatozoa in non-obstructive azoospermic patients. Hum. Reprod. 13 91. [Abstract]

Schlegel P. 1997 Management of ejaculatory duct obstruction. ‘Infertility in the Male’. 3rd Lipschultz L. Howards S. 385 Mosby St Louis, MO, USA.

Schlegel P. N. 1999 a Sperm retrieval techniques for assisted reproduction. Infert. Reprod. Med. Clinic. North Am. 10 3 539 553

Schlegel P. N. 1999 b Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum. Reprod. 14 131 135
doi:10.1093/HUMREP/14.1.131 Pubmed Abstract

Schlegel P. N. 2004 Role of varicocelectomy in men with non-obstructive azoospermia. Fertil. Steril. 81 In press

Schlegel P. N. Goldstein M. 1993 Microsurgical vasoepididymostomy: refinements and results. J. Urol. 150 1165 1168
Pubmed Abstract

Schlegel P. N. Su L. M. 1997 Physiologic consequences of testicular sperm extraction. Hum. Reprod. 12 1688 1692 doi:10.1093/HUMREP/12.8.1688 Pubmed Abstract

Schlegel P. N. Berkeley A. S. Goldstein M. Cohen J. Alikani M. Adler A. Gilbert B. R. Rosenwaks Z. 1994 Epididymal micropuncture with in vitro fertilization and oocyte micromanipulation for the treatment of unreconstructable obstructive azoospermia. Fertil. Steril. 61 895 901 Pubmed Abstract

Schlegel P. N. Shin D. Goldstein M. 1996 Urogenital anomalies in men with congenital absence of the vas deferens. J. Urol. 155 (5), 1644 1648 Pubmed Abstract

Schoor R. A. Elhanbly S. Niederberger C. S. Ross L. S. 2002 The role of testicular biopsy in the modern management of male infertility. J. Urol. 167 197 200 doi:10.1097/00005392-200201000-00044 Pubmed Abstract

Seo J. T. Ko W. J. 2001 Predictive factors of successful testicular sperm recovery in non-obstructive azoospermia patients. Int. J. Androl. 24 (5), 306 310 doi:10.1046/J.1365-2605.2001.00307.X Pubmed Abstract

Sheynkin Y. R. Menendez S. Liotta D. Veeck L. L. Schlegel P. N. 1998 Controlled comparison of percutaneous and microsurgical sperm retrieval in men with obstructive azoospermia. Hum. Reprod. 13 3086 doi:10.1093/humrep/13.11.3086 Pubmed Abstract

Shibahara H. Hamada Y. Hasegawa A. Toji H. Shigeta M. Yoshimoto T. Shima H. Koyama K. 1999 Correlation between the motility of frozen–thawed epididymal spermatozoa and the outcome of intracytoplasmic sperm injection. Ind. J. Androl. 22 (5), 324 328 doi:10.1046/J.1365-2605.1999.00187.X

Silber S. J. 1978 Microscopic vasoepididymostomy: specific microanastomosis to the epididymal tubule. Fertil. Steril. 30 565 571 Pubmed Abstract

Silber S. J. Nagy Z. Devroey P. Tournaye H. Van Steirteghem A. C. 1997 Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure. Hum. Reprod. 12 11 2422 2428 doi:10.1093/HUMREP/12.11.2422 Pubmed Abstract

Su L. M. Palermo G. D. Goldstein M. Veeck L. L. Rosenwaks Z. Schlegel P. N. 1999 Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia: testicular histology can predict success of sperm retrieval. J. Urol. 161 112 116 doi:10.1097/00005392-199901000-00038 Pubmed Abstract

Tash J. A. McGovern J. H. Schlegel P. N. 2000 Acquired hypogonadotropic hypogonadism presenting as decreased seminal volume. Urology 56 (4), 669 doi:10.1016/S0090-4295(00)00716-0 Pubmed Abstract

Tournaye H. Staessen C. Liebaers I. Van Assche E. Devroey P. Bonduelle M. Van Steirteghem A. 1996 Testicular sperm recovery in nine 47XXY Klinefelter patients. Hum. Reprod. 11 1644 1649 Pubmed Abstract

Vogt P. H. Edelmann A. Kirsch S. Henegariu O. Hirschmann P., et al. 1996 Human Y-chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum. Mol. Genet. 5 933 943 doi:10.1093/HMG/5.7.933 Pubmed Abstract

World Health Organization 1999 ‘WHO Laboratory Manual for the Examination of Human Semen and Semen–Cervical Mucus Interaction.’ Cambridge University Press New York, USA.

Rent Article Export Citation Cited By (17)