6th Annual BMRP Investigator Meeting - Abstract

Genetic Damage to Sperm Following Treatment with Azathioprine/6-Mercaptopurine (AZA/6MP) in Men with Inflammatory Bowel Disease (IBD)

Uma Mahadevan^1,a, Fernando Velayos¹, Douglas A. Corley³, Yelena Idomsky¹, Donald Evenson⁴, Paul Turek²

¹Departments of Medicine and ²Urology, University of California, San Francisco (U.S.A); ³Department of Medicine, Kaiser Division of Research (Oakland, California, U.S.A.); ⁴Department of Biochemistry, University of South Dakota (Brookings, U.S.A)

Safety of 6MP/AZA exposure during conception in men with IBD is not well studied. Human studies are conflicting and animal studies suggest a decrease in fertility. The aim of this study was to compare rates of genetic damage in sperm among men with IBD exposed and unexposed to 6MP/AZA using sperm chromatin structure analysis (SCSA), an established technique to study male infertility. Flow cytometry is used to define abnormal chromatin structure as an increased susceptibility of sperm DNA to acid-induced denaturation, which reflects DNA breaks and alterations in the quantity of protamines and in composition and level of disulfide groups.

Methods: This prospective pilot study enrolled men with IBD in remission. Corticosteroids, sulfasalazine, other immunomodulators and biologics were not allowed. Demographic data and fertility history were gathered. Disease activity and 6MP metabolite levels were measured. Two semen analyses with strict morphology and SCSA were performed on each patient.

Results: 25 patients were enrolled – 9 not exposed (controls), 16 exposed (cases) to AZA/6MP. All controls had excellent sperm DNA integrity. Among exposed patients there were 11 excellent, 4 good and 3 fair to poor DNA integrity.

Conclusions: Men with IBD on AZA/6MP were numerically more likely to have sperm DNA integrity in the abnormal range, although the numbers enrolled were too small to determine statistical significance. Larger numbers of patients are needed to determine the significance of these findings and the relationship to dose of medication used.

^aPrincipal Investigator