The Role of Micronutrients on Fertility of Women with Polycystic Ovary Syndrome: A Systematic Review

Document Type : Review Article


1 PhD Student of Reproductive Health, Midwifery and Reproductive Health Research Center, Students Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Assistant Professor, Midwifery and Reproductive Health Research Center, Department of Midwifery and Reproductive Health, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.



Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and diet can affect it. Considering the high prevalence of polycystic ovary syndrome in women and its negative consequences on fertility, this review study was conducted with aim to investigate the role of micronutrients on the fertility of women with polycystic ovary syndrome.
Methods: In this systematic review study, to find the related articles, international databases (ScienceDirect, Embase, Scopus, PubMed) and Persian language databases (Magiran, SID and IranMedex) were searched with different combinations of keywords related to "polycystic ovary syndrome" and " "micronutrients" and "fertility" without time limit until February 2023 using the Verhagen scale.
Results: Out of 1080 reviewed articles, finally 13 articles were included in the study. Five studies investigated the indirect mechanisms of micronutrients on factors affecting fertility; in two studies, no statistically significant difference was observed, and in three studies, beneficial effects on insulin metabolism and lipid parameters, regulation of menstruation, regulation of LH/FSH ratio were reported. Of the eight studies that investigated ovarian function, seven studies found improved ovarian function. Most of the studies showed the positive effects of micronutrients on the fertility of women with polycystic ovary syndrome.
Conclusion: Micronutrients seem to be associated with improved fertility in women with polycystic ovary syndrome.


