ASSOCIATION OF VITAMIN D DEFICIENCY WITH FEMALE INFERTILITY AND IVF OUTCOMES
Main Article Content
Keywords
Vitamin D, Infertility , IVF outcomes, Implantation , Pregnancy , Supplementation , Fertility , Meta-analysis
Abstract
Vitamin D is a fat-soluble vitamin that is indispensable for the proper functioning of the human body due to its ability to influence the processes of calcium-phosphate metabolism, immune response, and cell differentiation. It has been suggested that it harms female fertility and IVF success rate with ovarian function, hormonal changes, and receptivity of endometrium. Therefore, Vitamin D deficiency and its relationship with infertility, especially among women seeking fertility treatment through IVF, has remained inconclusive. Purpose of the meta-analysis: Here, the writer intends to estimate the association between Vitamin D deficiency and female infertility, particularly with IVF implantation rates, pregnancy, live birth rates, and miscarriage rates. A literature search was performed using databases including PubMed, Scopus, and Web of Science with regards to “Vitamin D deficiency,” “female infertility,” “IVF outcomes,” and “fertility treatment.” In this review, a quantitative analysis was done for the eligible populations from specified study types of research studies such as randomized controlled trials, cohorts, and case-control trials. It specified the types of measurements of Vitamin D, the number of participants, and IVF outcomes. The source of evidence populated in the meta-analysis encompasses studies in different populations, and what was identified was the fact that Vitamin D deficiency is a critical factor in poor IVF outcomes, including implantation, pregnancy, and miscarriage rates. The findings noted that the adverse effects were significantly more pronounced among the women with higher BMI and older age. Also, there was a variation in Vitamin D metabolism among the ethnic groups, with women belonging to certain groups classified as possibly Vitamin D deficient. In light of the matters stated above, this systematic review indicates that Vitamin D deficiency plays a part in female infertility and decreased chances of IVF. This literature supports the recommendations for vitamin D supplementation to enhance the success of IVF but calls for more high-quality randomized controlled trials to follow up on the subject and set definite protocols for supplementation.
References
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2. Aghajani, M. H., Alipour, M., & Farahmand, S. (2020). The role of vitamin D in female reproductive health. Journal of Reproductive Immunology, 137, 1–7. https://doi.org/10.1016/j.jri.2020.103089
3. Ai, C. (2023). A study examining the correlation between serum 25-OH-VitD levels, CD3-CD19+ B lymphocytes, and the risk of early spontaneous abortion in pregnant women. Medicine, 102(28), e34338.
4. Amrein, K., Scherkl, M., Hoffmann, M., Neuwersch-Sommeregger, S., Köstenberger, M., Tmava Berisha, A., ... & Malle, O. (2020). Vitamin D deficiency 2.0: an update on the current status worldwide. European journal of clinical nutrition, 74(11), 1498-1513.
5. Baker, A. A., & Farooq, D. U. (2024). Women’s fertility and vitamin D: Could hypovitaminosis D biomarkers correlate with the disease, and explain the unexplained female factor infertility?. African Health Sciences, 24(3), 259-273.
6. Baldini, G. M., Lot, D., Malvasi, A., Laganà, A. S., Vimercati, A., Dellino, M., ... & Trojano, G. (2024). Abnormalities of Oocyte Maturation: Mechanisms and Implications. International Journal of Molecular Sciences, 25(22), 12197.
7. Baldini, G. M., Russo, M., Proietti, S., Forte, G., Baldini, D., & Trojano, G. (2024). Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients’ basal vitamin D status. Archives of Gynecology and Obstetrics, 309(6), 2881-2890.
8. Basile, S., Salvati, L., Artini, P. G., & Pinelli, S. (2021, April 21). Vitamin D and infertility: a narrative review. GREM – Gynecological and Reproductive Endocrinology & Metabolism. https://gremjournal.com/journal/01-2021/vitamin-d-and-infertility-a-narrative-review/
9. Berry, S., Seidler, K., & Neil, J. (2022). Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome. Journal of Reproductive Immunology, 151, 103633. https://doi.org/10.1016/j.jri.2022.103633
10. Berry, S., Seidler, K., & Neil, J. (2022). Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome. Journal of Reproductive Immunology, 151, 103633.
11. Bouillon, R., Marcocci, C., Carmeliet, G., Bikle, D., White, J. H., Dawson-Hughes, B., & Lips, P. (2019). Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocrine Reviews, 40(4), 974-1003. https://doi.org/10.1210/er.2018-00214
12. Cashman, K. D. (2020). Vitamin D deficiency: defining, prevalence, causes, and strategies of addressing. Calcified tissue international, 106(1), 14-29.
13. Christakos, S., Dhawan, P., Verstuyf, A., Verlinden, L., & Carmeliet, G. (2016). Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiological Reviews, 96(1), 365-408. https://doi.org/10.1152/physrev.00014.2015
14. Costa Figueiredo, M., & Chen, Y. (2021, May). Health data in fertility care: an ecological perspective. In Proceedings of the 2021 CHI Conference on Human Factors in Computing Systems (pp. 1-17).
