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Ameliorating Effects of Natural Antioxidant Compounds on Female Infertility: a Review

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Abstract

The prevalence of female infertility cases has been increasing at a frightening rate, affecting approximately 48 million women across the world. However, oxidative stress has been recognized as one of the main mediators of female infertility by causing various reproductive pathologies in females such as endometriosis, PCOS, preeclampsia, spontaneous abortion, and unexplained infertility. Nowadays, concerned women prefer dietary supplements with antioxidant properties over synthetic drugs as a natural way to lessen the oxidative stress and enhance their fertility. Therefore, the current review is an attempt to explore the efficacy of various natural antioxidant compounds including vitamins, carotenoids, and plant polyphenols and also of some medicinal plants in improving the fertility status of females. Our summarization of recent findings in the current article would pave the way toward the development of new possible antioxidant therapy to treat infertility in females. Natural antioxidant compounds found in fruits, vegetables, and other dietary sources, alone or in combination with other antioxidants, were found to be effective in ameliorating the oxidative stress-mediated infertility problems in both natural and assisted reproductive settings. Numerous medicinal plants showed promising results in averting the various reproductive disorders associated with female infertility, suggesting a plant-based herbal medicine to treat infertility. Although optimum levels of natural antioxidants have shown favorable results, however, their excessive intake may have adverse health impacts. Therefore, larger well-designed, dose–response studies in humans are further warranted to incorporate natural antioxidant compounds into the clinical management of female infertility.

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References

  1. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22:150612.

    Google Scholar 

  2. Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21:411–26.

    PubMed  Google Scholar 

  3. Slama R, Hansen OK, Ducot B, Bohet BA, Sorensen D, Allemand LG, et al. Estimation of the frequency of involuntary infertility on a nation-wide basis. Hum Reprod. 2012;27:1489–98.

    CAS  PubMed  Google Scholar 

  4. Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, et al. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99:1324–31.

    PubMed  PubMed Central  Google Scholar 

  5. Yu SL, Yap C. Investigating the infertile couple. Ann Acad Med Singap. 2003;32:611–3 quiz 614.

    CAS  PubMed  Google Scholar 

  6. Sengupta P, Dutta S, Tusimin MB, Irez T, Kulak EK. Sperm counts in Asian men: reviewing the trend of past 50 years. Asian Pac J Reprod. 2018;7(2):87–92.

    Google Scholar 

  7. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9:e1001356.

    PubMed  PubMed Central  Google Scholar 

  8. DeCherney A, Nathan L, Eskandari M, Cadieux M. Current obstetric & gynecologic diagnosis & treatment. McGraw Hill. N Y. 2003;6:979–90.

    Google Scholar 

  9. Duckitt K. Infertility and subfertility. Clin Evid. 2003:2044–73.

  10. Evers JL. Female subfertility. Lancet. 2002;360:151–9.

    PubMed  Google Scholar 

  11. Pinnelli A, Di-Cesare M. Human fertility: sociodemographic aspects. Contraception. 2005;72:30–7.

    Google Scholar 

  12. Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility - a clinician’s perspective. Reprod BioMed Online. 2005;11:641–50.

    CAS  PubMed  Google Scholar 

  13. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49.

    PubMed  PubMed Central  Google Scholar 

  14. Gupta S, Ghulmiyyah J, Sharma R, Halabi J, Agarwal A. Power of proteomics in linking oxidative stress and female infertility. Biomed Res Int. 2014;9162127.

  15. Sekhon LH, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Current Women’s Health Reviews. 2010;6:84–95.

    CAS  Google Scholar 

  16. Agarwal A, Tadros H, Tvrda E. Role of oxidants and antioxidants in female reproduction. In: Armstrong D, Stratton RD, editors. Oxidative stress and antioxidant protection: the science of free radical biology and disease. Hoboken: Wiley; 2016. p. 253–80.

    Google Scholar 

  17. Agarwal A, Sengupta P. Oxidative stress and its association with male infertility. In: Parekattil SJ, Esteves SC, Agarwal A, editors. Male infertility. 2nd ed). Gewerbestrasse 11, 6330 Cham, Switzerland; 2020. p. 57–68.

    Google Scholar 

  18. Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008;14(3):243–58.

    CAS  PubMed  Google Scholar 

  19. Agarwal A. Role of oxidative stress in endometriosis. Reprod BioMed Online. 2006;13:126–34.

    PubMed  Google Scholar 

  20. Agarwal A, Allamaneni SS. Role of free radicals in female reproductive diseases and assisted reproduction. Reprod BioMed Online. 2004;9:338–47.

    CAS  PubMed  Google Scholar 

  21. Gupta S, Agarwal A, Banerjee J, Alvarez JG. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet Gynecol Surv. 2007;62:335–47.

    PubMed  Google Scholar 

  22. Agarwal A, Gupta S, Sekhon L, Shah R. Redox considerations in female reproductive function and assisted reproduction: from molecular mechanisms to health implications. Antioxid Redox Signal. 2008;10:1375–403.

    CAS  PubMed  Google Scholar 

  23. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.

    CAS  PubMed  Google Scholar 

  24. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2018;16(1):80.

    PubMed  PubMed Central  Google Scholar 

  25. Bouayed J, Bohn T. Exogenous antioxidants—double-edged swords in cellular redox state. Oxidative Med Cell Longev. 2010;3:228–37.

    Google Scholar 

  26. Huang HY, Appel LJ, Croft KD, Miller ER, Mori TA, Puddey IB. Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr. 2002;76:549–55.

    CAS  PubMed  Google Scholar 

  27. Upritchard JE, Schuurman CR, Wiersma A, Tijburg LB, Coolen SA, Rijken PJ, et al. Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults. Am J Clin Nutr. 2003;78:985–92.

    CAS  PubMed  Google Scholar 

  28. Dragsted LO, Pedersen A, Hermetter A, Basu S, Hansen M, Haren GR, et al. The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidant defense in healthy nonsmokers. Am J Clin Nutr. 2004;79:1060–72.

    CAS  PubMed  Google Scholar 

  29. Pajk T, Rezar V, Levart A, Salobir J. Efficiency of apples, strawberries, and tomatoes for reduction of oxidative stress in pigs as a model for humans. Nutrition. 2006;22:376–84.

    CAS  PubMed  Google Scholar 

  30. Parazzini F, Chiaffarino F, Surace M, Chatenoud L, Cipriani S, Chiantera V, et al. Selected food intake and risk of endometriosis. Hum Reprod. 2004;19:1755–9.

    CAS  PubMed  Google Scholar 

  31. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Use of multivitamins, intake of B vitamins and risk of ovulatory infertility. Fertil Steril. 2008;89:668–76.

    CAS  PubMed  Google Scholar 

  32. Prior RL, Gu L, Wu X, Jacob RA, Sotoudeh G, Kader AA, et al. Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status. J Am Coll Nutr. 2007;26:170–81.

    CAS  PubMed  Google Scholar 

  33. Chen B, Tuuli MG, Longtine MS, Shin JS, Lawrence R, Inder T, et al. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and human placental trophoblasts. Am J Physiol Endocrinol Metab. 2012;302:E1142–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Gadhok AK, Sharma TK, Sinha M, Khunteta R, Vardey SK, Sahni P, et al. Natural antioxidant vitamins status in pregnancies complicated with intrauterine growth restriction. Clin Lab. 2017;63:941–5.

    CAS  PubMed  Google Scholar 

  35. Gaskins AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol. 2018;218:379–89.

    PubMed  Google Scholar 

  36. Silvestris E, Lovero D, Palmirotta R. Nutrition and female fertility: an interdependent correlation. Front Endocrinol. 2019;10:346.

    Google Scholar 

  37. Jaradat N, Zaid AN. Herbal remedies used for the treatment of infertility in males and females by traditional healers in the rural areas of the West Bank/Palestine. BMC Complement Altern Med. 2019;19:194.

    PubMed  PubMed Central  Google Scholar 

  38. Fang RC, Tsaim YT, Laim JN, Yehm CH, Wum CT. The traditional Chinese medicine rescription pattern of endometriosis patients in Taiwan: a population-based study. Evid Based Complement Alternat Med. 2012;591391.

  39. Kort DH, Lobo RA. Preliminary evidence that cinnamon improves menstrual cyclicity in women with polycystic ovary syndrome: a randomized controlled trial. Am J Obstet Gynecol. 2014;211:487.e1–6.

    CAS  Google Scholar 

  40. Khaki A, Khaki AA, Ezzatzadeh A, Hamidreza A. Effect of Ocimum basilicum on ovary tissue histopathology after exposure to electromagnetic fields (EMF) in rats. Afr J Pharm Pharmacol. 2013;7:1703–6.

    Google Scholar 

  41. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle factors and reproductive health: taking control of your fertility. Reprod Biol Endocrinol. 2013;11:66.

    PubMed  PubMed Central  Google Scholar 

  42. Bhardwaj JK, Saraf P. Influence of toxic chemicals on female reproduction: a review. Cell Biol Res Ther. 2014a;3:1.

    Google Scholar 

  43. Bhardwaj JK, Saraf P. N-acetyl-l-cysteine mediated regulation of DNA fragmentation, an apoptotic event, against methoxychlor toxicity in the granulosa cells of ovarian antral follicles. Mutat Res Gen Tox En. 2020;858–860:503222.

  44. Howe G, Westhoff C, Vessey M, Yeates D. Effects of age, cigarette smoking, and other factors on fertility: findings in a large prospective study. Br Med J (Clin Res Ed). 1985;290:1697–700.

    CAS  Google Scholar 

  45. Hakim RB, Gray RH, Zacur H. Alcohol and caffeine consumption and decreased fertility. Fertil Steril. 1998;70:632–7.

    CAS  PubMed  Google Scholar 

  46. Huang J, Okuka M, McLean M, Keefe DL, Liu L. Effects of cigarette smoke on fertilization and embryo development in vivo. Fertil Steril. 2009;92:1456–65.

    CAS  PubMed  Google Scholar 

  47. Kovacic P. Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: electron transfer and reactive oxygen species. Med Hypotheses. 2005;65:90–6.

    CAS  PubMed  Google Scholar 

  48. Ornoy A. Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis on diabetic embryopathy. Reprod Toxicol. 2007;24:31–41.

    CAS  PubMed  Google Scholar 

  49. Uzumcu M, Zachow R. Developmental exposure to environmental endocrine disruptors: consequences within the ovary and on female reproductive function. Reprod Toxicol. 2007;23:337–52.

