Association between aging and semen parameters: a retrospective study on over 2,500 men

Abstract Study question Is there an association between advancing male age and worsening seminal parameters (If so, is it possible to define an age-threshold for semen quality decline)? Summary answer Only sperm morphology and motility-related parameters exhibited a significant negative association with age, particularly from the age of 40 years. What is known already While the importance of advanced maternal age on reduced fertility and higher reproductive risks is well documented, scarce and controversial are the information regarding the role of aging on male fertility potential. Indeed, growing concerns arise from the trend in the advancing average parenthood age in Western countries. Study design, size, duration A retrospective study was conducted in 11,307 consecutive semen samples obtained from men who attended the Andrology Unit of the University Hospital of L’Aquila, during the period from January 1992 to January 2022 for evaluation of their fertility potential. Participants/materials, setting, methods Semen samples were collected by masturbation into sterile containers after a sexual abstinence of 2-7 days. Total sperm count (TSC) was calculated by multiplying sperm concentration and the volume of the ejaculate, motile sperm concentration (MSC) was calculated by multiplying sperm concentration and progressive motility (%), and the total motile sperm count (TMSC) was calculated by multiplying MSC and volume. Leukocytospermia was defined as > 1x106 peroxidase-positive cells/mL. Main results and the role of chance Three hundred and forty-nine patients with azoospermia or severe oligozoospermia (<5x106 spz/ml) were excluded. Moreover, 8,450 were excluded because they were only subjected to semen analysis without concomitant clinical evaluation. Therefore, 2,508 subjects have been included in the final analysis. Significant inverse correlations were observed between male age and semen volume (p=0.04), total (p<0.0001) and progressive sperm motility (p<0.0001), TMSC (p=0.01), total progressive motile count (p=0.008), and percentage of spermatozoa with normal morphology (p=0.001), but not with sperm concentration (p=0.8) and TSC (p=0.2). After adjustment for abstinence time, smoking, history of genital tract infections, genital trauma, varicocele, cryptorchidism, orchiectomy, and the year the semen analysis, a significant negative association was found for total (p<0.0001) and progressive motility (p=0.0003), TSC (p=0.001), total progressive motile count (p=0.001), and normal morphology (p=0.035). The comparison of seminal parameters among age quartiles revealed that the age group above 40 years was associated with a significant reduction in total and progressive motility, total motile, and total progressive motile count, while the decline in the percentage of normal forms appeared to be earlier. Limitations, reasons for caution The present study did not analyze couple reproductive outcomes. Moreover, since sperm DNA fragmentation was available only for a limited number of subjects, it was not possible to assess its possible association with male aging. Wider implications of the findings In the light of the possible role of oxidative stress in affecting semen parameters in men aged over 40, the optimization of paternal lifestyle combined with targeted antioxidants treatments could be valuable preventive tools in the couple infertility work-up. Trial registration number not applicable