Therapeutic potential of carnitine and N-Acetyl-Cysteine supplementation on sperm parameters and pregnancy outcomes in idiopathic male infertility: A systematic review and meta-analysis of randomized control trials

This systematic review and meta-analysis aimed to evaluate the impact of L-carnitine (LC), L-acetyl-carnitine (LAC), and N-acetyl-cysteine (NAC) on sperm parameters and pregnancy outcomes in men with idiopathic infertility. A comprehensive search was conducted in PubMed, Embase, Scopus, and Google Scholar databases up to January 31, 2024. Of the 2293 initial citations, 109 studies were eligible, and 14 RCTs involving 1453 men were included in the analysis. LC supplementation significantly increased the sperm concentration (MD = 6.85), total motility (MD = 10.41 %), and normal morphology (MD = 1.78 %). LAC supplementation improved total motility (MD = 17.03 %) and forward motility (MD = 13.5 %), whereas LC + LAC supplementation showed no significant effects. Carnitine combinations (CCs) increased sperm count (MD = 16.75) and volume (MD = 0.19 mL), with improved forward motility (MD = 7.70 %). NAC supplementation enhanced sperm concentration (MD = 3.09) and normal morphology (MD = 1.43 %) and volume (MD = 0.61 mL). LC and CC significantly reduced follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Meta-analysis demonstrated significant heterogeneity in many comparisons. LC, CCs, and NAC may improve sperm parameters in idiopathic infertile men, including sperm concentration, motility, morphology, and volume as well as pregnancy outcomes. However, the overall quality of the included studies was low and high heterogeneity was observed. Future well-designed RCTs with longer durations and fixed doses are warranted to confirm these findings and to assess their impact on pregnancy outcomes.