    CAS  PubMed  Google Scholar 

  50. Bhardwaj JK, Saraf P. Malathion-induced granulosa cell apoptosis in caprine antral follicles: an ultrastructural and flow cytometric analysis. Microsc Microanal. 2014b;20:1861–8.

    CAS  PubMed  Google Scholar 

  51. Bhardwaj JK, Mittal M, Saraf P, Kumari P. Pesticides induced oxidative stress and female infertility: a review. Toxin Rev. 2018a;39:1–13.

    Google Scholar 

  52. Bhardwaj JK, Saraf P. N-acetyl cysteine-mediated effective attenuation of methoxychlor-induced granulosa cell apoptosis by counteracting reactive oxygen species generation in caprine ovary. Environ Toxicol. 2015;32:156–66.

    PubMed  Google Scholar 

  53. Bhardwaj JK, Saraf P. granulosa cell apoptosis by impairing antioxidant defense system and cellular integrity in caprine antral follicles post malathion exposure. Environ Toxicol. 2015;31(12):1944–54.

    PubMed  Google Scholar 

  54. Faroon OM, Keith S, Jones D, de Rosa C. Effects of polychlorinated biphenyls on development and reproduction. Toxicol Ind Health. 2001;17(3):63–93.

    CAS  PubMed  Google Scholar 

  55. Lei HL, Wei HJ, Ho HY, Liao KW, Chien LC. Relationship between risk factors for infertility in women and lead, cadmium, and arsenic blood levels: a cross-sectional study from Taiwan. BMC Public Health. 2015;15:1220.

    PubMed  PubMed Central  Google Scholar 

  56. Guerra-Tamayo JL, Hernandez-Cadena L, Tellez-Rojo MM, Mercado-Garcia Adel S, Solano-Gonzalez M, Hernandez-Avila M, et al. Time to pregnancy and lead exposure. Salud Publica Mex. 2003;45(Suppl. 2):S189–95.

    PubMed  Google Scholar 

  57. Lee S, Min J, Min K. Female infertility associated with blood lead and cadmium levels. Int J Environ Res Public Health. 2020;17(5):1794.

    CAS  PubMed Central  Google Scholar 

  58. Sloboda DM, Howie GJ, Pleasants A, Gluckman PD, Vickers MH. Pre and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. PLoS One. 2009;4:e6744.

    PubMed  PubMed Central  Google Scholar 

  59. da Silva FT, de Bittencourt BF, Sampaio FJ, da Fonte Ramos C. Maternal malnutrition during lactation affects folliculogenesis, gonadotropins, and leptin receptors in adult rats. Nutrition. 2010;26:1000–7.

    Google Scholar 

  60. Gluckman PD, Hanson MA, Cooper C, Kent L. Effect of in utero and early life conditions on adult health and disease. N Engl J Med. 2008;359:61–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Bernal AB, Vickers MH, Hampton MB, Poynton RA, Sloboda DM. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One. 2010;5:e15558.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Saben J, Lindsey F, Zhong Y, Thakali K, Badger TM, Andres A, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta. 2014;35:171–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Malti N, Merzouk H, Merzouk SA, Loukidi B, Karaouzene N, Malti A, et al. Oxidative stress and maternal obesity: feto-placental unit interaction. Placenta. 2014;35:411–6.

    CAS  PubMed  Google Scholar 

  64. Zhang X, Strakovsky R, Zhou D, Zhang Y, Pan YX. A maternal high-fat diet represses the expression of antioxidant defense genes and induces the cellular senescence pathway in the liver of male offspring rats. J Nutr. 2011;141:1254–9.

    CAS  PubMed  Google Scholar 

  65. Perrone S, Tataranno ML, Santacroce A, Bracciali C, Riccitelli M, Alagna MG, et al. Fetal programming, maternal nutrition, and oxidative stress hypothesis. J Pediatr Biochem. 2016;6:96–102.

    Google Scholar 

  66. Adeoye O, Olawumi J, Opeyemi A, Christiania O. Review on the role of glutathione on oxidative stress and infertility. JBRA Assist Reprod. 2018;22:61–6.

    PubMed  PubMed Central  Google Scholar 

  67. Dutta S, Majzoub A, Agarwal A. Oxidative stress and sperm function: a systematic review on evaluation and management. Arab J Urol. 2019;17(2):87–97.

    PubMed  PubMed Central  Google Scholar 

  68. Agarwal A, Sharma RK, Nallella KP, Thomas AJ Jr, Alvarez JG, Sikka SC. Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril. 2006;86(4):878–85.

    CAS  PubMed  Google Scholar 

  69. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008;59:2–11.

    CAS  PubMed  Google Scholar 

  70. Doshi SD, Sharma RK, Agarwal A. Oxidative stress in unexplained male infertility. In: Schattman GL, Esteves SC, Agarwal A, editors. Unexplained infertility: pathophysiology, evaluation and treatment. New York City: Springer; 2015. p. 81–9.

    Google Scholar 

  71. Agarwal A, Hamada A, Esteves SC. Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat Rev Urol. 2012;9:678–90.

    PubMed  Google Scholar 

  72. Hamada A, Esteves SC, Agarwal A. Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol. 2013;10:26–37.

    CAS  PubMed  Google Scholar 

  73. Potts JM, Pasqualotto FF. Seminal oxidative stress in patients with chronic prostatitis. Andrologia. 2003;35:304–8.

    CAS  PubMed  Google Scholar 

  74. Sabeti P, Pourmasumi S, Rahiminia T, Akyash F, Talebi AR. Etiologies of sperm oxidative stress. Int J Reprod Biomed (Yazd). 2016;14:231–40.

    CAS  Google Scholar 

  75. Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol. 2009;21:219–22.

    PubMed  PubMed Central  Google Scholar 

  76. Dennery PA. Role of redox in fetal development and neonatal diseases. Antioxid Redox Signal. 2004;6:147–53.

    CAS  PubMed  Google Scholar 

  77. Sharma RK, Agarwal A. Role of reactive oxygen species in gynecologic diseases. Reprod Med Bio. 2004;3:177–99.

    CAS  Google Scholar 

  78. Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28.

    PubMed  PubMed Central  Google Scholar 

  79. Rizzo A, Roscino MT, Binetti F, Sciorsci RL. Roles of reactive oxygen species in female reproduction. Reprod Domest Anim. 2012;47:344–52.

    CAS  PubMed  Google Scholar 

  80. Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxidative Med Cell Longev. 2017;4371714. https://doi.org/10.1155/2017/4371714.

  81. de Bruin JP, Dorland M, Spek ER, Posthuma G, van Haaften M, Looman CW, et al. Ultrastructure of the resting ovarian follicle pool in healthy young women. Biol Reprod. 2002;66:1151–60.

    PubMed  Google Scholar 

  82. Lim J, Luderer U. Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary. Biol Reprod. 2011;84:775–82.

    CAS  PubMed  Google Scholar 

  83. Myatt L, Cui X. Oxidative stress in the placenta. Histochem Cell Biol. 2004;122:369–82.

    CAS  PubMed  Google Scholar 

  84. Fainaru O, Almog B, Pinchuk I, Kupferminc MJ, Lichtenberg D, Many A. Active labour is associated with increased oxidisibility of serum lipids ex vivo. BJOG. 2002;109:938–41.

    CAS  PubMed  Google Scholar 

  85. Mocatta TJ, Winterbourn CC, Inder TE, Darlow BA. The effect of gestational age and labour on markers of lipid and protein oxidation in cord plasma. Free Radic Res. 2004;38:185–91.

    CAS  PubMed  Google Scholar 

  86. Wall PD, Pressman EK, Woods JRJ. Preterm premature rupture of the membranes and antioxidants: the free radical connection. J Perinat Med. 2002;30:447–57.

    CAS  PubMed  Google Scholar 

  87. Pressman EK, Cavanaugh JL, Mingione M, Norkus EP, Woods JR. Effects of maternal antioxidant supplementation on maternal and fetal antioxidant levels: a randomized, double-blind study. Am J Obstet Gynecol. 2003;189:1720–5.

    CAS  PubMed  Google Scholar 

  88. Agarwal A, Said TM, Bedaiwy MA, Banerjee J, Alvarez JG. Oxidative stress in an assisted reproductive techniques setting. Fertil Steril. 2006;86:503–12.

    CAS  PubMed  Google Scholar 

  89. Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell B. 2010;42:1634–50.

    CAS  Google Scholar 

  90. Takagi Y, Nikaido T, Toki T, Kita N, Kanai M, Ashida T, et al. Levels of oxidative stress and redox-related molecules in the placenta in preeclampsia and fetal growth restriction. Virchows Arch. 2004;444:49–55.

    CAS  PubMed  Google Scholar 

  91. Harma M, Kocyigit A. Comparison of protein carbonyl and total plasma thiol concentrations in patients with complete hydatidiform mole with those in healthy pregnant women. Acta Obstet Gynecol Scand. 2004;83:857–60.

    PubMed  Google Scholar 

  92. Harma M, Erel O. Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly. 2003;133:563–6.

    CAS  PubMed  Google Scholar 

  93. Loeken MR. Free radicals and birth defects. J Matern Fetal Neonatal Med. 2004;15:6–14.

    CAS  PubMed  Google Scholar 

  94. Lagod L, Paszkowski T, Sikorski R, Rola R. The antioxidant/prooxidant balance in pregnancy complicated by spontaneous abortion. Ginekol Pol. 2001;72:1073–8.

    CAS  PubMed  Google Scholar 

  95. Polak G, Koziol-Montewka M, Gogacz M, Blaszkowska I, Kotarski J. Total antioxidant status of peritoneal fluid in infertile women. Eur J Obstet Gynecol Reprod Biol. 2001;94:261–3.

    CAS  PubMed  Google Scholar 

  96. Dubinskaia ED, Gasparov AS, Fedorova TA, Lapteva NV. Role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility (review). Vestn Ross Akad Med Nauk. 2013;8:14–9.

    Google Scholar 

  97. Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxidative Med Cell Longev. 2016;2016:8589318.

    Google Scholar 

  98. Iborra A, Palacio JR, Martinez P. Oxidative stress and autoimmune response in the infertile woman. Chem Immunol Allergy. 2005;88:150–62.

    CAS  PubMed  Google Scholar 

  99. Smits RM, Mackenzie-Proctor R, Fleischer K, Showell MG. Antioxidants in fertility: impact on male and female reproductive outcomes. Fertil Steril. 2018;110:4.

