One hundred fourteen healthy men aged 21 to 46 years with primary male infertility for at least 18 months were studied. Male factor infertility was defined by normal sperm morphology less than 50% using World Health Organization criteria, sperm concentration less than 20 x 106/mL (oligozoospermia), and sperm motility less than 50% (asthenozoospermia).
Reference
Busetto GM, Koverech A, Messano M, Antonini G, De Berardinis E, Gentile V. Prospective open-label study on the efficacy and tolerability of a combination of nutritional supplements in primary infertile patients with idiopathic astenoteratozzospermia. Archivio Italiano di Urologia e Andrologia. 2012; 84: 137-140.
Design
Prospective, open-label study
Participants
One hundred fourteen healthy men aged 21 to 46 years with primary male infertility for at least 18 months were studied. Male factor infertility was defined by normal sperm morphology less than 50% using World Health Organization criteria, sperm concentration less than 20 x 106/mL (oligozoospermia), and sperm motility less than 50% (asthenozoospermia). All participants had hormone levels within normal limits and negative semen culture tests. Participants were excluded if they had a history of cryptorchidism, varicocele, genital tract surgery, autoimmune disease, orendocrine or metabolic disease or if they used drugs or substances known to affect sperm count.
Study Medication and Treatment Protocol
Participants received an oral once-daily antioxidant formula containing 145 mg L-carnitine, 64 mg acetyl-L-carnitine, 250 mg fructose, 50 mg citric acid, 50 µg selenium, 20 mg CoQ10, 10 mg zinc, 90 mg ascorbic acid, 1.5 µg cyanocobalamin, and 200 µg folic acid for 4 months.
Primary Outcome Measures
A semen analysis was performed to assess changes in sperm motility and sperm morphology at baseline and after 4 months of treatment. Secondary objectives were sperm concentration and pregnancy incidence during treatment.
Key Findings
In a comparison of semen parameters at baseline and after 4 months of oral antioxidant treatment, mean progressive sperm motility increased from 18.3% at baseline to 42.1% after treatment, corresponding to a statistically significant improvement in sperm progressive motility (P<0.05). Morphologically normal sperm increased from 32.8% at baseline to 38.4% after treatment (no statistical significance). Seventeen patients achieved pregnancy with their partners during treatment. No adverse events or side effects were reported.
Nutritional supplementation and antioxidant formulas containing carnitines are a safe and effective treatment option for male infertility, especially in improving sperm progressive motility.
Practice Implications
Semen analysis is paramount to the evaluation of infertile couples. The quality of sperm is a measure of both the sperm’s genetic integrity and its capacity for fertilizing an oocyte. Poor sperm quality has been associated with abnormal sperm motility, failure of sperm recognition of the zona pellucida, and inability to complete the processes of fertilization.1 Oxidative stress is one of the most common culprits in the destruction of sperm quality and the impairment of male reproductive health.2-6 Reactive oxygen species (ROS) alter the integrity of spermatozoa DNA and result in DNA fragmentation.7,8 Free radicals also alter sperm function and structure, which impairs all semen parameters. Several studies have demonstrated that sperm motility (namely, sperm flagellar movement) and morphology are particularly vulnerable to the effects of oxidative stress.5,9,10 Mature spermatozoa are enclosed in a polyunsaturated lipid membrane, which is vulnerable to oxidation in the presence of ROS, and it is the destruction of this fatty membrane that results in impaired sperm morphology and motility.5,6 High levels of ROS are not only associated with idiopathic male infertility but are also implicated in impaired pre-implantation embryonic development and an increased rate of early pregnancy loss.11,12
Carnitines, as well as several other antioxidants, have been shown to improve semen parameters.9 Carnitines are concentrated in epididymal sperm, where they mitigate oxidative stress of the polyunsaturated lipid membrane and preserve the cytologic structure of spermatozoa. Carnitine also supports bioenergetics and helps clear out unwanted metabolites of cellular metabolism.13,14 The formula being investigated also contained coenzyme Q10, vitamin C, and selenium, all of which are also known to protect against oxidative stress.15,16 Zinc, vitamin B12, and folic acid completed the formulation by providing key nutrients that have been shown to improve male fertility. Given the social and family consequences of infertility as well as the low cost and tolerability of nutritional supplementation, antioxidant formulas containing carnitines are a safe and effective treatment option for male infertility, especially in improving sperm progressive motility.
1. Kao SH, Chao HT, Chen HW, Hwang TS, Liao TL, Wei YH. Increase of oxidative stress in human sperm with lower motility. Fertil Steril. 2008;89(5):1183-1190.
2. Mahfouz R, Sharma R, Sharma D et al: Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil Steril. 2009;91:805.
3. Agarwal A, Sekhon LH. Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: Is it justified? Indian J Urol. 2011;27(1):74-85.
4. Safarinejad MR, Safarinejad S, Shafiei N. Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo-controlled, randomized study. J Urol. 2012;188(2):526-531.
5. Saleh RA, Agarwal. Oxidative stress and male infertility: from research to clinical practice. J Androl. 2002;23(6):737-752.
6. Aitken RJ. Free radicals, lipid peroxidation and sperm function. Reprod Fertil Dev. 1995;7(4):659-668.
7. Sun JG, Jurisicova A, Casper RF. Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod. 1997;56(3):602-607.
8. Bennetts LE, Aitken RJ. A comparative study of oxidative damage in mammalian sperm. Mol Reprod Dev. 2005;71(7):77-87.
9. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005;84(3):662-671.
10. Moustafa MH, Sharma RK, Thornton J, et al. Relationship between ROS production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility. Hum Reprod. 2004;19(1):129-138.
11. Gandini L, Lombardo F, Paoli D, et al. Study of apoptotic DNA fragmentation in human spermatozoa. Hum Reprod. 2000;15(4):830-839.
12. Baker MA, Aitken RJ, Baker MA, Aitken RJ. Reactive oxygen species in spermatozoa: methods for monitoring and significance for the origins of genetic disease and infertility. Reprod Biol Endocrinol. 2005 Nov 29;3:67.
13. Arduini A. Carnitine and its acyl esters as secondary antioxidants? Am Heart J. 1992;123(6):1726-1727.
14. Bremer J. Carnitine—metabolism and functions. Physiol Rev. 1983;63(4):1420-1480.
15. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009;181(2):741-751.
16. Safarinejad MR. The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. Int Urol Nephrol. 2012;44(3):689-700.