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Editorial Commentary

Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl. 2004 ;25:771–772.[Free Full Text]

Varicocele treatment by means of retrograde embolization of the internal spermatic veins results in a more than threefold increase in the pregnancy rate when compared to that in couples in whom treatment was postponed (Comhaire et al, 1985; Dohle et al, unpublished). The recommended treatment of idiopathic oligozoospermia among patients without elevated gonadotropins is tamoxifen, either in association with testosterone undecanoate or not (Comhaire, 1976; Adamopoulos et al, 2003).

It has become increasingly clear that these treatments are more efficacious in terms of increasing the cumulative pregnancy rates among men with lower sperm concentrations than among those with only moderate oligozoospermia (eg, >10 million/mL). In the latter, it seems to be the functional impairment of spermatozoa rather than their number that is responsible for the decreased fertility. Such patients may benefit from complementary treatment with food supplements and/or anti-inflammatory medication.

Although several studies have evaluated the effect of carnitines on sperm parameters and pregnancy rates, very few address this treatment in a placebo-controlled design. In the present issue, Cavallini et al report the results of a double-blind randomized trial. They demonstrate that treating subfertile patients with low-grade varicoceles or idiopathic oligozoospermia and moderately decreased sperm concentration (average before treatment, 10–12 million/mL) with or without carnitines associated with the nonsteroidal anti-inflammatory drug ([NSAID] cinnoxicam) improves sperm quality and increases fertility. After 3 months of the combined delivery of the NSAID with carnitines, the pregnancy rate increased rather dramatically, suggesting that the effect of treatment was through interference with spermatogenesis itself.

There are some critical notes to be made to the results of this well-designed study. First, the treatment-independent pregnancy rate is lower (approximately 0.3% per couple per month) than that expected in couples with a relatively short duration of infertility (15 months) and moderate degree of sperm deficiency. In fact, such couples are estimated to have a 1.4% probability of conception per month at consultation and a cumulative pregnancy rate of 7.4% after 6 months (Collins et al, 1984; Comhaire, 1987). Second, the success rate among couples treated with carnitines alone is rather high, with an estimated 3.6% pregnancy rate per couple per month. In reviewing the literature on treatment with carnitines (Figure), we found 36 pregnancies among 1560 couples per month, equal to 2.3% per couple per month (Moncada et al, 1992; Vicari and Calogero, 2001; Lenzi et al, 2003; Voliani et al, unpublished). In a pilot double-blind randomized trial (unpublished), we were unable to show any favorable effect of complementary supplementation with carnitines on the outcome of World Health Organization–recommended conventional treatment (Rowe et al, 2000), either with respect to sperm characteristics or pregnancy rates. The most important finding is that NSAID treatment, given in conjunction with carnitines, seems significantly more efficient than carnitines alone, though several studies have failed to detect any effect of NSAIDs by themselves. The authors suggest that the NSAID they have administered is more efficient than other NSAIDs, whereby rectal administration is preferred because of supposedly higher bioavailability in the pelvic region. This may be of importance for the treatment of inflammatory conditions of the pelvic organs, but it seems less relevant with regard to an alleged positive effect on spermatogenesis and increasing the sperm concentration.

View larger version (22K): [in this window] [in a new window]   Therapy with carnitines: pregnancy rates. IOA indicates idiopathic oligoasthenozoospermia; Asth, asthenozoospermia; and MAGI, male accessory gland infection.

Notwithstanding these critical notes, it must be emphasized that the results reported by Cavallini et al are of great interest and should stimulate complementary, preferentially multicenter trials. It is of the utmost importance to further increase the armamentarium of treatment options of subfertile men, particularly in view of the enormous economic cost and the increased health hazards to the offspring generated by techniques of assisted reproduction.

References

Adamopoulos DA, Pappa A, Billa E, Nicopoulou S, Koukkou E, Michopoulos J. Effectiveness of combined tamoxifen citrate and testosterone undecanoate treatment in men with idiopathic oligozoospermia. Fertil Steril. 2003; 80: 914 -920.[Medline]

Cavallini G, Ferraretti AP, Gianaroli L, Giulio B, Giovanni V. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl. 2004;25: 761 -770.[Abstract/Free Full Text]

Collins JA, So Y, Wilson EH, Wrixon W, Casper RF. Clinical factors affecting pregnancy rates among infertile couples. Can Med Assoc J. 1984;130: 269 -273.[Abstract]

Comhaire F. Treatment of oligospermia with tamoxifen. Int J Fertil. 1976; 21: 232 -238.

Comhaire FH. Simple model and empirical method for the estimation of spontaneous pregnancies in couples consulting for infertility. Int J Androl. 1987; 10: 671 -680.[Medline]

Comhaire FH, Kunnen M. Factors affecting the probability of conception after treatment of subfertile men with varicocele by transcatheter embolization with bucrylate. Fertil Steril. 1985; 43: 781 -786.[Medline]

Lenzi A, Lombardo F, Sgro P, Salacone P, Caponecchia L, Dondero F, Gandini L. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril. 2003;79: 292 -300.[Medline]

Moncada ML, Vicari E, Cimino C, Calogero AE, Mongioi A, D'Agata R. Effect of acetylcarnitine treatment in oligoasthenospermic patients. Acta Eur Fertil. 1992; 23: 221 -224.[Medline]

Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA, eds. WHO Manual for the Standardized Investigation, Diagnosis and Management of the Infertile Male. 1st ed. Cambridge, United Kingdom: Cambridge University Press; 2000.

Vicari E, Calogero AE. Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis. Hum Reprod. 2001;16: 2338 -2342.[Abstract/Free Full Text]

This article has been cited by other articles:

				D. A. Adamopoulos, S. Nicopoulou, E. Koukkou, A. Pappa, and E. Billa Responsiveness to Tamoxifen Citrate and Testosterone Undecanoate Is Independent of the Severity of Idiopathic Oligozoospermia J Androl, September 1, 2005; 26(5): 565 - 566. [Full Text] [PDF]

				F. H. Comhaire and A. M. A. Mahmoud Editorial Commentary J Androl, September 1, 2004; 25(5): 771 - 772. [Full Text] [PDF]

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