To the Editor:
We read with great interest the article published by Oliva et. al. (1), as our main purpose is to improve semen quality of patients attending our Male Fertility Laboratory where the prevalence of varicocele is high.
Following the experimental design proposed by Nassar el al. (2), we evaluated in 21 normospermic semen samples for the effect of pentoxifylline on protein tyrosine phosphorylation (3), objective motility (Microptic´s Sperm Class Analyser) and total number of sperm with progressive motility recovered after swim-up (4). We found no significant difference in protein tyrosine phosphorylation between treated and control groups. The use of pentoxifylline generates, in our experience, significant differences in objective motility parameters at basal time, i.e: hyperactivity (5.9±0.5 vs. 7.8±0.8 %), curvilinear velocity (53.8±1.4 vs. 58.8±2.3 µm/s), and amplitude of lateral head displacement (2.2±0.05 vs 2.4±0.08 µm), thereby improving the number of progressively motile sperm after swim-up (Wilcoxon test; p<0.05).
If we analyze each particular case, only 57% of the samples improved motility from a mathmatical point of view. Focusing on a program of assisted reproduction, at least 5 million progressive motile sperm are needed for intrauterine insemination outcome (5). From a clinical point of view, only four of our patients overcame this barrier with pentoxifylline (19%). Taking into account the latest literature documenting that assisted reproduction technologies can be associated with poor obstetric and perinatal outcomes and an increase in congenital malformations, more preterm deliveries and low birth weight in single pregnancies, more obstetric complications and more congenital malformations (9.7% vs. 4.3% P=0.046)(6), we consider that the oral administration of the drug proposed by Oliva et al is a better option for our patients.
In spite of that, we have some concerns regarding this work. Although in the abstract the authors outline the effect of the drug on the improvement of sperm morphology, in the text they refer to a slight increment in sperm motility after twelve weeks of treatment. We believe that these data are negligible when considering the motility before treatment. As the authors say, the treatment effect is mainly circumscribed to sperm morphology, although the experimental design should be re-evaluated to elucidate the real effect of pentoxifylline oral administration. In our opinion, a control group is needed, as in this paper it is not clear if the benefit reported is related to pentoxyfylline or to the other antioxidants (zinc and folic acid) that were also administered. The aim of our suggestion is to avoid the potential adverse side effect of pentoxifylline as an inducer of hypotension in case the usefulness of the drug is not certainly proved.
Gabriela Ruth Mendeluk, Ph.D.
Patricia H. Chenlo, M.D.
Melba Sardi-Segovia, M.D.
Susana Curi, M.D.
Julia Ariagno, M.D.
Herberto Repetto, M.D.
Mercedes N Pugliese, M.D.
Luis A Palaoro, Ph.D.
Laboratory of Male Fertility
Department of Clinical Biochemistry
Faculty of Pharmacy and Biochemistry
University of Buenos Aires
Buenos Aires, Argentina
1. Oliva A, Dotta A, Multigner L. Pentoxifylline and antioxidants improve sperm quality in male patients with varicocele. Fertil Steril 2009; 91(4 Suppl): 1536-39.
2. Nassar A, Mahony M, Morshedi M, Srisombut C, Oehninger S. Modulation of sperm tail protein tyrosine phosphorylation by pentoxifylline and is correlation with hyperactivated motility. Fertil Steril 1999; 71(5): 919-23.
3. Mendeluk G, Sardi-Segovia L, Chenlo P, Pugliese M, Repetto H, Curi S, Ariagno J, Prentki Santos E, Paez P, Passanante E, Palaoro L Assessment of human sperm protein tyrosine phosphorylation by immunocytochemistry in a clinical andrology laboratory. Preliminary data. Biotech Histochem. 2009; 7:1-8.
4. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge University Press, 4th edition 1999
5. Abdelkader AM, Yeh J. The potential use of intrauterine insemination as a basic option for infertility: a review for technology-limited medical settings.Obstet Gynecol Int. 2009; 584837.
6. Sebastiani G, Pertierra Cortada A, Vidal Sordé E, Figueras Aloy J, Balasch Cortina J
Factors associated with assisted reproduction technologies and neonatal outcomes.An Pediatr (Barc). 2009; 70(4):323-32.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2010.03.001
The authors declined to respond to this letter.