Male infertility is a complex condition influenced by oxidative stress, endocrine dysregulation, and gut-testis axis dysfunction. Emerging evidence highlights the role of gut microbiota in male reproductive health, suggesting that probiotics may improve sperm quality by modulating systemic inflammation and oxidative stress. This study evaluates the efficacy of multi-strain probiotics compared to conventional antioxidant and hormonal therapies in men with idiopathic oligoasthenoteratozoospermia (OAT).

A prospective, randomised, double-blind controlled trial was conducted on 150 infertile men diagnosed with OAT per WHO 2021 criteria. Participants were randomised into three groups: multi-strain probiotics – Androbiome (n=50; Lactobacillus, Bifidobacterium, and Streptococcus thermophilus, twice daily), Antioxidant combination therapy (n=50; Coenzyme Q10 200 mg/day, L-Carnitine 1 g/day, Zinc, Vitamin C 500 mg/day, Vitamin D3), and Hormonal therapy (n=50; Clomiphene Citrate 25 mg/day orally once daily). Primary outcomes included semen parameters (sperm concentration, motility, morphology, DNA fragmentation index), oxidative stress markers (MDA, TAC), and gut-testis barrier integrity (IL-6, TNF-α, CRP, zonulin). Secondary outcomes included gut microbiome diversity, hormonal changes, pregnancy rates, and treatment tolerability.

After three months, all groups demonstrated significant improvement in semen parameters and oxidative stress markers, but probiotics showed superior efficacy. The probiotic strain resulted in greater increases in sperm concentration, progressive motility (+14.0%), and normal morphology (+10.0%), along with a greater reduction in sperm DNA fragmentation (-17.5%) compared to other groups. Probiotics also showed a decline in oxidative stress and inflammatory markers, correlating with improved gut-testis barrier function. Pregnancy rates at six months post-treatment were highest in the probiotic group (22%). No severe adverse effects were reported, with probiotics demonstrating the highest tolerability.

Probiotic supplementation resulted in overall (15.3%) improvement in sperm quality, oxidative stress reduction, and gut-testis barrier integrity compared to antioxidant and hormonal therapy. These findings suggest that targeting the gut microbiome may represent a novel, non-hormonal therapeutic strategy for idiopathic male infertility. Further studies are warranted to assess its long-term impact on fertility outcomes.