Effect of Inflammation on Sperm Quality in Men with Immune-Mediated Inflammatory Diseases: A Secondary Analysis

We will study how chronic inflammation affects male fertility, particularly in men with immune-mediated inflammatory diseases (IMIDs). These are conditions where the body’s immune system attacks healthy tissue, leading to long-term inflammation (which is the body’s natural response to injury or infection, but when it becomes long-lasting, it can damage healthy tissues). Examples include inflammatory bowel disease (IBD, a group of conditions that cause ongoing swelling and irritation in the digestive tract) and certain types of arthritis (which refers to diseases that cause pain, swelling, and stiffness in the joints). Millions of people around the world live with IMIDs, and while their impact on overall health is well known, much less is understood about how they may affect reproductive health in men.

Previous research has mostly focused on whether medications used to treat IMIDs harm sperm production. However, there is growing concern that the diseases themselves—and the inflammation they cause—may also reduce fertility, even without the influence of medication. Early studies in animals and laboratory settings suggest that inflammation may interfere with the cells responsible for producing and supporting sperm, and may also damage the protective barrier inside the testicles. This could lead to lower sperm count, poor sperm movement, abnormal sperm shape, or reduced volume of semen.

Understanding whether disease activity itself affects semen quality is important. If we can identify a clear link, it would help doctors give better reproductive advice to men of reproductive age who have IMIDs. It may also lead to new strategies to help preserve fertility in these patients before their condition worsens or treatment begins.

To explore this question, we will use data from two major clinical trials known as the MANTA and MANTA-RAy studies. These trials were originally designed to test whether a medicine called filgotinib affects sperm health in men with active IBD or certain rheumatic (joint-related) diseases. The participants in these studies had their semen quality measured at the beginning of the trial, along with detailed information about their disease severity and inflammation levels—specifically, a protein in the blood called C-reactive protein (CRP) that rises when there is inflammation.

We will analyze this existing data to look for patterns between inflammation, disease activity, and semen quality. By doing so, we aim to improve understanding of how these diseases impact fertility and support more informed care for patients.