The effect of vitamin D supplementation and vaginal probiotics on fertility in women with recurrent implantation failure: A randomized clinical trial

Recurrent implantation failure (RIF) is a significant obstacle in assisted reproductive technology, affecting approximately 10 % of couples undergoing in vitro fertilization (IVF). Emerging evidence suggests that vaginal probiotics and vitamin D supplementation may improve reproductive outcomes. This randomized clinical trial evaluated the effects of these interventions on fertility in women with RIF and thin endometrium (<6 mm). A total of 112 women with a history of RIF were randomized into four groups: vaginal probiotics, vitamin D supplementation, a combination of both, or standard IVF treatment (control). The primary outcome was the pregnancy rate, confirmed by beta-hCG testing and ultrasound. Secondary outcomes included changes in Th1/Th2 ratio, natural killer (NK) cell activity, and cytokine profiles. The combination group demonstrated the highest pregnancy rate (46.4 %), which was significantly higher compared with the probiotics ((14.2 %), p = 0.008), vitamin D ((17.8 %), p = 0.002), and control groups ((10.7 %), p = 0.003). Only the combination therapy significantly reduced the Th1/Th2 ratio (p < 0.001) and NK cell activity (p < 0.001), while significantly increasing IL-4 and TGF-beta and decreasing IFN-gamma levels (all p < 0.001). These findings suggest that combined vaginal probiotics and vitamin D supplementation may improve pregnancy outcomes by modulating the immune responses in women with RIF. This dual intervention may represent a promising strategy for enhancing fertility in this population of RIF patients.