The role of probiotics in restoring the Th1 to Th2 ratio in women experiencing recurrent implantation failure; a double-blind randomized clinical trial.

BACKGROUND

Among the complex causes of infertility, Recurrent Implantation Failure (RIF) stands out as a challenging condition. Immunological aberrations are closely implicated in RIF, particularly the imbalance between T helper 1 (Th1) and T helper 2 (Th2) cytokines. Interest in harnessing probiotics to enhance fertility outcomes in RIF-affected women is growing. This study aimed to investigate the potential of probiotics in restoring the Th1 to Th2 ratio and enhancing implantation outcomes in women experiencing RIF.

METHODS

A double-blinded randomized controlled trial enrolled 50 women with a record of at least three RIFs and 50 women with successful pregnancies as a control group in our study. RIF patients were randomly assigned to either the probiotic intervention group (n = 25) or the placebo group (n = 25). The probiotic group administered two tablets per day for 6 months the probiotic tablets that contained prebiotic. At the same time, the placebo group received an identical-looking placebo. Flow cytometry technique was used to evaluate Th1 and Th2 cell frequencies. Gene expression of IL-4, IL-10, TNF-α and IFN-ɣ was analyzed using QRT-PCR. Serum concentrations of IL-4, IL-10, TNF-α and IFN-ɣ cytokines were evaluated using the ELISA technique.

RESULTS

Flow cytometry analysis revealed significantly higher Th1 cell percentages in RIF patients compared to healthy controls, while healthy controls exhibited more significant Th2 cell proportions. Probiotic intervention led to a reduction in Th1 cells and an increase in Th2 cells in RIF patients. ELISA analysis indicated higher proinflammatory and lower anti-inflammatory cytokines compared to controls. After probiotic treatment, TNF-α and IFN-ɣ levels decreased, while IL-10 and IL-4 levels increased in RIF patients. QRT-PCR analysis showed no significant differences in cytokine gene expression between RIF patients before intervention. After probiotic therapy, pro-inflammatory cytokine expression decreased, and anti-inflammatory cytokine expression increased. Placebo treatment resulted in limited changes. Probiotic intervention effectively modulated the Th1 to Th2 ratio in RIF patients, evidenced by reduced Th1 cell percentages, enhanced Th2 cell populations, and cytokine level adjustments. The probiotic intervention improved implantation outcomes in women with RIF, as evidenced by a higher clinical pregnancy rate in the treatment group compared to the placebo group (p = 0.037).

CONCLUSION

These findings highlight the potential of probiotics in restoring immune balance and improving implantation outcomes in women with RIF.