    Google Scholar 

  100. Lobo V, Patil A, Phatak A, Chandra VN. Free radicals, antioxidants and functional foods: impact on human health. Phcog Rev. 2010;4:118–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Go YM, Jones DP. Redox compartmentalization in eukaryotic cells. Biochim Biophys Acta. 2008;1780:1273–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol. 2001;54:176–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Pham-Huy LA, He H, Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci. 2008;4:89–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Luberda Z. The role of glutathione in mammalian gametes. Reprod Biol. 2005;5:5–17.

    PubMed  Google Scholar 

  105. Hyman M. Glutathione: the mother of all antioxidants. The Blog. 2011. Available at: https://www.huffingtonpost.com/ dr-mark-hyman/glutathione-the-mother-of_b_530494.html. .

  106. Mukherjee A, Malik H, Saha AP, Dubey A, Singhal DK, Boateng S, et al. Resveratrol treatment during goat oocytes maturation enhances developmental competence of parthenogenetic and hand-made cloned blastocysts by modulating intracellular glutathione level and embryonic gene expression. J Assist Reprod Genet. 2014;31:229–39.

    PubMed  Google Scholar 

  107. Orsi NM, Gopichandran N, Leese HJ, Picton HM, Harris SE. Fluctuations in bovine ovarian follicular fluid composition throughout the oestrous cycle. Reproduction. 2005;129:219–28.

    CAS  PubMed  Google Scholar 

  108. Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D, Dekel N. Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci U S A. 2011;108:1462–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Board PG, Menon D. Glutathione transferases, regulators of cellular metabolism and physiology. Biochim Biophys Acta. 1830;2013:3267–388.

    Google Scholar 

  110. Combelles CM, Holick EA, Paolella LJ, Walker DC, Wu Q. Profiling of superoxide dismutase isoenzymes in compartments of the developing bovine antral follicles. Reproduction. 2010;139:871–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. El-Shahat KH, Kandil M. Antioxidant capacity of follicular fluid in relation to follicular size and stage of estrous cycle in buffaloes. Theriogenology. 2012;77:1513–8.

    CAS  PubMed  Google Scholar 

  112. Hozyen FH, Ahmed HH, Essawy GE, Shalaby SI. Seasonal changes in some oxidant and antioxidant parameters during folliculogenesis in Egyptian buffalo. Anim Reprod Sci. 2014;151:131–6.

    Google Scholar 

  113. Kawaguchi S, Sakumoto R, Okuda K. Induction of the expressions of antioxidant enzymes by luteinizing hormone in the bovine corpus luteum. J Reprod Develop. 2013;59:219–24.

    CAS  Google Scholar 

  114. Behl R, Pandey RS. FSH induced stimulation of catalase activity in goat granulosa cells in vitro. Anim Reprod Sci. 2002;70:215–21.

    CAS  PubMed  Google Scholar 

  115. Park YS, You SY, Cho SS, Jeon HJ, Lee S, Cho DH, et al. Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes. Histochem Cell Biol. 2016;146:281–8.

    CAS  PubMed  Google Scholar 

  116. Mustacich D, Powis G. Thioredoxin reductase. Biochem J. 2000;346:1–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Rumbold A, Middleton P, Crowther C. Vitamin supplementation for preventing miscarriage (review). In: Cochrane Database Syst Rev; 2005. p. CD004073.

    Google Scholar 

  118. Di Cintio E, Parazzini F, Chatenoud L, Surace M, Benzi G, Zanconato G. Dietary factors and risk of spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. 2001;95:132–6.

    PubMed  Google Scholar 

  119. Shah PS, Ohlsson A. Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis. Can Med Assoc J. 2009;180:99–108.

    Google Scholar 

  120. Nimse SB, Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015;5:27986–8006.

    CAS  Google Scholar 

  121. Rengaraj D, Hong YH. Effects of dietary vitamin E on fertility functions in poultry species. Int J Mol Sci. 2015;16:9910–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science. 1922;56:650–1.

    CAS  PubMed  Google Scholar 

  123. Putnam ME, Comben N. Vitamin E. Vet Rec. 1987;121:541–5.

    CAS  PubMed  Google Scholar 

  124. De Vriese SR, Dhont M, Christophe AB. Oxidative stability of low density lipoproteins and vitamin E levels increase in maternal blood during normal pregnancy. Lipids. 2001;36:361–6.

    PubMed  Google Scholar 

  125. Chelchowska M, Laskowska-Klita T, Leibschang J. The effect of tobacco smoking during pregnancy on concentration of vitamin E in blood of mothers and their newborns in umbilical cord blood. Ginekol Pol. 2006;77:263–8.

    PubMed  Google Scholar 

  126. Lee E, Min SH, Song BS, Yeon JY, Kim JW, Bae JH, et al. Exogenous γ-tocotrienol promotes preimplantation development and improves the quality of porcine embryos. Reprod Fertil Dev. 2015;27:481–90.

    CAS  PubMed  Google Scholar 

  127. Mokhtar N, Rajikin MH, Zakaria Z. Role of tocotrienol-rich palm vitamin E on pregnancy and preimplantation embryos in nicotine treated rats. Biomed Res. 2008;19:181–4.

    CAS  Google Scholar 

  128. Rajikin MH, Latif ES, Mar MR, Mat Top AG, Mokhtar NM. Deleterious effects of nicotine on the ultrastructure of oocytes: role of gamma-tocotrienol. Med Sci Monit Basic Res. 2009;15:BR378–83.

    CAS  Google Scholar 

  129. Saleh H, Omar E, Froemming G, Said R. Tocotrienol preserves ovarian function in cyclophosphamide therapy. Hum Exp Toxicol. 2015;34:946–52.

    CAS  PubMed  Google Scholar 

  130. Saleh H, Omar E, Froemming G, Said R. Tocotrienol rich fraction supplementation confers protection on the ovary from cyclophasphamide induced apoptosis. Asian Pac J Trop Dis. 2014;4:234.

    Google Scholar 

  131. Thiyagarajan B, Valivittan K. Ameliorating effect of vitamin E on in vitro development of preimplantation buffalo embryos. J Assist Reprod Genet. 2009;26:217–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Natarajan R, Shankar MB, Munuswamy D. Effect of alpha-tocopherol supplementation on in vitro maturation of sheep oocytes and in vitro development of preimplantation sheep embryos to the blastocyst stage. J Assist Reprod Genet. 2010;27:483–90.

    PubMed  PubMed Central  Google Scholar 

  133. Kamsani YS, Rajikin MH, Nor Khan NAM, Satar NA, Chatterjee A. Nicotine-induced cessation of embryonic development is reversed by gamma-tocotrienol in mice. Med Sci Monit Basic Res. 2013;19:87–92.

    PubMed  PubMed Central  Google Scholar 

  134. Halliwell B, Gutteridge JM. The antioxidants of human extracellular fluids. Arch Biochem Biophys. 1990;280:1–8.

    CAS  PubMed  Google Scholar 

  135. Yang H. Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis. Biochem Genet. 2013;51:413–25.

    CAS  PubMed  Google Scholar 

  136. Luck MR, Jeyaseelan I, Scholes RA. Ascorbic acid and fertility. Biol Reprod. 1995;52:262–6.

    CAS  PubMed  Google Scholar 

  137. Paszkowski T, Clarke RN. The graafian follicle is a site of L-ascorbate accumulation. J Assist Reprod Genet. 1999;16:41–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Veek L. Atlas of the human oocyte and early conception. Baltimore: Williams & Wilkins; 1986.

    Google Scholar 

  139. Gai HF, An JX, Qian XY, Wei YJ, Williams JP, Gao GL. Ovarian damages produced by aerosolized fine particulate matter (PM2.5) pollution in mice: possible protective medications and mechanisms. Chin Med J. 2017;130:1400–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Tagler D, Makanji Y, Tu T, Bernabe BP, Lee R, Zhu J, et al. Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels. Biotechnol Bioeng. 2014;111:1417–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Saygin M, Ozmen O, Erol O, Ellidag HY, Ilhan I, Aslankoc R. The impact of electromagnetic radiation (2.45 Hz, Wi-Fi) on the female reproductive system: the role of vitamin C. Toxicol Ind Health. 2018;34:620–30.

    CAS  PubMed  Google Scholar 

  142. Wasserman RH, Corradino A. Metabolic role of vitamins A and D. Annu Rev Biochem. 1971;40:501–32.

    CAS  PubMed  Google Scholar 

  143. Olson JA. Vitamin A and carotenoids as antioxidants in a physiological context. J Nutr Sci Vitaminol. 1993;39:S57–65.

    CAS  PubMed  Google Scholar 

  144. Gad A, Hamed SA, Khalifa M, Amin A, El-Sayed A, Swiefy SA, et al. Retinoic acid improves maturation rate and upregulates the expression of antioxidant-related genes in in vitro matured buffalo (Bubalus bubalis) oocytes. Int J Vet Sci Med. 2018;6:279–85.

    PubMed  PubMed Central  Google Scholar 

  145. Guerin P, Mouatassim SE, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001;7:175–89.

    CAS  PubMed  Google Scholar 

  146. Pandey S, Srivastava R, Pandey S, Mukerjee D, Khattri S, Shanker K. Effect of vitamin “A” on free radical cascade in pregnancy induced hypertension. Boll Chim Farm. 2000;139:98–102.

    CAS  PubMed  Google Scholar 

  147. Livingston T, Eberhardt D, Edwards JL, Godkin J. Retinol improves bovine embryonic development in vitro. Reprod Biol Endocrinol. 2004;2:83.

    PubMed  PubMed Central  Google Scholar 

  148. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.

    CAS  PubMed  Google Scholar 

  149. Bhan I. Vitamin d binding protein and bone health. Int J Endocrinol. 2014;561214.

  150. Franasiak JM, Lara EE, Pellicer A. Vitamin D in human reproduction. Curr Opin Obstet Gynecol. 2017;29.

  151. Lerchbaum E, Rabe T. Vitamin D and female fertility. Curr Opin Obstet Gynecol. 2014;26:145–50.

    PubMed  Google Scholar 

  152. Shahrokhi SZ, Ghaffari F, Kazerouni F. Role of vitamin D in female reproduction. Clin Chim Acta. 2015. https://doi.org/10.1016/j.cca.2015.12.040.

  153. Muscogiuri G, Altieri B, de Angelis C, Palomba S, Pivonello R, Colao A. Shedding new light on female fertility: the role of vitamin D. Rev Endocr Metab Disord. 2017;18:273–83.