Main Subjects

  1. Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C, et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecological Endocrinology 2007; 23(12):700-3.
  2. Barnard L, Ferriday D, Guenther N, Strauss B, Balen AH, Dye L. Quality of life and psychological well being in polycystic ovary syndrome. Human reproduction 2007; 22(8):2279-86.
  3. Jalilian A, Kiani F, Sayehmiri F, Sayehmiri K, Khodaee Z, Akbari M. Prevalence of polycystic ovary syndrome and its associated complications in Iranian women: A meta-analysis. Iranian journal of reproductive medicine 2015; 13(10):591.
  4. Mirghafourvand M, Mohammad-Alizadeh Charandabi S, Aliasghari F. Assessment of health promoting lifestyle status and its socio-demographic predictors in women with polycystic ovarian syndrome. Hayat 2017; 22(4):394-407.
  5. Akhtari E, Mokaberinejad R, Tajadini H. Treatment of Menstrual Disorder, Depression and Sexual Dysfunction in A 27-Year-Old Woman With Polycystic Ovary Syndrome Based on Iranian Traditional Medicine (Case Report). Asian J Clin Case Rep Trad Alt Med 2017; 1(1):43-50.
  6. Hemmatipour A, Shafiee SM, Baraz S, Edivandi S, Mosavi SA. Pregnancy outcomes in mothers with gestational diabetes mellitus with and without polycystic ovary syndrome. Journal of Isfahan Medical School 2018; 36(497):1142-8.
  7. Shoham Z, Weissman A. Polycystic ovarian disease: obesity and insulin resistance 1998: 263-72.
  8. Edwards RG, Beard HK. Is the success of human IVF more a matter of genetics and evolution than growing blastocysts?. Human Reproduction 1999; 14(1):1-6.
  9. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertility and sterility 2005; 83(5):1454-60.
  10. Howles CM, Macnamee MC, Edwards RG, Goswamy R, Steptoe PC. Effect of high tonic levels of luteinising hormone on outcome of in-vitro fertilisation. The Lancet. 1986 Aug 30; 328(8505):521-2.
  11. Franks S, Roberts R, Hardy K. Gonadotrophin regimens and oocyte quality in women with polycystic ovaries. Reproductive BioMedicine Online 2003; 6(2):181-4.
  12. Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nature reviews Disease primers 2016; 2(1):1-18.
  13. Engmann L, Maconochie N, Sladkevicius P, Bekir J, Campbell S, Tan SL. The outcome of in-vitro fertilization treatment in women with sonographic evidence of polycystic ovarian morphology. Human Reproduction 1999; 14(1):167-71.
  14. Järvelä IY, Sladkevicius P, Kelly S, Ojha K, Campbell S, Nargund G. Quantification of ovarian power Doppler signal with three-dimensional ultrasonography to predict response during in vitro fertilization. Obstetrics & Gynecology 2003; 102(4):816-22.
  15. Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. Journal of women's health 2015; 24(4):299-307.
  16. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine 2010; 8(1):1-10.
  17. Burkman RT. Berek & Novak’s gynecology. Jama 2012; 308(5):516-7.
  18. Sourinejad H, Savabi Esfahani M, Tarrahi MJ, Adib Moghaddam E. Outcomes and Challenges associated with In vitro Fertilization in Women with Polycystic Ovary Syndrome: A review study. Journal of Sabzevar University of Medical Sciences 2021; 28(3):359-71.
  19. Kyrou I, Weickert MO, Randeva HS. Diagnosis and management of polycystic ovary syndrome (PCOS). Endocrinology and diabetes: Case studies, questions and commentaries 2015: 99-113.
  20. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human reproduction 2018; 33(9):1602-18.
  21. Gibson-Helm M, Dokras A, Karro H, Piltonen T, Teede HJ. Knowledge and practices regarding polycystic ovary syndrome among physicians in Europe, North America, and internationally: an online questionnaire-based study. InSeminars in Reproductive Medicine 2018; 36(01):19-27.
  22. Teede HJ, Misso ML, Deeks AA, Moran LJ, Stuckey BG, Wong JL, et al. Assessment and management of polycystic ovary syndrome: summary of an evidence-based guideline. The Medical Journal of Australia 2011; 195(6):S65.
  23. Asemi Z, Esmaillzadeh A. DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial. Hormone and metabolic research 2014; 47(03):232-8.
  24. Alamolhoda H, Simbar M, Asghari G, Mirmiran P, Azizi F. Trans fatty acids and gestational diabetes mellitus: systematic review. Iranian Journal of Endocrinology and Metabolism 2016; 18(1):63-72.
  25. Ramakrishnan U, Grant F, Goldenberg T, Zongrone A, Martorell R. Effect of women's nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review. Paediatric and perinatal epidemiology 2012; 26:285-301.
  26. Schaefer E, Nock D. The impact of preconceptional multiple-micronutrient supplementation on female fertility. Clinical Medicine Insights: Women's Health 2019; 12:1179562X19843868.
  27. Banaei M, Alamolhoda SH, Beheshti Nasab M, Mohamadkhani Shahri L, Bayat F. Relationship between level of vitamins and hydatiform mole in women: a systematic review study. The Iranian Journal of Obstetrics, Gynecology and Infertility 2020; 23(5):95-104.
  28. Paknahad Z, Tarrahi MJ, Shaghaghi F, Safinejad H, Asadi L, Mohebbi-Dehnavi Z. The role of micronutrients in male and female fertility: A review study. The Iranian Journal of Obstetrics, Gynecology and Infertility 2021; 24(1):87-98.
  29. Verhagen AP, De Vet HC, De Bie RA, Kessels AG, Boers M, Bouter LM, et al. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. Journal of clinical epidemiology 1998; 51(12):1235-41.
  30. Asadi M, Matin N, Frootan M, Mohamadpour J, Qorbani M, Tanha FD. Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial. Archives of gynecology and obstetrics 2014; 289:865-70.
  31. Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F. Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial. European Review for Medical & Pharmacological Sciences 2011; 15(5):509-14.
  32. dehghani Firouzabadi R, Aflatoonian A, Modarresi S, Sekhavat L, MohammadTaheri S. Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complementary therapies in clinical practice 2012; 18(2):85-8.
  33. Chen J, Guo Q, Pei YH, Ren QL, Chi L, Hu RK, et al. Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study. BMC women's health 2020; 20:1-9.
