These actions all support the use of carnitine as a possible therapy for selected forms of male infertility, and it has already been proposed for the treatment of conditions involving altered semen parameters [1, 11, 13]. However, the validity of most preliminary studies investigating the role of carnitine administration on male fertility has been questioned, as the lack of a control group made results unreliable.

Since then, several randomized controlled trials assessing the effects of carnitine administration on semen parameters have been published [4, 9, 13, 15, 21]. To the present date, most studies have shown some degree of improvements in subjects undergoing treatment with carnitine, either alone or together with other antioxidants (Table 3.1). However, not all subjects respond equally to treatment: the rationale for the lack of response lies in the baseline conditions of the patient undergoing therapy. Male genital tract infections, including epididymitis, are associated with a marked decrease in seminal plasma carnitine concentration. In these patients, administration of carnitine alone might not have the desired effects, as the antioxidant effects of the treatment might not be enough to prevent further inflammation-related oxidative stress. Therefore, antibiotic treatment should be suggested before administering carnitine [17], as this would improve chances at obtaining better semen parameters. On the other hand, lipid peroxidation might persist despite antibiotic treatment, and patients with leukocytospermia are less prone to respond to treatment with combined L-carnitine and acetyl-L-carnitine despite being asymptomatic [22, 23]. In these subjects, improvements have been reported in terms of vitality only, despite an increase in motility and viability in non-leukocytospermic men.

Combined treatment was also effective in increasing semen quality in selected populations, particularly in groups with worse baseline conditions [13, 15]. This might reflect underlying conditions, including excessive ROS generation, which might be treated by administration of carnitine and its derivatives. Carnitine and acetyl-L-carnitine were administered together with cinnoxicam, a nonsteroidal anti-inflammatory drug, in an experimental study aimed to assess the possible effects of these drugs on male fertility. In both idiopathic and varicocele-associated OAT, despite some negligible side effects, the therapy resulted significantly more effective than L-carnitine/acetyl-L-carnitine alone or than placebo in terms of improvements of sperm concentration, motility, and morphology [7]. Motility seems to be the parameter most frequently improved following administration of carnitine. This has been confirmed even in association with other compounds with antioxidant properties [6], although the association of carnitine and clomiphene citrate resulted in significantly increased sperm motility and concentration [18], suggesting a possible use as a first-line treatment for idiopathic OAT.