    CAS  PubMed  Google Scholar 

  154. Kwiecinksi GG, Petrie GI, DeLuca HF. 1,25-Dihydroxyvitamin D3 restores fertility of vitamin D-deficient female rats. Am J Phys. 1989;256:E483–7.

    CAS  Google Scholar 

  155. Kovacs CS, Woodland ML, Fudge NJ, Friel JK. The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab. 2005;289:E133–44.

    CAS  PubMed  Google Scholar 

  156. Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16:391–6.

    CAS  PubMed  Google Scholar 

  157. 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. Fertil Steril. 2010;94:1314–9.

    CAS  PubMed  Google Scholar 

  158. Paffoni A, Ferrari S, Vigano P, Pagliardini L, Papaleo E, Candiani M, et al. Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab. 2014;99:E2372–6.

    CAS  PubMed  Google Scholar 

  159. Garbedian K, Boggild M, Moody J, Liu KE. Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. CMAJ Open. 2013;1:E77–82.

    PubMed  PubMed Central  Google Scholar 

  160. Franasiak JM, Molinaro TA, Dubell EK, Scott KL, Ruiz JR, Forman EJ, et al. Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts. Am J Obstet Gynecol. 2015;212:315e1–6.

    Google Scholar 

  161. Neville G, Martyn F, Kilbane M, O’Riordan M, Wingfield M, McKenna M, et al. Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection. Int J Gynaecol Obstet. 2016;135:172–6.

    CAS  PubMed  Google Scholar 

  162. Arslan S, Akdevelioglu Y. The relationship between female reproductive functions and vitamin D. J Am Coll Nutr. 2018;37:546–51.

    CAS  PubMed  Google Scholar 

  163. Fiedor J, Fiedor L, Haessner R, Scheer H. Cyclic endoperoxides of β-carotene, potential pro-oxidants, as products of chemical quenching of singlet oxygen. Biochim Biophys Acta. 2005;1709:1–4.

    CAS  PubMed  Google Scholar 

  164. Krinsky NI, Johnson EJ. Carotenoid actions and their relation to health and disease. Mol Asp Med. 2005;26:459–516.

    CAS  Google Scholar 

  165. Strobel M, Tinz J, Biesalski HK. The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women. Eur J Nutr. 2007;46:I1–I20.

    PubMed  Google Scholar 

  166. Kramer MS, Kahn SR, Platt RW, Genest J, Rozen R, Chen MF, et al. Antioxidant vitamins, long-chain fatty acids, and spontaneous preterm birth. Epidemiology. 2009;20:707–13.

    PubMed  Google Scholar 

  167. Englund-Ogge L, Brantaeter AL, Sengpiel V, Haugen M, Birgisdottir BE, Myhre R, et al. Maternal dietary patterns and preterm delivery: results from large prospective cohort study. Br Med J. 2014;348:1446.

    Google Scholar 

  168. Bie JD, Langbeen A, Verlaet AAJ, Florizoone F, Imming I, Hermans N, et al. The effect of a negative energy balance status in beta-carotene availability in serum and follicular fluid of nonlactating dairy cows. J Dairy Sci. 2016;99:5808–19.

    PubMed  Google Scholar 

  169. Trojacanec S, Bobos S, Pajic M. Influence of beta-carotene and vitamin A supplementation on the ovarian activity of dairy cows with chronic fertility impairment. Veterinarski Arhiv. 2012;82:567–75.

    CAS  Google Scholar 

  170. Kulhan NG, Kulhan M, Turkler C, Ata N, Kiremitli T, Kiremitli S. Effect of lycopene on oxidative ovarian damage induced by cisplatin in rats. Gen Physiol Biophys. 2019;38:253–8.

    PubMed  Google Scholar 

  171. Turkler C, Onat T, Yildirim E, Kaplan S, Yazici GN, Mammadov R. An experimental study on the use of lycopene to prevent infertility due to acute oxidative ovarian damage caused by a single high dose of methotrexate. Adv Clin Exp Med. 2020;29:5–11.

    PubMed  Google Scholar 

  172. Vassiliadis S, Athanassakis I. A “conditionally essential” nutrient, L-carnitine, as a primary suspect in endometriosis. Fertil Steril. 2011;95:2759–60.

    CAS  PubMed  Google Scholar 

  173. Dunning KR, Robker RL. Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci. 2012;134:69–75.

    CAS  PubMed  Google Scholar 

  174. Aliabadi E, Soleimani Mehranjani M, Borzoei Z, Talaei-Khozani T, Mirkhani H, Tabesh H. Effects of L-carnitine and L-acetyl-carnitine on testicular sperm motility and chromatin quality. Iran J Reprod Med. 2012;10:77–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Dunning KR, Cashman K, Russell DL, Thompson JG, Norman RJ, Robker RL. Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biol Reprod. 2010;83:909–18.

    CAS  PubMed  Google Scholar 

  176. Abdelrazik H, Sharma R, Mahfouz R, Agarwal A. L-carnitine decreases DNA damage and improves the in vitro blastocyst development rate in mouse embryos. Fertil Steril. 2009;91:589–96.

    CAS  PubMed  Google Scholar 

  177. Ismail AM, Hamed AH, Saso S, Thabet HH. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2014;180:148–52.

    CAS  PubMed  Google Scholar 

  178. Samimi M, Jamilian M, Ebrahimi FA, Rahimi M, Tajbakhsh B, Asemi Z. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol. 2016;84:851–7.

    CAS  Google Scholar 

  179. Jamilian H, Jamilian M, Samimi M, Afshar Ebrahimi F, Rahimi M, Bahmani F, et al. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol. 2017;33:442–7.

    CAS  PubMed  Google Scholar 

  180. Genazzani AD, Lanzoni C, Ricchieri F, Santagni S, Rattighieri E, Chierchia E, et al. Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea. J Endocrinol Investig. 2011;34:287–91.

    CAS  Google Scholar 

  181. You J, Lee J, Hyun SH, Lee E. L-carnitine treatment during oocyte maturation improves in vitro development of cloned pig embryos by influencing intracellular glutathione synthesis and embryonic gene expression. Theriogenology. 2012;78:235–43.

    CAS  PubMed  Google Scholar 

  182. Mishra A, Reddy IJ, Gupta PS, Mondal S. L-carnitine mediated reduction in oxidative stress and alteration in transcript level of antioxidant enzymes in sheep embryos produced in vitro. Reprod Domest Anim. 2016;51:311–21.

    CAS  PubMed  Google Scholar 

  183. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine in female infertility. Reprod Biol Endocrinol. 2018;6:5.

    Google Scholar 

  184. Naziroglu M, Simsek M, Kutlu M. Moderate exercise with a dietary vitamin C and E combination protects against streptozotocin-induced oxidative damage to the blood and improves fetal outcomes in pregnant rats. Clin Chem Lab Med. 2004;42:511–7.

    CAS  PubMed  Google Scholar 

  185. Santanam N, Kavtaradze N, Murphy A, Dominguez C, Parthasarathy S. Antioxidant supplementation reduces endometriosis related pelvic pain in humans. Transl Res. 2013;161:189–95.

    CAS  PubMed  Google Scholar 

  186. Bhardwaj JK, Mittal M, Saraf P. Effective attenuation of glyphosate-induced oxidative stress and granulosa cell apoptosis by vitamins C and E in caprines. Mol Reprod Dev. 2018b;86:42–52.

    PubMed  Google Scholar 

  187. Zal F, Khademi F, Taheri R, Mostafavi-Pour Z. Antioxidant ameliorating effects against H2O2-induced cytotoxicity in primary endometrial cells. Toxicol Mech Methods. 2018;28:122–9.

    CAS  PubMed  Google Scholar 

  188. Abdel-Khalek AE, El-Ratel IT, Wafa WM, El-Nagar HA, Younan GE, Fouda SF. Effect of pre-conception coenzyme Q10 and L-carnitine treatments on ovulatory response, genital characteristics and in vitro embryo characteristics in rabbits. Asian J Anim Vet Adv. 2015;11:53–9.

    Google Scholar 

  189. Avci B, Bahadir A, Tuncel OK, Bilgici B. Influence of α-tocopherol and α-lipoic acid on bisphenol-A-induced oxidative damage in liver and ovarian tissue of rats. Toxicol Ind Health. 2016;32:1381–90.

    CAS  PubMed  Google Scholar 

  190. Hassan MSH, Youssef SF, El-bahy MA. Effects of L-carnitine and ascorbic acid supplementation on productive, reproductive, physiological and immunological performance of Golden Montazah laying hens. Egypt Poult Sci. 2011;31:557–78.

    Google Scholar 

  191. Scalbert A, Johnson IT, Saltmarsh M. Polyphenols: antioxidants and beyond. Am J Clin Nutr. 2005a;81:215S–7S.

    CAS  PubMed  Google Scholar 

  192. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005b;45:287–306.

    CAS  PubMed  Google Scholar 

  193. Ly C, Yockell-Lelievre J, Ferraro ZM, Arnason JT, Ferrier J, Gruslin A. The effects of dietary polyphenols on reproductive health and early development. Hum Reprod Update. 2015;21:228–48.

    CAS  PubMed  Google Scholar 

  194. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493–506.

    CAS  PubMed  Google Scholar 

  195. Rubiolo JA, Mithieux G, Vega FV. Resveratrol protects primary rat hepatocytes against oxidative stress damage: activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes. Eur J Pharmacol. 2008;591:66–72.

    CAS  PubMed  Google Scholar 

  196. Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun. 2003;309:1017–26.

    CAS  PubMed  Google Scholar 

  197. Liu M, Yin Y, Ye X, Zeng M, Zhao Q, Keefe DL, et al. Resveratrol protects against age-associated infertility in mice. Hum Reprod. 2013;28:707–17.

    CAS  PubMed  Google Scholar 

  198. Banu SK, Stanley JA, Sivakumar KK, Arosh JA, Burghardt RC. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol. Toxicol Appl Pharmacol. 2016;303:65–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Schube U, Nowicki M, Jogschies P, Blumenauer V, Bechmann I, Serke H. Resveratrol and desferoxamine protect human OxLDL-treated granulosa cell subtypes from degeneration. J Clin Endocrinol Metab. 2014;99:229–39.