  34. Dastorani M, Aghadavod E, Mirhosseini N, Foroozanfard F, Zadeh Modarres S, Amiri Siavashani M, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reproductive Biology and Endocrinology 2018; 16:1-7.
  35. Lerchbaum E, Theiler-Schwetz V, Kollmann M, Wölfler M, Pilz S, Obermayer-Pietsch B, et al. Effects of vitamin D supplementation on surrogate markers of fertility in pcos women: A randomized controlled trial. Nutrients 2021; 13(2):547.
  36. Pal L, Zhang H, Williams J, Santoro NF, Diamond MP, Schlaff WD, et al. Vitamin D status relates to reproductive outcome in women with polycystic ovary syndrome: secondary analysis of a multicenter randomized controlled trial. The Journal of Clinical Endocrinology & Metabolism 2016; 101(8):3027-35.
  37. Fatemi F, Mohammadzadeh A, Sadeghi MR, Akhondi MM, Mohammadmoradi S, Kamali K, et al. Role of vitamin E and D3 supplementation in Intra-Cytoplasmic Sperm Injection outcomes of women with polycystic ovarian syndrome: A double blinded randomized placebo-controlled trial. Clinical nutrition ESPEN 2017; 18:23-30.
  38. Mendoza N, Galan MI, Molina C, Mendoza-Tesarik R, Conde C, Mazheika M, et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecological Endocrinology 2020; 36(5):398-401.
  39. Colazingari S, Treglia M, Najjar R, Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. Archives of Gynecology and Obstetrics 2013; 288:1405-11.
  40. Rasheedy R, Sammour H, Elkholy A, Salim Y. The efficacy of vitamin D combined with clomiphene citrate in ovulation induction in overweight women with polycystic ovary syndrome: a double blind, randomized clinical trial. Endocrine 2020; 69:393-401.
  41. Morsy AA, Sabri NA, Mourad AM, Mojahed EM, Shawki MA. Randomized controlled open‐label study of the effect of vitamin E supplementation on fertility in clomiphene citrate‐resistant polycystic ovary syndrome. Journal of Obstetrics and Gynaecology Research 2020; 46(11):2375-82.
  42. Tomlinson MJ, Amissah-Arthur JB, Thompson KA, Kasraie JL, Bentick B. Infertility: prognostic indicators for intrauterine insemination (IUI): statistical model for IUI success. Human Reproduction 1996; 11(9):1892-6.
  43. Kovacs P, Matyas SZ, Boda K, Kaali SG. The effect of endometrial thickness on IVF/ICSI outcome. Human Reproduction 2003; 18(11):2337-41.
  44. Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertility and sterility 2010; 94(4):1314-9.
  45. Barrera D, Avila E, Hernández G, Halhali A, Biruete B, Larrea F, et al. Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. The Journal of steroid biochemistry and molecular biology 2007; 103(3-5):529-32.
  46. Stephanou A, Ross R, Handwerger S. Regulation of human placental lactogen expression by 1, 25-dihydroxyvitamin D3. Endocrinology 1994; 135(6):2651-6.
  47. Momeni M, Rahbar MH, Kovanci E. A meta-analysis of the relationship between endometrial thickness and outcome of in vitro fertilization cycles. Journal of human reproductive sciences 2011; 4(3):130.
  48. Turer CB, Lin H, Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics 2013; 131(1):e152-61.
  49. Zadeh-Vakili A, Tehrani FR, Daneshpour MS, Zarkesh M, Saadat N, Azizi F. Genetic polymorphism of vitamin D receptor gene affects the phenotype of PCOS. Gene 2013; 515(1):193-6.
  50. Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. British journal of clinical pharmacology 2018; 84(6):1121-7.
  51. Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertility and sterility 2014; 102(2):460-8.
  52. Johansson J, Stener-Victorin E. Polycystic ovary syndrome: effect and mechanisms of acupuncture for ovulation induction. Evidence-Based Complementary and Alternative Medicine 2013; 2013.
  53. Moridi I, Chen A, Tal O, Tal R. The association between vitamin D and anti-Müllerian hormone: a systematic review and meta-analysis. Nutrients 2020; 12(6):1567.
  54. Vause TD, Cheung AP, Sierra S, Claman P, Graham J, Guillemin JA, et al. Ovulation induction in polycystic ovary syndrome. Journal of Obstetrics and Gynaecology Canada 2010; 32(5):495-502.
  55. Polyzos NP, Anckaert E, Guzman L, Schiettecatte J, Van Landuyt L, Camus M, et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Human reproduction 2014; 29(9):2032-40.
  56. Garbedian K, Boggild M, Moody J, Liu KE. Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. Canadian Medical Association Open Access Journal 2013; 1(2):E77-82.
  57. Rudick BJ, Ingles SA, Chung K, Stanczyk FZ, Paulson RJ, Bendikson KA. Influence of vitamin D levels on in vitro fertilization outcomes in donor-recipient cycles. Fertility and sterility 2014; 101(2):447-52.
  58. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science 1922; 56(1458):650-1.
  59. Tarín JJ, Pérez‐Albalá S, Cano A. Oral antioxidants counteract the negative effects of female aging on oocyte quantity and quality in the mouse. Molecular reproduction and development 2002; 61(3):385-97.
  60. Alizadeh L, Alamolhoda SH. The role of antioxidants and the risk of human papillomavirus infection and cervical intraepithelial neoplasia: A systematic review. Iranian Journal of Obstetrics, Gynecology and Infertility 2023; 26(1):84-93.
  61. Majid RB, Rezazadeh H, Asvadi-Kermani I, Ghazi-Khansari M, Golchin M, Sarmad M. Effect of vitamin e on uroepithelial cells and changes of urinary sediments in oncology hospital nursing personnel. Journal of clinical and diagnostic research: JCDR 2013;7(11):2570.
  62. Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ. Antioxidants for female subfertility. Cochrane Database of Systematic Reviews 2020(8).
  63. Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S. Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. European Review for Medical & Pharmacological Sciences 2011; 15(4):452-7.
  64. Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Human Reproduction 2002; 17(6):1591-6.
  65. Larner J. Multiple pathways in insulin signaling-fitting the covalent and allosteric puzzle pieces together. Endocrine 1994; 2(3):167-71.