Lay Summary

Proposal No.  IBD-0173
Principal Investigator:  Uma Mahadevan, M.D.
Applicant Organization:  University of California, San Francisco (U.S.A.)
Project Title:  Genetic damage to sperm following treatment with azathioprine/6-mercaptopurine in men with inflammatory bowel disease 
Period of Award:  January 1, 2006 - February 29, 2008

Men with inflammatory bowel disease (IBD) are usually young and of the age to have children.  As IBD is a chronic disease with no known cure, patients usually have to stay on medication indefinitely to keep their disease under control.  Azathioprine (AZA) and its sister drug 6-mercaptopurine (6MP) are commonly used to keep patients in remission for long periods of time. With the more aggressive medical therapy available, many patients are healthy enough to consider having children.  However, when it comes time to have children, men often worry about the effect these medications will have on their ability to get their partner pregnant and have a healthy child.

Studies in animals suggest that male animals on 6MP/AZA are less able to cause a full-term pregnancy in their female partners.  Their sperm appears normal by basic semen analysis, suggesting that the damage is on a genetic or DNA level.  This study proposes to look for genetic damage to sperm in 50 men with IBD who are on 6MP/AZA and compare the level of damage to the sperm of 50 men with IBD not on 6MP/AZA.  A technique called sperm chromatin structure assay (SCSA), used in male fertility clinics to predict infertility, will be used to determine the level of damage.  The 100 men with IBD also will be compared to healthy, non-IBD patients for whom SCSA data is on file.
This type of research has never been done before in men with IBD.  It will help guide the management of men with IBD who are on 6MP/AZA.  While it is very important to remain on the drug to stay in remission, if a couple is infertile and no other defects are found, stopping 6MP/AZA for a period of time may potentially help them conceive a child.