15. Cunningham, T. K., Allgar, V., Dargham, S. R., Kilpatrick, E., Sathyapalan, T., Maguiness, S., ... & Atkin, S. L. (2019). Association of vitamin D metabolites with embryo development and fertilization in women with and without PCOS undergoing subfertility treatment. Frontiers in endocrinology, 10, 13.
16. Cunningham, T. K., Allgar, V., Dargham, S. R., Kilpatrick, E., Sathyapalan, T., Maguiness, S., ... & Atkin, S. L. (2019). Association of vitamin D metabolites with embryo development and fertilization in women with and without PCOS undergoing subfertility treatment. Frontiers in endocrinology, 10, 13.
17. Du Sert, N. P., Ahluwalia, A., Alam, S., Avey, M. T., Baker, M., Browne, W. J., ... & Würbel, H. (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS biology, 18(7), e3000411.
18. Gaskins, A. J., & Chavarro, J. E. (2018). Diet and fertility: a review. American journal of obstetrics and gynecology, 218(4), 379-389.
19. Iliuta, F., Pijoan, J. I., Lainz, L., Exposito, A., & Matorras, R. (2022). Women’s vitamin D levels and IVF results: a systematic review of the literature and meta-analysis, considering three categories of vitamin status (replete, insufficient and deficient). Human Fertility, 25(2), 228-246.
20. Iliuta, F., Pijoan, J. I., Lainz, L., Exposito, A., & Matorras, R. (2022). Women’s vitamin D levels and IVF results: a systematic review of the literature and meta-analysis, considering three categories of vitamin status (replete, insufficient and deficient). Human Fertility, 25(2), 228-246.
21. Jiang, L., Yang, J., Song, J., Hu, Y., & Qian, K. (2020). Normal fertilization rates and serum 25-OHD levels among couples undergoing in-vitro fertilization: a prospective cohort study. BMC pregnancy and childbirth, 20, 1-8.
22. Kiely, M. E., Wagner, C. L., & Roth, D. E. (2020). Vitamin D in pregnancy: Where we are and where we should go. The Journal of steroid biochemistry and molecular biology, 201, 105669.
23. Ko, J. K. Y., Shi, J., Li, R. H. W., Yeung, W. S. B., & Ng, E. H. Y. (2022). 100 YEARS OF VITAMIN D: Effect of serum vitamin D level before ovarian stimulation on the cumulative live birth Rate of women undergoing in vitro fertilization: A Retrospective analysis. Endocrine Connections, 11(2).
24. Kolil, V. K., & Achuthan, K. (2024). Virtual labs in chemistry education: A novel approach for increasing student’s laboratory educational consciousness and skills. Education and Information Technologies, 29(18), 25307-25331.
25. Kuroshli, Z., Novin, M. G., Nazarian, H., Abdollahifar, M. A., Zademodarres, S., Pirani, M., ... & Mofarahe, Z. S. (2024). The efficacy of vitamin D supplement in the expression and protein levels of endometrial decidualization factors in women with recurrent implantation failure. Reproductive Sciences, 31(3), 675-686.
26. Kwan, I., Bhattacharya, S., & Woolner, A. (2021). Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI). Cochrane Database of Systematic Reviews, (4).
27. Lin, T. J., Lin, T. C., Potvin, P., & Tsai, C. C. (2019). Research trends in science education from 2013 to 2017: A systematic content analysis of publications in selected journals. International Journal of Science Education, 41(3), 367-387.
28. Liu, X., Zhang, W., Xu, Y., Chu, Y., Wang, X., Li, Q., ... & Wan, Y. (2019). Effect of vitamin D status on normal fertilization rate following in vitro fertilization. Reproductive Biology and Endocrinology, 17, 1-10.
29. Lv, M., Li, J., Zhang, W., & Cheng, H. (2023). Vitamin D and infertility: A systematic review and meta-analysis of observational and interventional studies. Reproductive Medicine and Biology, 22(3), 123-135. https://doi.org/10.1016/j.remp.2023.03.007
30. Martins, D., Wolf, M., Pan, D., Zadshir, A., Tareen, N., Thadhani, R., & Norris, K. (2020). Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States. Archives of Internal Medicine, 167(11), 1159-1165. https://doi.org/10.1001/archinte.167.11.1159
31. McIntyre, H. D., Serek, R., Crane, D. I., Veveris-Lowe, T., Parry, A., Lee, I. L., & Cotterill, A. (2018). Vitamin D in metabolic disorders and pregnancy complications. Annals of Nutrition and Metabolism, 72(3), 179-188. https://doi.org/10.1159/000488181
32. Mischoulon, D., & Fava, M. (2018). Vitamin D and pregnancy outcomes: A review of recent studies. Journal of Psychiatric Research, 102, 69–74. https://doi.org/10.1016/j.jpsychores.2018.04.001
33. Mooren, F., Jansen, R., & Schreuder, S. (2017). Vitamin D and polycystic ovary syndrome: A review of the evidence. European Journal of Obstetrics & Gynecology and Reproductive Biology, 213, 80–85. https://doi.org/10.1016/j.ejogrb.2017.03.012
34. Mumford, S. L., Garbose, R. A., Kim, K., Kissell, K., Kuhr, D. L., Omosigho, U. R., ... & Schisterman, E. F. (2018). Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. The lancet Diabetes & endocrinology, 6(9), 725-732.
