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The Effect of Vitamin D Supplementation and Vaginal Probiotics on Fertility in Women With Recurrent Implantation Failure: A Randomized Clinical Trial Publisher Pubmed



Badihi E1 ; Sharifi P2 ; Moradi A3 ; Kamrani A1, 4 ; Hassanzadeh A5 ; Soltanizangbar MS1, 4 ; Parsania S1 ; Afandideh F1 ; Ahmadian Heris J6 ; Danaii S7 ; Shahriar B1 ; Sadough M1 ; Chakarikhiavi F1 ; Teymouri Nobari S8 Show All Authors
Authors
  1. Badihi E1
  2. Sharifi P2
  3. Moradi A3
  4. Kamrani A1, 4
  5. Hassanzadeh A5
  6. Soltanizangbar MS1, 4
  7. Parsania S1
  8. Afandideh F1
  9. Ahmadian Heris J6
  10. Danaii S7
  11. Shahriar B1
  12. Sadough M1
  13. Chakarikhiavi F1
  14. Teymouri Nobari S8
  15. Aghebatimaleki L1
  16. Yousefi M1, 4
Show Affiliations
Authors Affiliations
  1. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iraq
  2. 2. Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iraq
  3. 3. Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iraq
  4. 4. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iraq
  5. 5. Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iraq
  6. 6. Department of Allergy and Clinical Immunology, Pediatric Hospital, Tabriz University of Medical Sciences, Tabriz, Iraq
  7. 7. Gynecology Department, Eastern Azerbaijan ACECR ART Center, Eastern Azerbaijan Branch of ACECR, Tabriz, Iraq
  8. 8. Department of Clinical Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iraq

Source: Human Immunology Published:2025


Abstract

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 β-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-β and decreasing IFN-γ 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. © 2025 American Society for Histocompatibility and Immunogenetics
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