AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test

Genetic abnormalities, including partial deletions of the Y-chromosome,are commonly detectable in men with non-obstructive azoospermia(NOA). NOA can be treated using testicular sperm extraction(TESE) with intracytoplasmic sperm injection (ICSI). Recentstudies have shown that the presence of deletions involvingthe AZFc region do not appear to affect the chance of retrievingspermatozoa or have a significant impact on fertilization orpregnancy rates with ICSI. We investigated the effect of Y-chromosomepartial deletions on the chance of sperm retrieval with TESE.Eighty attempts at sperm retrieval were performed using TESEon men who were previously evaluated for Y-chromosome partialdeletions. Y-chromosome analysis was performed using a polymerasechain reaction (PCR)-based technique with 35 sequence-tagged-sites.Of the 80 men, nine (11%) had partial Y-chromosome deletionsdetected. Two azoospermic men with AZFc deletions had successfulsperm retrieval, ICSI and a subsequent clinical pregnancy. Sevenmen had deletions involving the AZFb region (three men had isolatedAZFb deletions, one had AZFa, AZFb and AZFc deleted, and threehad AZFb and AZFc deleted). None of the seven men had spermatozoaextracted by TESE, a result that is significantly differentfrom the overall 64% (47/73) sperm retrieval rate achieved atour centre (P = 0.001). Two men with AZFb deletions had cellsconsistent with round spermatids identified and injected intooocytes without effecting any normal fertilizations. Althoughpreliminary, these results suggest that the presence of an AZFbdeletion is a significantly adverse prognostic finding for TESE.Men with AZFb deletions should be apprised of these resultsbefore attempting TESE-ICSI. Alternatives such as donor inseminationor adoption should be considered or therapy delayed until improvedresults with round spermatid injections are likely.