Analysis of early meiotic events and aneuploidy in nonobstructive azoospermic men: a preliminary report

Objective: To study the events of spermatogenesis in azoospermic men by examining meiosis I spermatocytes and postmeiotic spermatozoa. Design: A preliminary analysis of synaptonemal complex (SC), recombination, and chromosomal constitution (meiotic and postmeiotic) in testicular tissue. Setting: Academic research environment. Patient(s): Three men with nonobstructive azoospermia and one fertile man (vasectomy reversal: control) who underwent testicular sperm extraction in preparation for intracytoplasmic sperm injection (ICSI). Intervention(S): Testicular tissue specimens were processed by immunofluorescence, analysis with antibodies against proteins associated with SC and recombination events. Fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was done on spermatocytes in prophase I and on postmeiotic spermatozoa. Main Outcome Measure(s): SC formation and recombination in meiosis I, aneuploidy. Result(S): The number of autosomal recombination foci in each patient was not statistically significantly different from control. The frequencies of XY bivalents with at least one recombination focus were statistically similar in the patients and control (74.2% vs. 82.6%, respectively). All observed cells in pachytene had normal XY constitutions. In spite of this, the rate of sex-chromosome aneuploidy in spermatozoa was statistically significantly higher in the patients compared with the control (1.89% vs. 0.83%). Conclusion(S): The combination of immunocytologic technology with FISH can add a level of precision in etiologic investigations of severe male factor infertility: men can have normal pairing and recombination but still yield aneuploid spermatozoa.