Ulcerative Colitis Surgery Triples Infertility Risk in Women

ANN ARBOR, Mich., June 14 - A last-resort surgical treatment for ulcerative colitis triples the risk of infertility for female patients, according to researchers here.

Although infertility has been often reported anecdotally as a complication of colectomy with ileal pouch-anal anastomosis, this study quantifies widely varying estimates, said Peter Higgins, M.D., Ph.D., of the University of Michigan here.

The approval of Remicade (infliximab) for chronic maintenance in moderate to severe ulcerative colitis "has led patients and physicians to closely re-examine the risks and benefits of colectomy in comparison with medical therapy," Dr. Higgins and colleagues reported online in the journal Gut.

To help make informed decisions, the researchers conducted a meta-analysis of eight major studies of ileal pouch-anal anastomosis from 1989 to 2004.

Overall, Dr. Higgins and colleagues reported, the medical infertility rate in those eight studies was 19.9%, while the infertility rate after ileal pouch-anal anastomosis was 50.1%.

However, one study - conducted by researchers at the Cleveland Clinic and published in 2004 - had a higher infertility rate (38%) among medically treated patients than any of the other studies and contributed to highly significant heterogeneity among the studies.

When the Cleveland study was excluded, the researchers reported, the heterogeneity become non-significant.

Among the remaining seven studies, Dr. Higgins and colleagues said, the medical infertility rate was 14.6%, compared with a rate after ileal pouch-anal anastomosis of 48%.

The difference amounts to a relative risk of infertility for ileal pouch-anal anastomosis patients of 3.17, compared with those getting medical management of their colitis. The 95% confidence interval ranged from 2.41 to 4.18.

The researchers were unable to identify any variables that consistently affected risk, they said, "including adhesion barriers, intraoperative lysis of adhesions, pouch type (S versus J), and pouch anti-adhesives."

One of the studies showed that intra-operative transfusion was associated with greater risk of infertility, and another suggested that post- ileal pouch-anal anastomosis infertility "may be largely due to scarring of fallopian tubes" after surgery, the researchers noted.

Both possibilities make sense, Dr. Higgins and colleagues noted. Transfusion may be a proxy for a difficult surgery, rather than directly causing the infertility, while fallopian tube scarring could take place in the same context.

The researchers noted several limitations:

• None of the studies was randomized, opening the door for selection bias. Thus, patients undergoing colectomy may have been more debilitated, resulting in higher baseline fertility impairment.
• Response rates varied from study to study; subjects who blamed the surgery for their infertility may have been more likely to respond.
• Several studies only included women post- ileal pouch-anal anastomosis, and therefore relied on distant recall of events.
• Two studies included an unknown number of women with familial adenomatous polyposis. However, since familial adenomatous polyposis is rare, this likely didn't greatly affect the outcome, the researchers said.