Inflammatory arthritis includes a group of rheumatic diseases characterized by the inflammation of joints in addition to systemic manifestations. The most ubiquitous types of inflammatory arthritis are psoriatic arthritis (PsA), rheumatoid arthritis (RA), and axial spondyloarthritis (AxSpA) including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) (Luchetti et al., 2017). In the treatment of inflammatory arthritis, conventional therapeutic options, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), are still used. However, a significant paradigm shift in the treatment has been observed in cases resistant to conventional DMARDs, driven by the introduction of biologic DMARDs (bDMARDs). Among these biological agents, anti-TNF (tumor necrosis factor) drugs are highly effective in patients with csDMARDs-resistance due to the high treatment efficiency and the reasonable and manageable side effects that occur (Tanaka, 2021).

Patients with these inflammatory arthritides are mostly followed up during reproductive ages, and therefore, during the course of anti-TNF therapy, serious concerns have been raised from the view of fertility by both physicians and patients (FitzGerald et al., 2021, Van der Woude and van der Helm-van Mil, 2018, Stolwijk et al., 2016). This has pointed out the importance of the safety of anti-TNF therapy in preconception, conception, and during pregnancy.

The data about the usage and effects of anti-TNFs in pregnancy has recently been increasing among female patients. A systematic review and meta-analysis found no significant differences between biologic therapy and the risks of congenital anomalies or preterm birth (Tsao et al., 2020). These findings were further supported by a more comprehensive meta-analysis, which found no significant differences in the frequency of congenital malformations, low birth weight, small for gestational age, miscarriage, or pre-eclampsia associated with biologic use during pregnancy (O'Byrne et al., 2022). Furthermore, bDMARDs do not appear to affect ovarian reserve, as measured by anti-müllerian hormon (AMH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels, supporting their use in women of reproductive age (Scrivo et al., 2022). There is also limited and low-quality evidence with conflicting results regarding the effects of anti-TNF therapy on sperm analysis. While some studies have found no harmful effects on semen quality, spermatogenesis, anti-sperm antibody production, or testosterone levels, others have reported increased risks of reduced sperm motility, abnormal sperm morphology, and significantly decreased sperm counts (Cooley et al., 2020).

However, beyond laboratory findings, real-world reproductive outcomes are essential to comprehensively evaluate the impact of these therapies on fertility. While such data exist for women, our understanding of the effects of anti-TNF use on male fertility and the pregnancy outcomes of their partners remains limited and largely unclear. This highlights a significant gap in the literature, as research has primarily focused on women, leaving the impact on men underexplored. In this study, we aimed to investigate the influence of anti-TNF treatment on male reproductive potential by evaluating the number of pregnancies and pregnancy outcomes in their female partners, as well as the frequency of infertility among couples.