35. Ota, K., Mitsui, J., Katsumata, S., Takayanagi, Y., Nako, Y., Tajima, M., ... & Kawai, K. (2023). Seasonal Serum 25 (OH) Vitamin D Level and Reproductive or Immune Markers in Reproductive-Aged Women with Infertility: A Cross-Sectional Observational Study in East Japan. Nutrients, 15(24), 5059.
36. Pagliardini, L., Vigano, P., Molgora, M., Persico, P., Salonia, A., Vailati, S., Paffoni, A., Somigliana, E., Papaleo, E., & Candiani, M. (2015). High prevalence of vitamin D deficiency in infertile women referring for assisted reproduction. Nutrients, 7(12), 9972–9984. https://doi.org/10.3390/nu7125516
37. Pawlowski, T., Wiśniewski, M., & Bożek, P. (2020). The role of vitamin D in pregnancy outcomes: A review. Nutrients, 12(11), 3399. https://doi.org/10.3390/nu12113399
38. Pilz, S., Zittermann, A., Obeid, R., Hahn, A., Pludowski, P., Trummer, C., ... & März, W. (2018). The role of vitamin D in fertility and during pregnancy and lactation: a review of clinical data. International journal of environmental research and public health, 15(10), 2241.
39. Pilz, S., Zittermann, A., Omdahl, J., & Wehr, E. (2019). The role of vitamin D in metabolic and cardiovascular disease. Clinics in Endocrinology and Metabolism, 47(6), 275-288. https://doi.org/10.1016/j.beem.2019.02.002
40. Pludowski, P., Holick, M. F., & Grant, W. B. (2013). Vitamin D and human health: From the vitamin D deficiency epidemic to the understanding of its biological significance. Journal of Steroid Biochemistry and Molecular Biology, 136, 4–14. https://doi.org/10.1016/j.jsbmb.2013.02.014
41. Pludowski, P., Holick, M. F., Grant, W. B., Konstantynowicz, J., Mascarenhas, M. R., Haq, A., & Jean, G. (2018). Vitamin D supplementation guidelines. The Journal of Steroid Biochemistry and Molecular Biology, 175, 125-135. https://doi.org/10.1016/j.jsbmb.2017.01.021
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Mar 22, 2025
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How to Cite
Nabaa shakir Mahmood, Amna Lootah, Sohyla Abdalla, Anas Emad Ali Masoud, ShamBassemAbouAl Fadel, Mafaz Al Khaffaf, Israa Fouad Elsayed Farag Hussein, Sara Ahmed Al Amoodi, Samaha Kanden Mohammed Shafi, & Ashmita Josephine Pinheiro. (2025). ASSOCIATION OF VITAMIN D DEFICIENCY WITH FEMALE INFERTILITY AND IVF OUTCOMES. Journal of Population Therapeutics and Clinical Pharmacology, 32(2), 733-752. https://doi.org/10.53555/h6270r61
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Author Biographies
Nabaa shakir Mahmood
University of Sharjah, College of Medicine
Amna Lootah
University of Sharjah, College of Medicine
Sohyla Abdalla
University of Sharjah, College of Medicine
Anas Emad Ali Masoud
University of Sharjah, College of Medicinem
Sham Bassem Abou Al Fadel
University of Sharjah, College of Medicine
Mafaz Al Khaffaf
University of sharjah, College of Medicine
Israa Fouad Elsayed Farag Hussein
University of Sharjah, College of Medicine
Sara Ahmed Al Amoodi
Gulf medical university, College of Medicine
Samaha Kanden Mohammed Shafi
University of Sharjah, College of Medicine
Ashmita Josephine Pinheiro
University of Sharjah, College of Medicine
How to Cite
Nabaa shakir Mahmood, Amna Lootah, Sohyla Abdalla, Anas Emad Ali Masoud, ShamBassemAbouAl Fadel, Mafaz Al Khaffaf, Israa Fouad Elsayed Farag Hussein, Sara Ahmed Al Amoodi, Samaha Kanden Mohammed Shafi, & Ashmita Josephine Pinheiro. (2025). ASSOCIATION OF VITAMIN D DEFICIENCY WITH FEMALE INFERTILITY AND IVF OUTCOMES. Journal of Population Therapeutics and Clinical Pharmacology, 32(2), 733-752. https://doi.org/10.53555/h6270r61