Spontaneous alterations in semen parameters are associated with age, accessory gland function and the FSHB c.-211G>T variant

Background: There is a strong within-subject alteration of semen parameters in men with infertility. However, it remains unknown in which subgroup variations are likely to occur and which semen parameters are affected.

Objective: To evaluate parameters associated with spontaneous alterations in semen analysis.

Patients and methods: We retrospectively selected 3456 men with infertility without known causes affecting spermatogenesis or sperm output for analysis of repeated ejaculate samples. Exclusion criteria comprised sperm concentration <1 million/mL, abnormal follicle-stimulating hormone or low testosterone, and low bitesticular volume (<10 mL). Grouped linear two-level nested mixed-effect models were applied. The analyzed parameters included abstinence time, bitesticular volume, age, accessory gland markers, follicle-stimulating hormone, and FSHB c.-211 variants.

Results: Groups include A (n = 397): ≥1.0 to <5.0 million/mL, B (n = 708): ≥5.0 to <15.0 million/mL, and C (n = 2351): ≥15.0 million/mL. Groups A, B, and C: changes in ejaculate volume were associated with alterations in total sperm count and motility (p < 0.003). Changes were, controlled for abstinence time (p < 0.001), related to α-glucosidase, fructose, or zinc (p = 0.005-0.02). Group A + B: fluctuations in follicle-stimulating hormone level influenced sperm concentration/count (p = 0.004-0.02), albeit only in men with FSHB c.-211 GG (p = 0.007-0.02). T-allele carriers did not show changes in follicle-stimulating hormone levels (p > 0.1). Group B: age <50 years (p = 0.007-0.01) and normal bitesticular volume (p = 0.008-0.02) were associated with spontaneous increases in sperm concentration, count, and motility.

Conclusion: Semen parameters exhibit intra-individual alterations associated with organic, hormonal, and genetic variables. Changes are pronounced in younger men with normal bitesticular volume and oligozoospermia to almost normozoospermia. The effect is modulated by abstinence time, accessory gland function, and fluctuations in follicle-stimulating hormone level, which is bound to FSHB c.-211G>T variant. Judgment of semen analysis should be based on two semen samples, with abstinence times between 4 and 5 days. As a future perspective, it might be investigated whether younger men with normal bitesticular volume who are unable to elicit increases in serum follicle-stimulating hormone (FSHB c.-211 genotype of GT/TT) benefit from improving accessory gland function and increasing follicle-stimulating hormone.