    CAS  PubMed  Google Scholar 

  200. Atli M, Engin-Ustun Y, Tokmak A, Caydere M, Hucunenoglu S, Topcuoglu C. Dose dependent effect of resveratrol in preventing cisplastin-induced ovarian damage in rats: an experimental study. Reprod Biol. 2017;17:274–80.

    PubMed  Google Scholar 

  201. Kolesarova A, Capcarova M, Maruniakova N, Lukac N, Ciereszko RE, Sirotkin AV. Resveratrol inhibits reproductive toxicity induced by deoxynivalenol. J Environ Sci Heal A. 2012;47:1329–34.

    CAS  Google Scholar 

  202. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med. 1992;21:334–50.

    CAS  PubMed  Google Scholar 

  203. Roychoudhury S, Agarwal A, Virk G, Cho CL. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod BioMed Online. 2017;34:487–98.

    CAS  PubMed  Google Scholar 

  204. Rahman SU, Huang Y, Zhu L, Feng S, Khan IM, Wu J, et al. Therapeutic role of green tea polyphenols in improving fertility: a review. Nutrients. 2018;10:834.

    PubMed Central  Google Scholar 

  205. Wang ZG, Yu SD, Xu ZR. Improvement in bovine embryo production in vitro by treatment with green tea polyphenols during in vitro maturation of oocytes. Anim Reprod Sci. 2007;100:22–31.

    CAS  PubMed  Google Scholar 

  206. Roth Z, Aroyo A, Yavin S, Arav A. The antioxidant epigallocatechin gallate (EGCG) moderates the deleterious effects of maternal hyperthermia on follicle-enclosed oocytes in mice. Theriogenology. 2008;70:887–97.

    CAS  PubMed  Google Scholar 

  207. Barakat IA, Al-Himaidi AR, Rady AM. Antioxidant effect of green tea leaves extract on in vitro production of sheep embryos. Pak J Zool. 2014;46:167–75.

    Google Scholar 

  208. Matsuzaki S, Darcha C. Antifibrotic properties of epigallocatechin-3-gallate in endometriosis. Hum Reprod. 2014;29:1677–87.

    CAS  PubMed  Google Scholar 

  209. Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol. 2014;39:113–204.

    CAS  PubMed  Google Scholar 

  210. Fan X, Zhang C, Liu DB, Yan J, Liang HP. The clinical applications of curcumin: current state and the future. Curr Pharm Des. 2013;19:2011–31.

    CAS  PubMed  Google Scholar 

  211. Stanic Z. Curcumin, a compound from natural sources, a true scientific challenge – a review. Plant Foods Hum Nutr. 2017;72:1–12.

    CAS  PubMed  Google Scholar 

  212. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1–7.

    CAS  PubMed  Google Scholar 

  213. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003;9:161–8.

    PubMed  Google Scholar 

  214. Voznesens’ka T, Bryzhina TM, Sukhina VS, Makohon NV, Aleksieieva IM. Effect of NF-kappaB activation inhibitor curcumin on the oogenesis and follicular cell death in immune ovarian failure in mice. Fiziol Zh. 2010;56:96–101.

    PubMed  Google Scholar 

  215. Aktas C, Kanter M, Kocak Z. Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. Toxicol Ind Health. 2012;28:852–63.

    CAS  PubMed  Google Scholar 

  216. Alekseyeva IN, Makogon NV, Bryzgina TM, Voznesenskaya TY, Sukhina VS. Effects of NF-κB blocker curcumin on oogenesis and immunocompetent organ cells in immune ovarian injury in mice. B Exp Biol Med. 2011;151:432–5.

    CAS  Google Scholar 

  217. Tiwari-Pandey R, Ram-Sairam M. Modulation of ovarian structure and abdominal obesity in curcumin- and flutamide-treated aging FSH-R haploinsufficient mice. Reprod Sci. 2009;16:539–50.

    CAS  PubMed  Google Scholar 

  218. Sirotkin AV, Kadasi A, Stochmalova A, Balazi A, Foldesiova M, Makovicky P, et al. Effect of turmeric on the viability, ovarian folliculogenesis, fecundity, ovarian hormones and response to luteinizing hormone of rabbits. Animal. 2018;12:1242–9.

    CAS  PubMed  Google Scholar 

  219. Itthipanichpong C, Ruangrungs N, Kemsri W, Sawasdipanich A. Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat uterus. J Med Assoc Thail. 2003;2S:299–309.

    Google Scholar 

  220. Yan Z, Dai Y, Fu H, Zheng Y, Bao D, Yin Y, et al. Curcumin exerts a protective effect against premature ovarian failure in mice. J Mol Endocrinol. 2018;60:261–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  221. Middleton EJ, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol. 1992;43:1167–79.

    CAS  PubMed  Google Scholar 

  222. Sesso HD, Gaziano JM, Liu S, Buring JE. Flavonoid intake and risk of cardiovascular disease in women. Am J Clin Nutr. 2003;77:1400–8.

    CAS  PubMed  Google Scholar 

  223. Yang T, Kong B, Gu JW, Kuang Y, Cheng L, Yang W, et al. Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury. Cell Mol Neurobiol. 2014;34:797–804.

    CAS  PubMed  Google Scholar 

  224. Dusza L, Ciereszko R, Skarzynski DJ, Nogowski L, Opalka M, Kaminska B, et al. Mechanism of phytoestrogens action in reproductive processes of mammals and birds. Reprod Biol. 2006;6:151–74.

    PubMed  Google Scholar 

  225. Santini SE, Basini G, Bussolati S, Grasseli F. The phytoestrogen quercetin impairs steroidogenesis and angiogenesis in swine granulosa cells in vitro. J Biomed Biotechnol. 2009;419891.

  226. Yu S, Long H, Lyu QF, Zhang QH, Yan ZG, Liang HX, et al. Protective effect of quercetin on the development of preimplantation mouse embryos against hydrogen peroxide-induced oxidative injury. PLoS One. 2014;9:e89520.

    PubMed  PubMed Central  Google Scholar 

  227. Wang J, Qian X, Gao Q, Lv C, Xu J, Jin H. Quercetin increases the antioxidant capacity of the ovary in menopausal rats and in ovarian granulosa cell culture in vitro. J Ovarian Res. 2018;11:51.

    PubMed  PubMed Central  Google Scholar 

  228. Nna VU, Usman UZ, Ofutet EO, Owu DU. Quercetin exerts preventive effects on cadmium chloride-induced oxidative stress in the uterus and ovaries of female Wistar rats. Food Chem Toxicol. 2017;102:143–55.

    CAS  PubMed  Google Scholar 

  229. Jia Y, Lin J, Mi Y, Zhang C. Quercetin attenuates cadmium-induced oxidative damage and apoptosis in granulosa cells from chicken ovarian follicles. Reprod Toxicol. 2011;31:477–85.

    CAS  PubMed  Google Scholar 

  230. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr. 1997;17:353–81.

    CAS  PubMed  Google Scholar 

  231. Carbonel AAF, Simoes RS, Girao JHC, da Silva Sesso GR, Bertoncini CRA, Sorpreso ICE, et al. Isoflavones in gynecology. Rev Assoc Med Bras. 2018;64:560–4.

    PubMed  Google Scholar 

  232. Adlercreutz H, Mousavi Y, Clark J, Hockersted K, Hamalainen EK, Wahala K, et al. Dietary phytoestrogens and cancer: in vitro and in vivo studies. J Steroid Biochem Mol Biol. 1992;41:331–7.

    CAS  PubMed  Google Scholar 

  233. Dechaud H, Ravard C, Claustrat F. Brac de la Perriere A. Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG). Steroids. 1999;64:328–34.

    CAS  PubMed  Google Scholar 

  234. Evans BA, Griffiths K, Morton MS. Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol. 1995;147:295–302.

    CAS  PubMed  Google Scholar 

  235. Wang C, Makela T, Hase TA, Adlercreutz CHT, Kurzer MS. Lignans and isoflavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol. 1994;50:205–12.

    CAS  PubMed  Google Scholar 

  236. Pelissero C, Lenczowski M, Chinzi D, Davail-Cuisset B, Sumpter J, Fostier A. Effects of flavonoids on aromatase activity, and in vitro study. J Steroid Biochem Mol Biol. 1996;57:215–23.

    CAS  PubMed  Google Scholar 

  237. Chen S, Kao YC, Laughton CA. Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase. J Steroid Biochem Mol Biol. 1997;61:107–15.

    CAS  PubMed  Google Scholar 

  238. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010;31:400–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  239. Lee JY, Kim HS, Song YS. Genisten as a potential anticancer agent against ovarian cancer. J Tradit Complement Med. 2012;2:96–104.

    PubMed  PubMed Central  Google Scholar 

  240. Zhuang XL, Fu YC, Xu JJ, Kong XX, Chen ZG, Luo LL. Effects of genistein on ovarian follicular development and ovarian lifespan in rats. Fitoterapia. 2010;81:998–1002.

    CAS  PubMed  Google Scholar 

  241. Medigovic I, Ristic N, Trifunovic S, Manojlovic-Stojanoski M, Milosevic V, Zikic D, et al. Genistein affects ovarian folliculogenesis: a stereological study. Microsc Res Tech. 2012;75:1691–9.

    CAS  PubMed  Google Scholar 

  242. Saleh DO, Mansour DF. Ovario-protective effects of genistein against cyclophosphamide toxicity in rats: role of anti-müllerian hormone and oestradiol. Eur J Pharmacol. 2016;789:163–71.

    CAS  PubMed  Google Scholar 

  243. Tsuchiya M, Miura T, Hanaoka T, Iwasaki M, Sasaki H, Tanaka T, et al. Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism. Epidemiology. 2007;18:402–8.

    PubMed  Google Scholar 

  244. Carbonel AA, Simoes RS, Santos RH, Baracat MC, Simoes Mde J, Baracat EC, et al. Effects of high-dose isoflavones on rat uterus. Rev Assoc Med Bras. 2011;57:534–9.

    PubMed  Google Scholar 

  245. Carbonel AAF, Lima PDA, Lim JJ, Fuchs LFP, Paiotti APR, Sasso GRDS, et al. The effects of soybean isoflavones and 17β-estradiol in uterus and mammary glands of diabetic rat models. Gynecol Endocrinol. 2018;34:314–9.

    CAS  PubMed  Google Scholar 

  246. Quaas AM, Kono N, Mack WJ, Hodis HN, Felix JC, Paulson RJ, et al. Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women: a randomized controlled trial. Menopause. 2013;20:840–4.

