Introduction: Men with complete azoospermia factor C (AZFc) microdeletions may have variable degrees of spermatogenic failure. While some are persistently azoospermic, most intermittently or consistently have sperm in the ejaculate. It has been proposed that these men may experience a temporal decline in semen quality with age. The objective of this study was to assess changes in semen parameters over time among men with complete AZFc deletions. Methods: We retrospectively reviewed 163 men with complete AZFc deletions who were tested at our center from 4/1996 to 7/2022. Of these, 41 had =2 semen analyses performed (SA). ANOVA tests were used to compare mean demographic values between azoospermic, intermittently azoospermic, and non-azoospermic men. Wilcoxon matched-pairs signed rank tests were used to compare initial and final semen analyses. Results: In total, 179 SAs were reviewed. The mean number of SAs per patient was 4.4 ± 2.2. The mean time between each SA was 189.6 ± 420.0 days, and the mean time between the first and last SA was 638.9 ± 850.9 days. Of 41 men, 13 (32%) were azoospermic, 9 (22%) intermittently azoospermic, and 19 (46%) were non-azoospermic. Of the non-azoospermic men, most (n=14, 73.7%) had severe oligospermia ( <1 million/mL). Of 9 men with intermittent azoospermia, most had an increase in sperm concentration (n=8, 89%), total sperm count (TSC) (n=8, 89%), and total motile sperm count (TMSC) (n=6, 67%) between the first and last SA. Similarly, most non-azoospermic men also had an increase in sperm concentration (n=12, 63%), TSC (n=11, 58%), and TMSC (n=11, 58%). In comparing semen parameters, men with intermittent azoospermia had an increase in sperm concentration (p=0.0078) and TSC (p=0.0078) between the first and last SA, but no change in TMSC. There was no difference in concentration, TSC, or TMSC over time for non-azoospermic men. While non-azoospermic men were older (mean: 37.0 +/- 5.6 years; p=0.004) versus intermittently azoospermic (mean: 33.4 +/- 3.3 years) or azoospermic men (mean: 30.3 +/- 5.6 years), there were no differences in baseline testosterone (p=0.24), baseline FSH (p=0.31), or testis size (p=0.17 right, p=0.50 left). Conclusions: In this study, there was no significant decline in sperm concentration, TSC, or TMSC over time for men with complete AZFc deletions; rather, sperm number tended to increase over time. These data suggest that men with AZFc deletions are not at substantive risk of decline in sperm production and do not need to take aggressive early measures for fertility preservation. SOURCE OF Funding: Authors JM and JG are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
