Abstract
Background: Latent Toxoplasma gondii infection is highly prevalent worldwide and has been linked to adverse reproductive outcomes. However, the immunological mechanisms through which chronic toxoplasmosis may contribute to unexplained female infertility remain poorly understood, particularly regarding cytokine imbalance at the maternal-fetal interface. Objective: To determine whether latent T. gondii infection is associated with altered serum levels of pro-inflammatory (IFN-γ) and anti-inflammatory (IL-4, TGF-β) cytokines in females with unexplained infertility, and to evaluate whether this cytokine profile reflects a Th1-dominant immune imbalance. Methodology: A case-control study was conducted at Fatima Al-Zahraa Hospital, Baghdad, Iraq (February–May 2026). A total of 250 females were enrolled: 150 with unexplained infertility (cases) and 100 healthy fertile controls. All participants were tested for anti-T. gondii IgG antibodies by ELISA and subgrouped accordingly. Serum IFN-γ, IL-4, and TGF-β were quantified using sandwich ELISA. Data were analyzed using independent t-tests and two-way ANOVA. Results: Toxoplasma seropositivity was significantly higher among infertile females (24.0% vs. 12.0%; OR=2.32, P=0.018). Seropositive infertile females exhibited significantly elevated IFN-γ (45.39±9.76 vs. 33.54±3.84 pg/mL; P=0.026). Neither IL-4 (P=0.714–0.901) nor TGF-β (P=0.397–0.883) differed significantly across subgroups, indicating failure of compensatory anti-inflammatory regulation. Conclusion: Latent T. gondii infection in females with unexplained infertility is associated with a Th1-dominant immune state that is not counterbalanced by regulatory cytokines, potentially disrupting endometrial receptivity and embryo implantation.