    PubMed  PubMed Central  Google Scholar 

  247. Atanasov AG, Waltenberger B, Pferschy-Wenzig E-M, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015;33:1582–614.

    CAS  PubMed  PubMed Central  Google Scholar 

  248. Towns AM, Eyi SM, van Andel T. Traditional medicine and childcare in western Africa: mothers’ knowledge, folk illnesses, and patterns of healthcare-seeking behavior. PLoS One. 2014;9:e105972.

    PubMed  PubMed Central  Google Scholar 

  249. Licata M, Tuttolomondo T, Leto C, Virga G, Bonsangue G, Cammalleri I, et al. A survey of wild plant species for food use in Sicily (Italy)–results of a 3-year study in four regional parks. J Ethnobiol Ethnomed. 2016;12:12.

    PubMed  PubMed Central  Google Scholar 

  250. Kaadaaga HF, Ajeani J, Ononge S, Alele PE, Nakasujja N, Manabe YC, et al. Prevalence and factors associated with use of herbal medicine among women attending an infertility clinic in Uganda. BMC Complement Altern Med. 2014;14:27.

    PubMed  PubMed Central  Google Scholar 

  251. Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environ Health Perspect. 2001;109:69–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  252. Telefo PB, Lienou LL, Yemele MD, Lemfack MC, Mouokeu C, Goka CS, et al. Ethnopharmacological survey of plants used for the treatment of female infertility in Baham. Cameroon J Ethnopharmacol. 2011;136:178–87.

    CAS  PubMed  Google Scholar 

  253. Akour A, Kasabri V, Afifi FU, Bulatova N. The use of medicinal herbs in gynecological and pregnancy-related disorders by Jordanian women: a review of folkloric practice vs. evidence-based pharmacology. Pharm Biol. 2016;54:1901–18.

    PubMed  Google Scholar 

  254. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine. 2004;11:56e64.

    Google Scholar 

  255. Bourgou S, Pichette A, Marzouk B, Legault J. Bioactivities of black cumin essential oil and its main terpenes from Tunisia. S Afr J Bot. 2010;76:210e216.

    Google Scholar 

  256. Mukhallad AM, Mohamad MJM, Hatham D. Effects of black seeds (Nigella sativa) on spermatogenesis and fertility of male albino rats. Res J Medicine & Med Sci. 2009;4(2):386–90.

    Google Scholar 

  257. Alenzi FQ, El-Bolkiny YS, Salem ML. Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. Br J Biomed Sci. 2010;67(1):20–8.

    CAS  PubMed  Google Scholar 

  258. Kanter M. Thymoquinone reestablishes spermatogenesis after testicular injury caused by chronic toluene exposure in rats. Toxicol Ind Health. 2011;27:155–66.

    CAS  PubMed  Google Scholar 

  259. Naeimi SA, Tansaz M, Sohrabvand F, Hajimehdipoor H, Nabimeybodi R, Saber S, et al. Assessing the effect of processed nigella sativa on oligomenorrhea and amenorrhea in patients with polycystic ovarian syndrome: a pilot study. Int J Pharm Sci Res. 2018;9(11):4716–22.

    CAS  Google Scholar 

  260. Arak JK, Assi MA. Effect of Nigella sativa L. seeds on ovaries function in adult rats treated with lead acetate. Al-Anbar Medical J. 2011;9(1):59–70.

    Google Scholar 

  261. Kamarzaman S, Shaban M, AbdulRahman S. The prophylactic effect of Nigella sativa against cyclophosphamide in the ovarian follicles of matured adult mice: a preliminary study. J Animal Plant Sci. 2014;24:81–8.

    Google Scholar 

  262. Shahin AY, Ismail AM, Zahran KM, Makhlouf A. Adding phytoestrogens to clomiphene induction in unexplained infertility – a randomized trial. Reprod BioMed Online. 2008;16:580–8.

    CAS  PubMed  Google Scholar 

  263. Brinker F. The toxicology of botanical medicines. Sandy, Oregon: Eclectic Medical Publications; 2000.

    Google Scholar 

  264. Jellin JM, Batz F, Hitchens K. Natural medicines comprehensive database. Stockton, CA: Therapeutic Research Faculty. 2004;1530.

  265. Hernandez Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas. 2003;44:S59–65.

    PubMed  Google Scholar 

  266. Shahin AY, Ismail AM, Shaaban OM. Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol–a randomized trial. Reprod BioMed Online. 2009;19:501–7.

    CAS  PubMed  Google Scholar 

  267. Shahin AY, Mohammed SA. Adding the phytoestrogen Cimicifugae racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates–a randomized trial. Gynecol Endocrinol. 2014;30(7):505–10.

    CAS  PubMed  Google Scholar 

  268. Kamel HH. Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;168(1):60–3.

    CAS  PubMed  Google Scholar 

  269. Ranasinghe P, Pigera S, Premakumara GA, Galappaththy P, Constantine GR, Katulanda P. Medicinal properties of ‘true’ cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complement Altern Med. 2013;22:13e275.

    Google Scholar 

  270. Yuce A, Turk G, Ceribasi S, Sonmez M, Ciftci M, Guvenc M. Effects of cinnamon (Cinnamomum zeylanicum) bark oil on testicular antioxidant values, apoptotic germ cell and sperm quality. Andrologia. 2013;45(4):248–55.

    CAS  PubMed  Google Scholar 

  271. Sariozkan S, Turk G, Guvenc M, Yuce A, Ozdamar S, Canturk F, et al. Effects of cinnamon (C. zeylanicum) bark oil against taxanes-induced damages in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular apoptosis, and sperm DNA integrity. Nutr Cancer. 2016;68(3):481–94.

    CAS  PubMed  Google Scholar 

  272. Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res Clin Pract. 2003;62:139–48.

    PubMed  Google Scholar 

  273. Cao H, Graves DJ, Anderson RA. Cinnamon extract regulates glucose transport and insulin-signaling gene expression in mouse adipocytes. Phytomedicine. 2010;17:1027–32.

    CAS  PubMed  Google Scholar 

  274. Borzoei A, Rafraf M, Niromanesh S, Farzadi L, Narimani F, Doostan F. Effects of cinnamon supplementation on antioxidant status and serum lipids in women with polycystic ovary syndrome. J Tradit Complement Med. 2017;8:128–33.

    PubMed  PubMed Central  Google Scholar 

  275. Malviya KG, Bhabulkar MW, Mali PY, Rangari D. Evaluation of analgesic potential of TFG seeds in rats by using tail flick method. J Pharm Res. 2010;3:1680–1.

    Google Scholar 

  276. Rohini R. Diuretic effect of Trigonella foenum graecum seed extracts. Int J Alternat Med. 2009;6(2):1–4.

    Google Scholar 

  277. Maheshwari A, Verma N, Swaroop A, Bagchi M, Preuss HG, Tiwari K, et al. Efficacy of Furosap™, a novel Trigonella foenum-graecum seed extract, in enhancing testosterone level and improving sperm profile in male volunteers. Int J Med Sci. 2017;14(1):58–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  278. Rao A, Steels E, Beccaria G, Inder WJ, Vitetta L. Influence of a specialized Trigonella foenum-graecum seed extract (Libifem), on testosterone, estradiol and sexual function in healthy menstruating women, a randomised placebo controlled study. Phytother Res. 2015;29(8):1123–30.

    PubMed  Google Scholar 

  279. Swaroop A, Jaipuriar AS, Gupta SK, Bagchi M, Kumar P, Preuss HG, et al. Efficacy of a novel fenugreek seed extract (Trigonella foenum-graecum, Furocyst™) in polycystic ovary syndrome (PCOS). Int J Med Sci. 2015;12:825–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  280. Inanmdar W, Sultana A, Mubeen U, Rahman K. Clinical efficacy of Trigonella foenum graecum (Fenugreek) and dry cupping therapy on intensity of pain in patients with primary dysmenorrheal. Chin J Integr Med. https://doi.org/10.1007/s11655-016-2259-x.

  281. Guimaraes R, Barros L, Carvalho AM, Ferreira I. Infusions and decoctions of mixed herbs used in folk medicine: synergism in antioxidant potential. Phytother Res. 2011;25(8):1209–14.

    PubMed  Google Scholar 

  282. Escop M. The scientific foundation for herbal medicinal products [M]. German: Thieme Medical Publishers; 2003. p. 429–36.

    Google Scholar 

  283. Salehi M, Setayesh M, Mokaberinejad R. Treatment of recurrent ovarian cysts and primary infertility by Iranian traditional medicine: a case report. J Evid Based Complementary Altern Med. 2017;22(3):374–7.

    PubMed  Google Scholar 

  284. 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. Asian J Clin Case Reports Tradition Alternative Med. 2017;1:43–50.

    Google Scholar 

  285. Mokaberinejad R, Rampisheh Z, Aliasl J, Akhtari E. The comparison of fennel infusion plus dry cupping versus metformin in management of oligomenorrhoea in patients with polycystic ovary syndrome: a randomised clinical trial. J Obstet Gynaecol. 2019;39(5):652–8.

    PubMed  Google Scholar 

  286. Telefo PB, Tagne SR, Koona OES, Yemele DM, Tchouanguep FM. Effect of the aqueous extract of Justicia insularis T. Anders (Acanthaceae) on ovarian folliculogenesis and fertility of female rats. Afr J Tradit Complement Altern Med. 2012;9:197–203.

    PubMed  Google Scholar 

  287. da Rocha CF, de Medeiros Souza Lima Y, Carvalho HO, Pinto RC, Ferreira IM, Castro AN, et al. Action of the hydroethanolic extract of the flowers of Acmella oleracea (L.) R.K. Jansen on the reproductive performance of Wistar female rats: a popular female aphrodisiac from the Amazon. J Ethnopharmacol. 2018;214:301–8.

    PubMed  Google Scholar 

  288. Abbas MA, Taha MO, Zihlif MA, Disi AM. β-Caryophyllene causes regression of endometrial implants in a rat model of endometriosis without affecting fertility. Eur J Pharmacol. 2013;702:12–9.

    CAS  PubMed  Google Scholar 

  289. Ansari AS, Sevliya K, Mohammad I, Badar A, Lohiya NK. Plants for female fertility regulation: a review. J Pharmacol Toxicol. 2017;12:57–75.

    CAS  Google Scholar 

  290. Gupta S, Sekhon L, Kim Y, Agarwal A. The role of oxidative stress and antioxidants in assisted reproduction. Curr Women’s Health Rev. 2010;6:227–38.

