O-015 Spontaneous alterations in semen parameters are associated with age, accessory gland function and the FSHB c.-211G&gt;T variant
Authors: Zitzmann M , Schubert M , Sansone A , Kliesch S 
Published: June 2023

Abstract

Study question
Which parameters are associated with spontaneous alterations in semen analysis in infertile men?

Summary answer
Changes in semen parameters are modulated by abstinence time, accessory gland function and fluctuations in FSH serum concentration, which is bound to FSHB c.-211G&gt;T variant.

What is known already
There is a strong within-subject alteration of semen parameters in men with infertility. The WHO therefore recommends two ejaculate analyses. However, it remains unknown in which subgroup variations are likely to occur and which semen parameters are affected.
We assume that in some men with idiopathic infertility, ejaculate parameters may spontaneously change without interventional medication apart from regression to the mean effects. The study aims to identify factors in conventional semen analysis based on the patients’ clinical data, including reproductive hormones like follicle stimulating hormone (FSH), and factors impacting endocrine activity, like the FSHB-211 promoter gene.

Study design, size, duration
In this retrospective longitudinal study we selected 3456 deeply phenotyped men with idiopathic infertility who had visited our centre for fertility workup from 2010-2020. The patients were selected from our well curated database Androbase© for analysis of repeated ejaculate samples.

Participants/materials, setting, methods
Men with idiopathic infertility and at least two ejaculate analyses (70-90 days distance) were included. Exclusion criteria comprised: sperm concentration &lt;1 million/ml, abnormal FSH or low testosterone, bitesticular volume (bTV) &lt;10ml, orchiectomy, cryptorchidism, varicocele testis, oncological disease, genetic findings (i.e. abnormal karyotype, AZF deletions), medication affecting spermatogenesis.
Grouped linear 2-level nested mixed-effect models were applied. Analyzed parameters included: somatic, hormonal (including FSH and FSHB c.-211 variants), and semen parameters (including abstinence time, accessory gland markers).

Main results and the role of chance
Groups were built according to sperm concentration: A (n = 397): ≥1.0 to &lt; 5.0 mill/ml, B (n = 708): ≥5.0 to &lt; 15.0 mill/ml, C (n = 2351): ≥15.0 mill/ml.
A, B and C: changes in ejaculate volume were associated with alterations in total sperm count and motility (p &lt; 0.003). Changes were, controlled for abstinence time (p &lt; 0.001), related to alpha-glucosidase, fructose or zinc (p = 0.005-0.02).
A+B: fluctuations in FSH concentration 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 FSH concentration (p &gt; 0.1).
B: age &lt;50 years (p = 0.007-0.01) and normal bTV (p = 0.008-0.02) were associated with spontaneous increases of sperm concentration, count and motility.
Semen parameters exhibit intra-individual alterations associated with organic, hormonal and genetic variables. Changes are pronounced in younger men with normal bTV and oligo- to almost normozoospermia. The effect is modulated by abstinence time, accessory gland function and fluctuations in FSH concentrations which, in turn, are bound to the FSHB-211 promotor gene polymorphism.

Limitations, reasons for caution
A limitation of our approach is the retrospective nature of the study, which cannot exclude the possibility of bias within the data set.

Wider implications of the findings
Judgement of semen analysis should be based on two semen samples, with abstinence time between 4-5 days. In future clinical trials, abstinence time should be kept constant. It might be investigated if younger men with normal bTV and FSHB c.-211 GT/TT benefit from improving accessory gland function and increasing FSH.

Trial registration number
not applicable