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Article

Immunomodulatory Effects of Low-Dose Tacrolimus on Pro-Inflammatory and Anti-Inflammatory Cytokines in Women Undergoing Intracytoplasmic Sperm Injection

Rasha Yaseen Jihad ORCID ,  Manal Taha Al-Obaidi ORCID ,  Lubna Amer Al-Anbari ORCID
    Received: 20 July 2026; Revised: 10 August 2026; Accepted: 21 August 2026; Published: 23 September 2026

    Abstract

    Endometrial receptivity is regulated by sex hormones, growth factors, and cytokines. While the anti-inflammatory IL-10 promotes immunological tolerance, overexpression of the pro-inflammatory TNF-α inhibits implantation. Tacrolimus (FK506), a macrolide immunosuppressant, reduces pro-inflammatory cytokines by blocking calcineurin phosphatase. To assess the safety profile of periconceptional low-dose tacrolimus, including side effects and early pregnancy outcomes, and to ascertain how it influences clinical pregnancy rates in women undergoing fresh intracytoplasmic sperm injection (ICSI) cycles. From August 1, 2025, to July 1, 2026, Al-Nahrain University conducted this randomized interventional comparative study. The intervention (tacrolimus 1 mg twice daily from two days previous to embryo transfer until pregnancy testing, continued until 12 weeks if pregnant) and non-intervention groups were equally divided among 80 infertile women (20–40 years old) planned for new ICSI cycles. Serum TNF-α and IL-10 levels were assessed on the day of oocyte retrieval and embryo transfer. Rates of clinical pregnancy were calculated. p < 0.05 was considered significant. The intervention group had significant reductions in TNF-α (0.48 to 0.39, p = 0.003) and increases in IL-10 (0.35 to 0.49, p < 0.001). The Th1/Th2 ratio went back to normal from 2.20 to 0.81 (p < 0.001). Clinical pregnancy rates were greater in the intervention group (45% vs. 25%, p = 0.061). Tacrolimus produced no significant adverse effects and was well tolerated. By reducing TNF-α, boosting IL-10, and reestablishing Th1/Th2 balance, periconceptional low-dose tacrolimus successfully enhances endometrial receptivity with a positive inclination toward improved pregnancy rates. Low dosages of tacrolimus have a favorable safety profile.

    Keywords

    References

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