There have been, in recent years, significant changes in the risk assessment for use of the immunomodulatory drugs azathioprine and 6-mercaptopurine (6-MP).
While it was believed only a few years ago that use of these drugs before a planned pregnancy or during the pregnancy itself was associated with a relatively high risk of side effects (miscarriage, premature birth, birth defects), current data and the increased use of azathioprine and 6-MP in other disorders (e.g. organ transplantation, rheumatoid arthritis) have shown that use of these drugs before or during pregnancy is not associated with an increased risk of complications during pregnancy or with birth defects in the child.
There have also been a number of case reports that suggest that patients with inflammatory bowel diseases do not experience an increased risk due to use of azathioprine or 6-MP. Naturally, there can be no 100% guarantee that a given drug will not adversely affect the course of pregnancy. A careful review of the literature also reveals case reports which show a slightly increased rate of pregnancy complications and miscarriages in association with the use of azathioprine or 6-MP. Upon closer examination, however, it becomes rapidly clear that, because of the small number of cases, no statistical conclusions can be made; in addition, other factors, such as an increased disease activity, may be responsible for the negative effects in these patients.
Thus, a consensus has formed in Europe and the United States that azathioprine and 6-MP can be used during pregnancy if medically necessary and, in fact, should be used if other measures fail to control inflammatory activity. The decision on whether azathioprine should be stopped in women planning a pregnancy or whether con-ception should be planned during ongoing azathioprine therapy requires careful consideration of the advantages and disadvantages and comprehensive counseling of the parents. This decision requires a high degree of responsibility and should include a joint interview between the parents, the treating gynecologist and/or family physician, as well as a gastroenterologist with the corresponding experience. There is no indication for pregnancy termination in women who become pregnant while being treated with azathioprine or 6-MP.
Also controversial is the use of azathioprine or 6-MP by the male partner in couples planning a pregnancy. Here, too, extensive experience from transplantation medicine and in patients with rheumatic disorders and inflammatory bowel diseases who were treated with azathioprine or 6-MP prior to or during the period of conception does not reveal any increased risk for pregnancy complications or birth defects. As with women, however, there are also individual case reports in the scientific literature that suggest possible negative effects on pregnancy secondary to azathioprine or 6-MP. Here, too, data is based on a very small number of cases, which precludes statistical evaluation. European and American pharmaceutical regulatory agencies do not currently recommend that males being treated with azathioprine or 6-MP should discontinue therapy prior to a planned conception. Patients desiring maximum safety, however, can be advised to discontinue azathioprine three months prior to a planned conception. In the intervening period, males will produce sperm whose genetic material is not damaged by azathioprine.
Over the past years, we have followed a large number of women and men who have been treated with azathioprine before and during conception and pregnancy. There have been no reported instances of birth defects or pregnancy complications that could be associated with this therapy