Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
An immunosuppressive treatment using tacrolimus improved pregnancy outcome of repeated implantation failure patients with elevated Th1/Th2 ratios.
Division of Reproductive Medicine, Sugiyama Clinic, Tokyo, Japan.
Koji
K
Nakagawa
Joanne
J
Kwak-Kim
Kuniaki
K
Ota
Keiji
K
Kuroda
Michi
M
Hisano
Rikikazu
R
Sugiyama
Koushi
K
Yamaguchi
D000026:Abortion, Habitual / Q000276:immunology*; D000022:Abortion, Spontaneous / Q000276:immunology; D000328:Adult; D016022:Case-Control Studies; D010064:Embryo Implantation / Q000276:immunology; D004624:Embryo Transfer / Q000379:methods; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D011446:Prospective Studies; D012098:Reproduction / Q000276:immunology*; D016559:Tacrolimus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D015847:Interleukin-4; D007371:Interferon-gamma; D016559:Tacrolimus
IVF; Th1/Th2 ratios; repeated implantation failure; tacrolimus