    CAS  Google Scholar 

  291. Brezina PR, Zhao Y. The ethical, legal, and social issues impacted by modern assisted reproductive technologies. Obstet Gynecol Int. 2012;686253.

  292. Agarwal A, Majzoub A. Role of antioxidants in assisted reproductive techniques. World J Mens Health. 2017;35:77–93.

    PubMed  PubMed Central  Google Scholar 

  293. du Plessis SS, Makker K, Desai NR, Agarwal A. Impact of oxidative stress on IVF. Expet Rev Obstet Gynecol. 2008;3:539–54.

    Google Scholar 

  294. Agarwal A, Durairajanayagam D, du Plessis SS. Utility of antioxidants during assisted reproductive techniques: an evidence based review. Reprod Biol Endocrinol. 2014;12:112.

    PubMed  PubMed Central  Google Scholar 

  295. Lu X, Wu Z, Wang M, Cheng W. Effects of vitamin C on the outcome of in vitro fertilization–embryo transfer in endometriosis: a randomized controlled study. J Int Med Res. 2018;46:4624–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  296. Esmaiel S, Tahereh H, Noreddin NMS, Massood E. Mancozeb exposure during development and lactation periods results in decreased oocyte maturation, fertilization rates, and implantation in the first-generation mice pups: protective effect of vitamins E and C. Toxicol Ind Health. 2019;35:714–25.

    PubMed  Google Scholar 

  297. Griesinger G, Franke K, Kinast C, Kutzelnigg A, Riedinger S, Kulin S, et al. Ascorbic acid supplement during luteal phase in IVF. J Assist Reprod Genet. 2002;19:164–8.

    PubMed  PubMed Central  Google Scholar 

  298. Henmi H, Endo T, Kitajima Y, Manase K, Hata H, Kudo R. Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect. Fertil Steril. 2003;80:459–61.

    PubMed  Google Scholar 

  299. Cicek N, Eryilmaz OG, Sarikaya E, Gulerman C, Genc Y. Vitamin E effect on controlled ovarian stimulation of unexplained infertile women. J Assist Reprod Genet. 2012;29:325–8.

    PubMed  PubMed Central  Google Scholar 

  300. Fatemi F, Mohammadzadeh A, Sadegh 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. Clin Nutr ESPEN. 2017;18:23–30.

    PubMed  Google Scholar 

  301. Rimoldi SF, Sartori C, Rexhaj E, Bailey DM, de Marchi SF, McEneny J, et al. Antioxidants improve vascular function in children conceived by assisted reproductive technologies: a randomized double-blind placebo-controlled trial. Eur J Prev Cardiol. 2015;22:1399–407.

    PubMed  Google Scholar 

  302. Gaskins AJ, Afeiche MC, Wright DL, Toth TL, Williams PL, Gillman MW, et al. Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet Gynecol. 2014;124:801–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  303. Kim MK, Park JK, Paek SK, Kim JW, Kwak IP, Lee HJ, et al. Effects and pregnancy outcomes of L-carnitine supplementation in culture media for human embryo development from in vitro fertilization. J Obstet Gynaecol Res. 2018;44:2059–66.

    CAS  PubMed  Google Scholar 

  304. Jiang WJ, Yao XR, Zhao YH, Gao QS, Jin QG, Li YH, et al. L-carnitine prevents bovine oocyte aging and promotes subsequent embryonic development. J Reprod Dev. 2019;65(6):499–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  305. Elomda AM, Saad MF, Saeed AM, Elsayed A, Abass AO, Safaa HM, et al. Antioxidant and developmental capacity of retinol on the in vitro culture of rabbit embryos. Zygote. 2018;26:326–32.

    CAS  PubMed  Google Scholar 

  306. Wang Y, Zhang M, Chen ZJ, Du Y. Resveratrol promotes the embryonic development of vitrified mouse oocytes after in vitro fertilization. In Vitro Cell Dev Biol Anim. 2018;54:430–8.

    CAS  PubMed  Google Scholar 

  307. Elgindy EA, El-Huseiny AM, Mostafa MI, Gaballah AM, Ahmed TA. N-acetyl cysteine: could it be an effective adjuvant therapy in ICSI cycles? A preliminary study. Reprod BioMed Online. 2011;20:789–96.

    Google Scholar 

  308. Huang CC, Tien YJ, Chen MJ, Chen CH, Ho HN, Yang YS. Symptom patterns and phenotypic subgrouping of women with polycystic ovary syndrome: association between endocrine characteristics and metabolic aberrations. Hum Reprod. 2015;30:937–46.

    CAS  PubMed  Google Scholar 

  309. Izadi A, Ebrahimi S, Shirzai S, Taghizadeh S, Parizad M, Farzadi L, et al. Hormonal and metabolic effects of coenzyme Q10 and/or vitamin E in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2019;104:319–27.

    PubMed  Google Scholar 

  310. Olaniyan OT, Femi A, Iliya G, Ayobami D, Godam E, Olugbenga E, et al. Vitamin C suppresses ovarian pathophysiology in experimentalpolycystic ovarian syndrome. Pathophysiology. 2019;26:331–41.

    CAS  PubMed  Google Scholar 

  311. Kalhori Z, Mehranjani MS, Azadbakht M, Shariatzadeh MA. L-Carnitine improves endocrine function and folliculogenesis by reducing inflammation, oxidative stress and apoptosis in mice following induction of polycystic ovary syndrome. Reprod Fertil Dev. 2019;31:282–93.

    CAS  PubMed  Google Scholar 

  312. Banaszewska B, Wrotynska-Barczynska J, Spaczynski RZ, Pawelczyk L, Duleba AJ. Effects of resveratrol on polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2016;101:3575–81.

    Google Scholar 

  313. Ostadmohammadi V, Jamilian M, Bahmani F, Asemi Z. Vitamin D and probiotic cosupplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome. J Ovarian Res. 2019;12:5.

    PubMed  PubMed Central  Google Scholar 

  314. Jahan S, Abid A, Khalid S, Afsar T, Ain QU, Shaheen G, et al. Therapeutic potentials of quercetin in management of polycystic ovarian syndrome using letrozole induced rat model: a histological and a biochemical study. J Ovarian Res. 2018;11:26.

    PubMed  PubMed Central  Google Scholar 

  315. Hong Y, Yin Y, Tan Y, Hong K, Jiang F, Wang Y. Effect of quercetin on biochemical parameters in letrozole-induced polycystic ovary syndrome in rats. Trop J Pharm Res. 2018;17:1783–8.

    CAS  Google Scholar 

  316. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–9.

    CAS  PubMed  Google Scholar 

  317. Langendonckt AV, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril. 2002;77:861–70.

    PubMed  Google Scholar 

  318. Sinha A, Gupta S. The role of antioxidant supplementation in endometriosis therapy. J Gynecol Women’s Health. 2017;3.

  319. Erten OU, Ensari TGA, Dilbaz B, Cakiroglu H, Altinbas SK, Caydere M, et al. Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis. Taiwan J Obstet Gynecol. 2015;55:251–7.

    Google Scholar 

  320. Darling AM, Chavarro JE, Malspeis S, Harris HR, Missmer SA. A prospective cohort study of vitamins B, C, E, and multivitamin intake and endometriosis. J Endometr. 2013;5:17–26.

    PubMed  PubMed Central  Google Scholar 

  321. Wang CC, Xu H, Man GCW, Zhang T, Chu KO, Chu CY, et al. Prodrug of green tea epigallocatechin-3-gallate (pro-EGCG) as a potent anti-angiogenesis agent for endometriosis in mice. Angiogenesis. 2013;16:59–69.

    CAS  PubMed  Google Scholar 

  322. Jana SK, Chakravarty B, Chaudhury K. Letrozole and curcumin loaded-PLGA nanoparticles: a therapeutic strategy for endometriosis. J Nanomed Biother Discov. 2014;4:1.

    Google Scholar 

  323. Durak Y, Kokcu A, Kefeli M, Bildircin D, Celik H, Alper T. Effect of vitamin C on the growth of experimentally induced endometriotic cysts. J Obstet Gynaecol Res. 2013;39:1253–8.

    PubMed  Google Scholar 

  324. Mier-Cabrera J, Genera-Garcia M, De la Jara-Diaz J, Perichart-Perera O, Vadillo-Ortega F, HernandezGuerrero C. Effect of vitamins C and E supplementation on peripheral oxidative stress markers and pregnancy rate in women with endometriosis. Int J Gynaecol Obstet. 2008;100:252–6.

    CAS  PubMed  Google Scholar 

  325. Mier-Cabrera J, Aburto-Soto T, Burrola-Mendez S, Jimenez-Zamudio L, Tolentino MC, Casanueva E, et al. Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet. Reprod Biol Endocrinol. 2009;7:54.

    PubMed  PubMed Central  Google Scholar 

  326. Sharma JB, Ashok K, Kumar A, Malhotra M, Arora R, Prasad S, et al. Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas. Int J Gynaecol Obstet. 2003;81:257–62.

    CAS  PubMed  Google Scholar 

  327. Antartani R, Ashok K. Effect of lycopene in prevention of preeclampsia in high risk pregnant women. J Turk Ger Gynecol Assoc. 2011;12:35–8.

    PubMed  PubMed Central  Google Scholar 

  328. Hauth JC, Clifton RG, Roberts JM, Spong CY, Myatt L, Leveno KJ, et al. Vitamin C and E supplementation to prevent spontaneous preterm birth. Obstet Gynecol. 2010;116:653–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  329. Samimi M, Foroozanfard F, Amini F, Sehat M. Effect of vitamin D supplementation on unexplained recurrent spontaneous abortion: a double-blind randomized controlled trial. Global J Health Sci. 2017;9:95.

    Google Scholar 

  330. Rumbold A, Duley L, Crowther C, Haslam R. Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev. 2005;4:CD004227.

    Google Scholar 

  331. Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362:1282–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  332. Xu H, Perez-Cuevas R, Xiong X, Reyes H, Roy C, Julien P, et al. An international trial of antioxidants in the prevention of preeclampsia (INTAPP). Am J Obstet Gynecol. 2010;202:239e1–239e10.

    Google Scholar 

  333. Klemmensen A, Tabor A, Osterdal ML, Knudsen VK, Halldorsson TI, Mikkelsen TB, et al. Intake of vitamin C and E in pregnancy and risk of pre-eclampsia: prospective study among 57,346 women. BJOG. 2009;116:964–74.

    CAS  PubMed  Google Scholar 

  334. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006;367:1145–54.

