CONTEXT: An explosive growth in Y chromosome long arm (Yq) microdeletion testing demand for male infertility occurred in the past few years. However, despite the progresses in the biology of this chromosome, a number of molecular and clinical concerns are not supported by definitive data. OBJECTIVE: The objective was to provide information on the type and prevalence of microdeletions in infertile males, indication for testing, genotype-phenotype correlation, sperm aneuploidies, and genetic counseling. DESIGN AND SETTING: We performed a prospective study from January 1996 to December 2005 in an academic clinic. PATIENTS: We studied 3073 consecutive infertile men, of which 625 were affected by nonobstructive azoospermia and 1372 were affected by severe oligozoospermia. Ninety-nine patients with microdeletions are described here. MAIN OUTCOME MEASURES: Yq microdeletions, seminal analysis, reproductive hormones, testicular cytology/histology, and sperm sex chromosomes aneuploidies were used as outcome measures. RESULTS: The prevalence of microdeletions was 3.2% in unselected infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with severe oligozoospermia. Only 2 of 99 deletions were found in men with more than 2 million sperm/ml. No clinical data are useful to identify a priori patients with higher risk of Yq microdeletions. Most deletions are of the AZFc-b2/b4 subtype and are associated with variable spermatogenic phenotype, with sperm present in 72% of the cases. Complete AZFa and AZFb (P5/Proximal P1) deletions are associated with Sertoli cell-only syndrome and alterations in spermatocyte maturation, respectively, whereas partial deletions in these regions are associated with milder phenotype and frequent presence of sperm. Men with AZFc-b2/b4 deletions produce a higher percentage of sperm with nullisomy for the sex chromosomes and XY-disomy. CONCLUSIONS: This extensive clinical research expands the knowledge on genotype-phenotype relationships and confirms that the identification of Yq microdeletions has significant diagnostic and prognostic value, adding useful information for genetic counseling in these patients.

Molecular and Clinical Characterization of Y Chromosome Microdeletions in Infertile Men: A 10-Year Experience in Italy / A., Ferlin; B., Arredi; E., Speltra; C., Cazzadore; R., Selice; A., Garolla; Lenzi, Andrea; C., Foresta. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - STAMPA. - 92:3(2007), pp. 762-770. [10.1210/jc.2006-1981]

Molecular and Clinical Characterization of Y Chromosome Microdeletions in Infertile Men: A 10-Year Experience in Italy

LENZI, Andrea;
2007

Abstract

CONTEXT: An explosive growth in Y chromosome long arm (Yq) microdeletion testing demand for male infertility occurred in the past few years. However, despite the progresses in the biology of this chromosome, a number of molecular and clinical concerns are not supported by definitive data. OBJECTIVE: The objective was to provide information on the type and prevalence of microdeletions in infertile males, indication for testing, genotype-phenotype correlation, sperm aneuploidies, and genetic counseling. DESIGN AND SETTING: We performed a prospective study from January 1996 to December 2005 in an academic clinic. PATIENTS: We studied 3073 consecutive infertile men, of which 625 were affected by nonobstructive azoospermia and 1372 were affected by severe oligozoospermia. Ninety-nine patients with microdeletions are described here. MAIN OUTCOME MEASURES: Yq microdeletions, seminal analysis, reproductive hormones, testicular cytology/histology, and sperm sex chromosomes aneuploidies were used as outcome measures. RESULTS: The prevalence of microdeletions was 3.2% in unselected infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with severe oligozoospermia. Only 2 of 99 deletions were found in men with more than 2 million sperm/ml. No clinical data are useful to identify a priori patients with higher risk of Yq microdeletions. Most deletions are of the AZFc-b2/b4 subtype and are associated with variable spermatogenic phenotype, with sperm present in 72% of the cases. Complete AZFa and AZFb (P5/Proximal P1) deletions are associated with Sertoli cell-only syndrome and alterations in spermatocyte maturation, respectively, whereas partial deletions in these regions are associated with milder phenotype and frequent presence of sperm. Men with AZFc-b2/b4 deletions produce a higher percentage of sperm with nullisomy for the sex chromosomes and XY-disomy. CONCLUSIONS: This extensive clinical research expands the knowledge on genotype-phenotype relationships and confirms that the identification of Yq microdeletions has significant diagnostic and prognostic value, adding useful information for genetic counseling in these patients.
2007
01 Pubblicazione su rivista::01a Articolo in rivista
Molecular and Clinical Characterization of Y Chromosome Microdeletions in Infertile Men: A 10-Year Experience in Italy / A., Ferlin; B., Arredi; E., Speltra; C., Cazzadore; R., Selice; A., Garolla; Lenzi, Andrea; C., Foresta. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - STAMPA. - 92:3(2007), pp. 762-770. [10.1210/jc.2006-1981]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/74562
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