Factors influencing the variable incidence of Y chromosome microdeletions in infertile patients

Division of Andrology, Internal Medicine Department, University of Catania Medical School, Ospedale Garibaldi, Piazza S. Maria di Gesù, 95123 Catania, Italy

The article by Simoni et al. (1998) which summarized the published studies on the presence of Y chromosome microdeletions in infertile male patients was very interesting. By reviewing this literature, the authors attempted to answer the following three fundamental questions on this continuously evolving issue: (i) what is the real frequency on microdeletions in infertile patients?; (ii) which microdeletions are clinically relevant?; and (iii) in which patients are molecular diagnosis indicated? We think that all can easily agree with the authors that only patients with a sperm concentration <5x10⁶/ml should be screened for the presence of Y chromosome microdeletions, regardless of the concomitant presence of varicocele (as also suggested by our own personal experience), and that only discrete microdeletions never found in normal controls should be assigned a causative role in the pathogenesis of oligoazoospermia (Pryor and Roberts, 1998). However, it is much more difficult to have a common view on the incidence of patients exhibiting microdeletions of the Y chromosome. As pointed out by Simoni et al. (1998), this percentage varies among studies ranging from 1% (van der Ven et al., 1997) to 37.5% (Foresta et al., 1997). Albeit a different frequency of microdeletions in the various populations cannot be excluded, it is our opinion that at least two other factors may account for this variability. First there are no standardized selection criteria of the sample group. For example, the percentage of microdeletions in azoospermic patients has been reported to be 23% in one study (Pryor et al., 1997) and 37.5% in another (Foresta et al., 1997). This because the latter includes a highly selected group of azoospermic patients with a more severe testicular damage (presence of Sertoli cell-only syndrome). Second, infertile patients with normal sperm count may be included. An example of this is the study by Pryor et al. (1997) which reported the presence of microdeletions in 7% of infertile men (14/200). This led these authors to conclude that only a small proportion of men with infertility have Y chromosome microdeletions. However, a closer look at their data revealed that the `infertile group' included 102 normozoospermic subjects who should have been excluded since Y chromosome microdeletions are responsible for a quantitative, but not qualitative, spermatogenetic decline. Recalculating the data with this adjustment, the percentage of microdeletions rises to 13.3%, while the percentage of microdeletions in patients with idiopathic infertility reaches 17% instead of the reported 9.8%. We therefore suggest a more critical evaluation of the data published and propose to avoid the use of the term infertile men, which may be misleading, and to report the sperm concentration output and a complete andrological evaluation of the cases enrolled. Certainly, normozoospermic infertile patients should not be screened for azoospermia factor nor included in the sample group.

Notes

¹ To whom correspondence should be addressed

Previously displayed on Webtrack 44 on 26 November,1998

References

Foresta, C., Ferlin, A., Garolla, A. et al. (1997) Y-chromosome deletions in idiopathic severe testiculopathies. J. Clin. Endrocrinol. Metab., 82 1075–1080.[Abstract/Free Full Text]

Pryor, J.L. and Roberts, K.P. (1998) Principles of sequence-tagged site selection in screening for Y deletions. Hum. Reprod., 13, 1768.[ISI][Medline]

Pryor, J.L., Kent-First, M., Muallem, A. et al. (1997) Microdeletions in the Y chromosome of infertile men. N. Engl. J. Med., 336, 534–539.[Abstract/Free Full Text]

Simoni, M., Kamischke, A. and Nieschlag, E. (1998) Current status of the molecular diagnosis of Y-chromosomal microdeletions in the work-up of male infertility. Hum. Reprod., 13, 1764–1768.[Free Full Text]

van der Ven, K., Montag, M., Peschka, B. et al. (1997) Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection. Mol. Hum. Reprod., 3, 699–704.[Abstract]