Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood th1/th2 cell ratios

Koji Nakagawa, Joanne Kwak-Kim, Kuniaki Ota, Keiji Kuroda, Michi Hisano, Rikikazu Sugiyama, Koushi Yamaguchi

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29 Citations (Scopus)


Problem: We evaluated the clinical efficacy of immunosuppressive treatment with tacrolimus for repeated implantation failure (RIF) patients who have elevated in T helper (Th1)/Th2 cytokine producing cell ratios. Method of study: This was a prospective cohort study of treatment for RIF patients (n = 42) with elevated peripheral blood Th1 (CD4+/IFN-γ+)/Th2 (CD4+/IL-4+) cell ratios at the Sugiyama clinic between November 2011 and October 2013. Twenty-five patients were treated with tacrolimus (treatment group) and 17 received no treatment (control group). Treatment group received tacrolimus 2 days before embryo transfer and continued until the day of the pregnancy test, for a total of 16 days. The daily dose of tacrolimus (1-3 mg) was determined based on the degree of the Th1/Th2 cell ratio. Results: The clinical pregnancy rate of the treatment group was 64.0%, which was significantly higher than that of the control group (0%) (P < 0.0001). In the treatment group, the miscarriage rate was 6.3%, the live birthrate was 60.0% (P < 0.0001). There was no significant side-effect from tacrolimus in treatment group. No one developed obstetrical complications during pregnancy. Conclusion: An immunosuppressive treatment using tacrolimus improved pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2 ratios.

Original languageEnglish
Pages (from-to)353-361
Number of pages9
JournalAmerican Journal of Reproductive Immunology
Issue number4
Publication statusPublished - 2015 Apr 1



  • IVF
  • Repeated implantation failure
  • Tacrolimus
  • Th1/Th2 ratios

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

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