From the AGA Journals

Male IBD medication use doesn’t hamper reproduction, analysis suggests

Understanding the impact of inflammatory bowel disease therapies on fertility and pregnancy outcomes is key toward managing patients with IBD. While there is substantial research on the implications of maternal exposure to IBD medications with reassuring safety data, research in the context of paternal exposure to IBD medications is limited.

Manasi Agrawal, MD, MS, is an Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai. courtesy Icahn School of Medicine at Mount Sinai

Dr. Manasi Agrawal

In this systematic review and meta-analysis, Gubatan and colleagues explore the impact of IBD medications on male fertility and pregnancy outcomes. They report that exposure to biologics (predominantly anti–tumor necrosis factor agents), thiopurines, and methotrexate was not associated with a negative impact on sperm count, sperm motility, sperm morphology, early pregnancy loss, premature birth, or congenital malformations. However, analyses of outcomes with vedolizumab, ustekinumab, and methotrexate were limited by small numbers.

This study represents the largest report summarizing data across diverse populations on the topic with reassuring results. It carries important implications in clinical practice and provides further evidence in support of continuing IBD therapy among male patients through pregnancy planning. Certainly, active IBD in male patients is associated with adverse effects on sperm quality and conception likelihood, and it is important to achieve remission prior to pregnancy planning.

Further research on the impact of paternal exposure to newer biologics, including small molecule drugs, and additional analyses after adjusting for potential confounders will advance the field and provide further guidance in clinical practice.

Manasi Agrawal, MD, MS, is an assistant professor of medicine in the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai, New York. She is a research associate with the Center for Molecular Prediction of Inflammatory Bowel Disease. Aalborg University, Copenhagen. She reports no conflicts.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Medications taken by prospective fathers for inflammatory bowel disease (IBD) do not seem to affect fertility or birth outcomes, according to a systematic review and meta-analysis published in Clinical Gastroenterology and Hepatology.

The effort is the first meta-analysis to assess semen parameters and the risk of adverse outcomes in pregnancy for male patients with IBD who have taken biologics, thiopurines or methotrexate for the condition, the researchers said.

“We provide encouraging evidence that biologic, thiopurine, and methotrexate therapy among male patients with IBD are not associated with impairments in male fertility or with increased risk of adverse pregnancy outcomes,” said the researchers, led in part by John Gubatan, MD, instructor in medicine at Stanford (Calif.) University, who worked with investigators in Copenhagen and Toronto. “Taken together, our data support the safety of continuing biologics, thiopurines, or methotrexate across the reproductive spectrum.”

Questions of fertility and pregnancy outcomes are of particular importance in IBD, since patients are often diagnosed around the time of their reproductive years – about 30 years old for Crohn’s disease and 35 years old for ulcerative colitis. There has been far more research attention paid to female than male reproductive considerations, mainly the health of the fetus when the mother takes biologic therapy for IBD during pregnancy, which has generally found to be safe.

Their search found 13 studies with male IBD patients exposed to biologics, 10 exposed to thiopurines and 6 to methotrexate. Researchers extracted data on sperm count, sperm motility, and abnormal sperm morphology – three metrics considered a proxy for male fertility – as well as early pregnancy loss, preterm birth and congenital malformations.

Researchers found no differences between sperm count, motility or morphology between those exposed and not exposed to biologics, thiopurines and methotrexate, with a couple of exceptions. They actually found that sperm count was higher for thiopurine users, compared with nonusers, and there was only one study on methotrexate and abnormal sperm morphology, so there was no data to pool together for that comparison.

In a subgroup analysis, there was a trend toward higher sperm count in thiopurine users, compared with biologic or methotrexate users, but no differences were seen in the other parameters.

Similarly, there were no significant differences for users and nonusers of these medications for early pregnancy loss, preterm births or congenital malformations, the researchers found.

A prior systematic review suggested that azathioprine might be associated with low sperm count, but this new analysis calls that into question.

“Our results, which demonstrated that thiopurine use among male patients with IBD is associated with increased sperm count, refute this prior finding,” the researchers said. The previous finding, they noted, was only qualitative because the authors didn’t do an analysis to calculate effect size or determine statistical significance.

“Furthermore,” the researchers said, “our study included more updated studies and a greater number of patients.”

The authors disclosed no conflicts of interest.

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