Abstract
BACKGROUND: The relationship between the immune system and embryo implantation is intricate and not yet fully understood. Although a genetically normal (euploid) embryo is essential, successful implantation also relies on carefully regulated immune responses that promote tolerance and prevent rejection. The main objective of this study was to examine the paternal levels of the immunoregulatory factors HLA-G, transforming growth factor (TGF)-ß and interleukin (IL)-6 and to investigate possible correlations with other semen parameters, age and pregnancy outcome of the female partner. METHODS: Seminal plasma samples from 225 men were collected from 2022 to 2025, divided into four groups (live birth, biochemical pregnancy, abortion, no pregnancy) and determined for immunological profiling using commercial HLA-G, TGF-ß and IL-6 enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: SHLA-G levels were significantly lower in the live birth group compared to biochemical pregnancies (p < 0.001) non-pregnancies (p < 0.001) and in abortions compared to non-pregnancies (p = 0.004). TGF-β levels were reduced in all pregnancy-related groups versus non-pregnancies (p < 0.001). IL-6 levels were lower in biochemical pregnancies compared to non-pregnancies (p = 0.017). Absolute HLA-G levels were lower in live births (p < 0.001) and were reduced in abortions (p = 0.004) compared to non-pregnancies. Absolute TGF-ß values were significantly lower in the live birth group (p < 0.001) compared to non-pregnancies. Absolute TGF-β and IL-6 levels were also decreased in biochemical pregnancies compared to non-pregnancies (p < 0.001 and p = 0.03, respectively). CONCLUSION: Our findings show that seminal plasma levels of HLA-G, TGF-β and IL-6 differ significantly among pregnancy outcome groups in ART cycles, underlining a potential role of these immunological factors in influencing reproductive success. These results highlight the importance of seminal immunological profiling as a possible predictive tool for ART outcomes and warrant further investigation in larger cohorts.