Abstract
Varicocele is the most common clinical finding in infertile men but controversy continues to surround the utility of its treatment. An increased response of FSH to gonadotrophin-releasing hormone testing has been described in patients with varicocele, while the co-influence of Yq chromosome microdeletions in the infertility associated to this pathology is still under investigation. We studied 30 patients with first- and second- grade varicocele, 15 idiopathic oligozoospermic men and 21 age-matched healthy controls. All subjects underwent testicular Doppler ultrasonography, semen analysis, gonadotrophin-releasing hormone testing and baseline blood sampling for total and free testosterone, PRL, 17β-estradiol, SHBG evaluation and Yq chromosome analysis. Apart from FSH, no difference in baseline hormonal levels was found between the groups. The patients with varicocele showed both an increased basal (p=0.007) and GnRH-induced FSH response (peak and AUC) (p=0.004) in comparison with the controls, while the idiopathic oligozoospermic men had only higher GnRH-induced FSH AUC (p=0.04). In the varicocele group, FSH peaks after GnRH testing correlated positively with the grade of disease (r=0.42, p=0.02) and negatively with sperm count (r=−0.50, p=0.005) and bilateral testis volume (r=−0.52, p=0.005). Sperm count and sperm motility were similarly significantly reduced both in patients with varicocele and in patients with idiopathic oligozoospermia in comparison with healthy controls. Yq chromosome analysis by sequence-tagged site PCR revealed no microdeletion in the AZF regions in any subject studied. Given the quite small number of subjects studied, our overall findings can only prompt us to suggest a possible causal role of varicocele in the impairment of spermatogenesis in our patients. Furthermore, although a genetic co-influence (i.e. Yq microdeletions) does not seem to be involved in the pathogenesis of infertility in men with varicocele and mild to moderate oligozoospermia, genetic screening seems to be advisable, especially in those patients who present a severe impairment of sperm count, as has been suggested by recent literature data.
Similar content being viewed by others
References
De Kretser D.M., Bake W.G. Infertility in men: recent advances and continuing controversies. J. Clin. Endocrinol. Metab. 1999, 84: 3443–3450.
Silber S.J. New concepts in operative andrology: a review. Int. J. Androl. 2000, 23: 66–76.
Fujisawa M., Hayashi A., Imanishi O., Tanaka H., Okada H., Matsumoto O., Kamodono S. The significance of gonadotrophin-releasing hormone test for predicting fertility after varicocelectomy. Fertil. Steril. 1994, 61: 779–782.
Segenreich E., Israilov S., Shmuele J. Evaluation of the relationship between semen parameters, pregnancy rate of wives of infertile men with varicocele, and gonadotropin-releasing hormone test before and after varicocelectomy. Urology 1998, 52: 853–857.
Reijo R., Alagappan R.K., Patrizio P., Page D.C. Severe oligospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet 1996, 347: 1290–1293.
Vogt P.H., Edelmann A., Kirsch S., Henegariu O., Hirschmann P., Ramos C., Hartmann M., Hartschuh W., Meschede D., Behre H.M., Castel A., Nieschlag E., Weidner W., Grone H.J., Jung, A., Engel W., Haidl G. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq 11. Hum. Mol. Gen. 1996, 5: 933–943.
Pryor J.L., Kent-First M., Muallem A., Van Bergen A.H., Nolten W.E., Meisner L., Roberts K.P. Microdeletions in the Y chromosome of infertile men. N. Engl. J. Med. 1997, 336: 534–539.
Krausz C., Quintana-Murci L., Barbaux S., Siffroi J.P., Rouba H., Delafontaine D., Souleyreau-Therville N., Arvis G., Antoine J.M., Erdei E., Taar J.P., Tar A., Jeandidier E., Plessis G., Bourgeron T., Dadoune J.P., Fellous M., McElreavey K. A high frequency of Y chromosome deletions in males with non-idiopathic infertility. J. Clin. Endocrinol. Metab. 1999, 84: 3606–3612.
Seifer I., Amat S., Delgado-Viscogliosi P., Boucher D., Bignon Y.J. Screening for microdeletions on the long arm of the chromosome Y in 53 infertile men. Int. J. Androl. 1999, 22: 148–154.
Moro E., Marin P., Rossi A., Garolla A., Ferlin A. Y chromosome microdeletions in infertile men with varicocele. Mol. Cell. Endocrinol. 2000, 161: 67–71.
Tanner J.M. Growth at adolescence. Blackwell Scientific Publication, Oxford, 1962.
Hargreave T.B. Varicocele. In: Hargreave T.B. (Eds.), Male infertility. Springer Verlag, Berlin, 1994, p. 250.
World Health Organization. World Health Organization laboratory manual for the examination of human semen and semen-cervical mucus interaction, ed. 3. Cambridge University Press, Cambridge, 1992.
Nieschlag E., Hertle L., Fisschedik A., Abshangen K., Behre H.M. Update on treatment of varicocele: counselling as effective as occlusion of the internal spermatic vein. Hum. Reprod. 1998, 13: 2147–2150.
Cayan S., Kadioglu A., Orhan I., Kandirali E., Tefekli A., Tellaloglu S. The effect of microsurgical varicocelectomy on serum follicle stimulating hormone, testosterone and free testosterone levels in infertile men with varicocele. Br. J. Urol. 1999, 84: 1046–1049.
Kim E.D., Leibman B.B., Grinblat D.M., Lipshultz L.I. Varicocele repair improves semen parameters in azoospermic men with spermatogenetic failure. J. Urol. 1999, 162: 737–740.
Ando S., Giacchetto C., Colpi G., Panno M.L., Beraldi E., Lombardi A., Sposato G. Plasma levels of 17-OH progesterone and testosterone in patients with varicocele. Acta Endocrinol. (Copenh.) 1983, 102: 463–469.
World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil. Steril. 1992, 57: 1289–1293.
Plymate S.R., Paulsen C.A., McLachlan R.I. Relationship of serum inhibin levels to serum follicle stimulating hormone and sperm production in normal men and men with varicoceles. J. Clin. Endocrinol. Metab. 1992, 74: 859–864.
Carillo A., Gershbein A., Glassberg K.I., Danon M. Serum inhibin B levels and the response to gonadotrophin stimulation test in pubertal boys with varicocele. J. Urol. 1999, 162: 875–877.
Ma K., Mallidis C., Bhasin S. The role of Y chromosome deletions in male infertility. Eur. J. Endocrinol. 2000, 142: 418–430.
Simoni M., Bakker E., Eyrlings M.C.M., Matthijs G., Moro E., Muller C.R., Vogt P.H. Laboratory guidelines for molecular diagnosis of Ychromosomal microdeletions. Int. J. Androl. 1999, 22: 292–299.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by a 60% MURST grant 1998 to Prof. M.Giusti. DNA samples of the patients are stored at Galliera Genetic Bank, supported by Telethon Italia (grant C42)
Rights and permissions
About this article
Cite this article
Foppiani, L., Cavani, S., Piredda, S. et al. Lack of evidence of a genetic origin in the impaired spermatogenesis of a patient cohort with low-grade varicocele. J Endocrinol Invest 24, 217–223 (2001). https://doi.org/10.1007/BF03343850
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03343850