The Prognostic Value of Y Chromosome Microdeletions Involving the AZFb Region in Testicular Sperm Extraction

Abstract

Objectives: Testicular sperm extraction (TESE) for intracytoplasmic sperm injection (ICSI) is an effective treatment for men with non-obstructive azoospermia. Overall, approximately 35% of these men have no spermatozoa found in their testicular tissue. The success of TESE cannot be predicted based on preoperative hormonal profiles (FSH, testosterone), nor based on testicular volume. Even a prior diagnostic testis biopsy does not absolutely predict the success of TESE, due to the heterogeneous nature of sperm maturation within seminiferous tubules of the testicle. Preliminary data in recent literature suggest a correlation between microdeletions involving the AZFb of the Y-chromosome and the absence of spermatozoa with TESE (Brandell et al., Human Reprod., 1998). We hereby report our expanded experience of the relationship between microdeletions involving AZFb and TESE results in men with non-obstructive azoospermia.Design: A retrospective analysis of azoospermic men who underwent TESE from 1996 to 2000 was performed. The outcomes of men with AZFb microdeletion of the Y-chromosome were analyzed.Materials and Methods: All TESE were performed under local or general anesthesia by one surgeon. TESE were performed with either multiple biopsies or with a single large incision with multiple samples of the seminiferous tubules under microscopic vision (microdissection TESE). The procedures were performed in conjunction with planned in-vitro fertilization cycles with ICSI for the female partner. Y-chromosomal microdeletion was tested in all patients using DNA extracted from peripheral leukocytes with a series of 35 sequence-tagged sites on Yq using polymerase chain reaction.Results: Among 181 patients who undergone TESE, 10 (6%) were found to have microdeletion involving the AZFb regions and 5 of them (3%) have microdeletion in AZFb region only. For men with non-obstructive azoospermia and no detectable deletions of the AZFb region, 114/171 (67%) men had sperm retrieved with TESE, whereas none of the 11 patients with microdeletions involving the AZFb region had sperm found with TESE (p<0.001). The average duration of TESE in patients with deletions involving the AZFb region was 3.5 hours.Conclusions: Genetic studies may provide important prognostic information in the management of patients with severe male infertility, as illustrated by our observation that the presence of an AZFb deletion is a significantly adverse prognostic finding for TESE. When counseling men with AZFb deletions, clinicians should apprise them of these results before attempting TESE-ICSI. Objectives: Testicular sperm extraction (TESE) for intracytoplasmic sperm injection (ICSI) is an effective treatment for men with non-obstructive azoospermia. Overall, approximately 35% of these men have no spermatozoa found in their testicular tissue. The success of TESE cannot be predicted based on preoperative hormonal profiles (FSH, testosterone), nor based on testicular volume. Even a prior diagnostic testis biopsy does not absolutely predict the success of TESE, due to the heterogeneous nature of sperm maturation within seminiferous tubules of the testicle. Preliminary data in recent literature suggest a correlation between microdeletions involving the AZFb of the Y-chromosome and the absence of spermatozoa with TESE (Brandell et al., Human Reprod., 1998). We hereby report our expanded experience of the relationship between microdeletions involving AZFb and TESE results in men with non-obstructive azoospermia. Design: A retrospective analysis of azoospermic men who underwent TESE from 1996 to 2000 was performed. The outcomes of men with AZFb microdeletion of the Y-chromosome were analyzed. Materials and Methods: All TESE were performed under local or general anesthesia by one surgeon. TESE were performed with either multiple biopsies or with a single large incision with multiple samples of the seminiferous tubules under microscopic vision (microdissection TESE). The procedures were performed in conjunction with planned in-vitro fertilization cycles with ICSI for the female partner. Y-chromosomal microdeletion was tested in all patients using DNA extracted from peripheral leukocytes with a series of 35 sequence-tagged sites on Yq using polymerase chain reaction. Results: Among 181 patients who undergone TESE, 10 (6%) were found to have microdeletion involving the AZFb regions and 5 of them (3%) have microdeletion in AZFb region only. For men with non-obstructive azoospermia and no detectable deletions of the AZFb region, 114/171 (67%) men had sperm retrieved with TESE, whereas none of the 11 patients with microdeletions involving the AZFb region had sperm found with TESE (p<0.001). The average duration of TESE in patients with deletions involving the AZFb region was 3.5 hours. Conclusions: Genetic studies may provide important prognostic information in the management of patients with severe male infertility, as illustrated by our observation that the presence of an AZFb deletion is a significantly adverse prognostic finding for TESE. When counseling men with AZFb deletions, clinicians should apprise them of these results before attempting TESE-ICSI.