Endocrine Abstracts

Background: Testicular overstimulation is the pursued therapeutic goal when exogenous follicle-stimulating hormone (FSH) is empirically administered to men with idiopathic infertility. Although a robust physiological rationale theoretically supports the FSH use in male idiopathic infertility, useful markers to evaluate its efficacy are still far from being detected. While pregnancy rate remains the strong outcome in couple infertility management, the identification of reliable, and possibly early, markers of therapeutic response to FSH in males is mandatory. Randomized controlled clinical trials (RCTs) on the topic focused, on the seminiferous component, not considering the potential involvement of the testosterone-secreting compartment.

Aim of the study: The evaluation of the potential relationship between testosterone serum levels and semen quality measured through sperm DNA fragmentation (sDF) index before and after FSH administration in male idiopathic infertility.

Methods: A retrospective post-hoc re-analysis was performed on raw data of RCTs in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported among primary and/or secondary endpoints. Additional data regarding couple infertility history, age, anthropometric variables, FSH treatment scheme and semen variables were included in a single dataset.

Results: Two RCTs (Colacurci et al. 2012 and Simoni et al. 2016) were included accounting for 148 patients (median age 37, 25-52 years). After three months of FSH administration, a significant increase was observed in FSH levels (P<0.001), inhibin B (P=0.012), sperm concentration (P=0.003), total sperm number (P=0.021), progressive motility (P<0.001) and normal sperm morphology (P<0.001). Moreover, an overall sDF index reduction was confirmed after treatment (P=0.002). SDF resulted significantly inversely related to sperm concentration both at baseline and after FSH treatment (Rho -0.325, P<0.001 and Rho -0.316, P=0.001, respectively). Interestingly, sDF index after treatment showed a significant inverse correlation with testosterone serum levels (Rho -0.327, P=0.002). Multivariate stepwise linear regression analyses using sDF index as dependent variable identified testosterone as a predictor for sDF index change (P=0.005). Similarly, logistic regression analysis highlighted testosterone and SHBG levels as predictive of sDF reduction after FSH administration (P=0.043 and P=0.005, respectively).

Conclusion: Combining raw data of published RCTs investigating FSH administration to idiopathic infertile men, a significative improvement of conventional semen parameters together with a reduction in sDF were confirmed. Intriguingly, a potential correlation between testosterone serum levels and sDF was highlighted for the first time, opening a completely unexplored way in the identification of potential early predictors of FSH therapy response in male idiopathic infertility.