    CAS  PubMed  Google Scholar 

  335. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens Pregnancy. 2009;28:417–34.

    CAS  PubMed  Google Scholar 

  336. Chen CC, Chan WH. Injurious effects of curcumin on maturation of mouse oocytes, fertilization and fetal development via apoptosis. Int J Mol Sci. 2012;13:4655–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  337. Jacobsen BK, Jaceldo-Siegl K, Knutsen SF, Fan J, Oda K, Fraser GE. Soy isoflavone intake and the likelihood of ever becoming a mother: the Adventist Health Study-2. Int J Women's Health. 2014;6:377–84.

    Google Scholar 

  338. Jefferson WN, Couse JF, Padilla-Banks E, Korach KS, Newbold RR. Neonatal exposure to genistein induces estrogen receptor (ER) alpha expression and multioocyte follicles in the maturing mouse ovary: evidence for ERbeta-mediated and nonestrogenic actions. Biol Reprod. 2002;67:1285–96.

    CAS  PubMed  Google Scholar 

  339. Iguchi T, Fukazawa Y, Uesugi Y, Takasugi N. Polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol in vivo and in vitro. Biol Reprod. 1990;43:478–84.

    CAS  PubMed  Google Scholar 

  340. Amir AA, Kelly JM, Kleemann DO, Durmic Z, Blache D, Martin GB. Phyto-oestrogens affect fertilisation and embryo development in vitro in sheep. Reprod Fertil Dev. 2018;30:1109–15.

    CAS  PubMed  Google Scholar 

  341. Qazan WS. Effects of short and long term treatment of Ballota undulata on female albino rats fertility and pregnancy. Pak J Biol Sci. 2008;11:638–42.

    PubMed  Google Scholar 

  342. Priya G, Saravanan K, Renuka C. Medicinal plants with potential antifertility activity-a review of sixteen years of herbal medicine research (1994–2010). Int J Pharm Tech Res. 2014;4:481–94.

    Google Scholar 

  343. Mannion C, Mansell D. Breastfeeding self-efficacy and the use of prescription medication: a pilot study. Obstet Gynecol Int. 2012;562704.

  344. Chen J, Guo Q, Pei Y, Ren Q, Chi L, Hu R, 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 Womens Health. 2020;20(1):69.

    CAS  PubMed  PubMed Central  Google Scholar 

  345. Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies – a report of 20 cases. Hum Fertil (Camb). 2009;12(4):198–203.

    CAS  Google Scholar 

  346. El Sharkwy I, El-Din MS. l-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial. Gynecol Endocrinol. 2019;35(8):701–5.

    PubMed  Google Scholar 

  347. El Sharkwy IA, El Aziz WMA. Randomized controlled trial of N-acetylcysteine versus l-carnitine among women with clomiphene-citrate-resistant polycystic ovary syndrome. Int J Gynaecol Obstet. 2019;147(1):59–64.

    PubMed  Google Scholar 

  348. Bahramrezaie M, Amidi F, Aleyasin A, Saremi AT, Aghahoseini M, Brenjian S, et al. Effects of resveratrol on VEGF & HIF1 genes expression in granulose cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial. J Assist Reprod Genet. 2019;36(8):1701–12.

    PubMed  PubMed Central  Google Scholar 

  349. Kodarahmian M, Amidi F, Moini A, Kashani L, Nashtaei MS, Pazhohan A, et al. The modulating effects of resveratrol on the expression of MMP-2 and MMP-9 in endometriosis women: a randomized exploratory trial. Gynecol Endocrinol. 2019;35(8):719–26.

    CAS  PubMed  Google Scholar 

  350. Ricci AG, Olivares CN, Bilotas MA, Baston JI, Singla JJ, Meresman GF, et al. Natural therapies assessment for the treatment of endometriosis. Hum Reprod. 2013;28(1):178–88.

    CAS  PubMed  Google Scholar 

  351. Khorshidi M, Moini A, Alipoor E, Rezvan N, Gorgani-Firuzjaee S, Yaseri M, et al. The effects of quercetin supplementation on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome. Phytother Res. 2018;32(11):2282–9.

    CAS  PubMed  Google Scholar 

  352. Rezvan N, Moini A, Janani L, Mohammad K, Saedisomeolia A, Nourbakhsh M, et al. Effects of quercetin on adiponectin-mediated insulin sensitivity in polycystic ovary syndrome: a randomized placebo-controlled double-blind clinical trial. Horm Metab Res. 2017;49(2):115–21.

    CAS  PubMed  Google Scholar 

  353. Moreira-Pinto B, Costa L, Fonseca BM, Rebelo I. Dissimilar effects of curcumin on human granulosa cells: beyond its antioxidative role. Reprod Toxicol. 2020;95:51–8.

    CAS  PubMed  Google Scholar 

  354. Lucas CG, Remiao MH, Komninou ER, Domingues WB, Haa C, de Leon PMM, et al. Tretinoin-loaded lipid-core nanocapsules decrease reactive oxygen species levels and improve bovine embryonic development during in vitro oocyte maturation. Reprod Toxicol. 2015;58:131–9.

    CAS  PubMed  Google Scholar 

  355. Spinaci M, Volpe S, De-Ambrogi M, Tamanini C, Galeati G. Effects of epigallocatechin-3-gallate (EGCG) on in vitro maturation and fertilization of porcine oocytes. Theriogenology. 2008;69:877–85.

    CAS  PubMed  Google Scholar 

  356. Hao J, Tuck AR, Sjodin MOD, Lindberg J, Sand A, Niklasson B, et al. Resveratrol supports and alpha-naphthoflavone disrupts growth of human ovarian follicles in an in vitro tissue culture model. Toxicol Appl Pharmacol. 2018;338:73–82.

    CAS  PubMed  Google Scholar 

  357. Wu M, Ma L, Xue L, Ye W, Lu Z, Li X, et al. Resveratrol alleviates chemotherapy-induced oogonial stem cell apoptosis and ovarian aging in mice. Aging. 2019;11.

  358. Capcarova M, Petruska P, Zbynovska K, Kolesarova A, Sirotkin AV. Changes in antioxidant status of porcine ovarian granulose cells after quercetin and T-2 toxin treatment. J Environ Sci Health B. 2015;50:201–6.

    CAS  PubMed  Google Scholar 

  359. Amoura M, Abou-El-Naga. The role of curcumin to ameliorate the toxic effect of benzo (A) pyrene on some organs of adult and newborn mice. Egypt J Exp Bio (Zool). 2006;2:61–72.

    Google Scholar 

  360. Yılmaz N, Seven B, Timur H, Yorganci A, Inal HA, Kalem MN, et al. Ginger (Zingiber officinale) might improve female fertility: a rat model. J Chin Med Assoc. 2018;81:905–11.

    PubMed  Google Scholar 

  361. Abolaji AO, Ojo M, Afolabi TT, Arowoogun MD, Nwawolor D, Farombi EO. Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Chemico-Biol Interac. 2017;270:15–23.

    CAS  Google Scholar 

  362. Hosseinzadeh H, Tafaghodi M, Mosavi MJ, Taghiabadi E. Effect of aqueous and ethanolic extracts of Nigella sativa seeds on milk production in rats. J Acupunct Meridian Stud. 2013;6:18–23.

    PubMed  Google Scholar 

  363. Goka MSC, Awouafack MD, Lamshoft M, Lienou LL, Mbemya GT, Fekam FB, et al. Comparative effect of the aqueous extracts of Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis on the sexual maturation of pregnant mare serum gonadotrophin-primed immature female rats. J Basic Clin Physiol Pharmacol. 2018;29:473–81.

    CAS  PubMed  Google Scholar 

  364. Sandeep PM, Bovee TFH, Sreejith K. Anti-androgenic activity of Nardostachys jatamansi DC and Tribulus terrestris L. and their beneficial effects on polycystic ovary syndrome–induced rat model. Metab Syndr Relat Disord. 2015;13:248–54.

    CAS  PubMed  Google Scholar 

  365. Jha U, Asad M, Asdaq SMB, Das AK, Prasad VS. Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats. J Ethnopharmacol. 2010;127:561–4.

    PubMed  Google Scholar 

  366. Liang J, Hou HY, Sun Y, Chen YQ. Protective effect of Schisandra extract on embryotoxicity and reproductive toxicity in early pregnant rats exposed to benzo [a] pyrene. Chinese J Integ Tradi Western Medi. 2016;36:234–8.

    Google Scholar 

  367. Ilhan M, Ali Z, Khan IA, Tastan H, Akkol EK. Promising activity of Anthemis austriaca Jacq. on the endometriosis rat model and isolation of its active constituents. Saudi Pharm J. 2019;27:889–99.

    PubMed  PubMed Central  Google Scholar 

  368. Ilhan M, Ali Z, Khan IA, Tastan H, Akkol EK. The regression of endometriosis with glycosylated flavonoids isolated from Melilotus officinalis (L.) Pall. in an endometriosis rat model. Taiwan J Obstet Gynecol. 2020;59:211–9.

    PubMed  Google Scholar 

  369. Farzana F, Sulaiman A, Ruckmani A, Vijayalakshmi K, Karunya Lakshmi G, Shri RS. Effects of flax seeds supplementation in polycystic ovarian syndrome. J Res Med Sci. 2015;31(1):113–9.

    Google Scholar 

  370. Canning S, Waterman M, Orsi N, Ayres J, Simpson N, Dye L. The efficacy of Hypericum perforatum (St John’s wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS Drugs. 2010;24(3):207–25.

    PubMed  Google Scholar 

  371. Agha-Hosseini M, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomized and placebo-controlled trial. BJOG. 2008;115(4):515–9.

    CAS  PubMed  Google Scholar 

  372. Najafipour F, Rahimi AO, Mobaseri M, Agamohamadzadeh N, Nikoo A, Aliasgharzadeh A. Therapeutic effects of stinging nettle (Urtica dioica) in women with hyperandrogenism. Int J Curr Res Aca Rev. 2014;2(7):153–60.

    CAS  Google Scholar 

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The authors acknowledge the financial support provided by CSIR (Council of Scientific and Industrial Research), New Delhi and UGC-SAP, New Delhi.

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Bhardwaj, J.K., Panchal, H. & Saraf, P. Ameliorating Effects of Natural Antioxidant Compounds on Female Infertility: a Review. Reprod. Sci. 28, 1227–1256 (2021). https://doi.org/10.1007/s43032-020-00312-5

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