Reproductive Health

Caring for your fertility health is key to starting or growing your family

Fertility is your ability to produce a child, therefore, looking after fertility health is highly important for both men and women when conceiving. There are many factors involved in achieving a successful pregnancy, including the production of healthy sperm and eggs, a healthy embryo and a healthy womb. Creating life is a complex biological event, and is commonly described as a ‘miracle’.

Many factors can affect fertility health including poor nutrition, age, weight, toxins (e.g. alcohol, smoking, drugs, pollution), stress or even high caffeine intake. These factors can reduce the chances of getting pregnant, but in more serious cases can cause infertility (inability to bear children) amongst couples. As defined by the World Health Organization (WHO), infertility is when a couple is unable to fall pregnant after 12 months of trying to conceive.

OVU-FORT® and SPER-FORT® are formulations designed specifically to support women’s and men’s reproductive health, respectively. Suited for individuals who are planning to conceive, it is recommended that adults take these formulations 3 months prior to conception. Find out how OVU-FORT® and SPER-FORT® can help you on your journey of starting or growing your family in this article.

Conception – How Life Begins

The beginning of creating a baby starts with conception, when a male sperm fertilises a female egg successfully. The chances of an egg being fertilised by a sperm are many millions to one.

After a couple engages in sexual intercourse, semen is deposited at the neck of a women’s uterus and sperm start the journey of fertilising the egg. Fertilisation needs to be completed within 48 hours, before the sperm die. Therefore, once in the female reproductive system, sperm increase their motility to reach the egg quicker. Millions of sperm travel through the womb to reach the Fallopian tube. Up to 1000 sperm surround the egg and try to penetrate it, but only one can do this successfully. As soon as a sperm penetrates the egg, a chemical reaction takes place in the egg’s cell membrane to prevent other sperm from entering. Fertilisation has been completed, and this fertilised egg is now called a zygote.

The zygote divides to form more cells, while it moves along the Fallopian tube. After 4 days the zygote has 100 cells and is called a blastocyst and it will move to implant itself on the uterine wall. The blastocyst secretes the hormone HCG, which is detected in pregnancy tests to confirm the wonderful news that the woman is pregnant. After nine months, the fetus has reached maturity and is ready to enter the world and begin life.

Challenges couples can encounter during conception

In Australia, statistics show that one in six couples experience fertility problems [1], making it a common health issue for couples. Due to the presence of both female and male factors, the causes of conception difficulties and infertility can be wide ranging. Below are some factors that can effect fertility for men and women:

Factors Effecting Female Fertility

In Australia, many women are having children at an older age [1]. A woman’s fertility starts to decline in her early thirties [2], hence, delaying motherhood can affect a woman’s chances of conceiving.

A woman is born with all the eggs she requires for a lifetime, and her eggs will decrease in quality and quantity as she ages [2]. This is the reason why age is the most important factor affecting a women’s fertility.

Other factors that can effect female fertility include problems with the reproductive system (e.g. ovary, fallopian tubes and uterus), hormone imbalances or immune system.

How OVU-FORT® supports female fertility health

Women are responsible for the majority of the reproductive process during pre-conception and fertilisation, OVU-FORT® is designed specifically to support female reproductive health. It provides nutrients important for pre-conception and early embryo development, helps manage irregular periods and overall general wellbeing.

Understanding how OVU-FORT® works

OVU-FORT® is a comprehensive women’s formulation with 15 active ingredients, including herbs (ashwagandha, chasteberry), antioxidants, nutrients (citrus bioflavonoids, inositol), vitamins and minerals. Here is evidence based information on how these active ingredients work to support female reproductive health.

Withania somnifera (Ashwagandha)

Is a herb that has been used in traditional medicine for gynecological conditions. Withania somnifera supplementation is likely to work similarly to estrogen during the first half of the month, where it is involved in oocyte maturation and endometrial growth. Pre-clinical scientific research suggested an increase in reproductive capacity and improved pregnancy outcome after short term administration of this herb [3, 4]. This herb also exerts stress relieving properties, clinical results demonstrated it reduced fatigue and improved alertness [5] which can help with the emotional journey of conceiving.

Vitex agnus-castus (Chasteberry)

Is a traditional herb of Mediterranean origin. It contains a range of compounds that exert similar effects as progesterone. In menstruating women, Vitex agnus-castus has been used to alleviate symptoms of PMS (e.g. cramps, breast pain and fluid retention). It can also help support endometrial growth during conception. In several clinical studies, formulations containing Vitex agnus-castus resulted in improved pregnancy and birth rates in women with progesterone-related cycle problems [6-9] or polycystic ovary syndrome (PCO/PCOS) [10].

Citrus bioflavonoids

A novel proprietary blend of citrus fruits derivatives that have antioxidant and anti-inflammatory activity. Found in citrus fruits, citrus bioflavonoids (e.g. hesperidin) are water soluble compounds. In a pre-clinical trial [11], results showed that the antioxidant activity of hesperidin protected ovaries from oxidative damage. In addition, hesperidin increased the number of maturing follicles and increased ovary weight [11].

B-vitamins: Pyridoxine (vitamin B6), Folic acid (vitamin B9) & Cyanocobalamin (vitamin B12)

B vitamins are essential for different metabolic processes in the body. Pyridoxine is required for the formation of red blood cells and influences brain processes and development, immune function and steroid hormone activity [12].

Folic acid is critical for the genetic control of the egg and early embryo. Higher folic acid intake is associated with improvments in implantation and birth rates in infertile women [12].

Cyanocobalamin functions include helping nerve function, mental ability and red blood cell formation.

Ascorbic acid (Vitamin C)

Vitamin C has antioxidant properties and other functions that include involvement in the metabolism of iron and folate [13]. Almost twice as much ascorbate is found in the fluid surrounding the eggs developing in the ovary [14]. Ascorbic acid supplementation (500mg) during the pre-conception stages resulted in improvement in pregnancy rates, and increases in follicular fluid levels of ascorbate [15]. Another trial in infertile women showed improved progesterone levels and pregnancy rates with ascorbic acid (750mg) supplementation [16].

Colecalciferol (Vitamin D)

Vitamin D is essential for healthy bones, muscles and overall health. It assists calcium absorption in the body, as well as being involved in other metabolic processes. Research indicates that vitamin D deficiency can contribute to infertility, suggesting it has an important role in reproduction [17]. In the ovary, activated vitamin D3 is involved in estrogen synthesis [17]. Vitamin D insufficiency has been linked to an increase risk of gestational diabetes mellitus [18] which is linked to insulin resistance and reduced fertility [19].

Inositol

An important sugar used for the production of phosphatidylinositol (PI) and myo-inositol, two important lipids that form signals to regulate sperm-egg interactions, early cell division in the embryo and implantation. Fallopian tube levels of myo-inositol have been found to correlate with oocyte quality [20]. Supplementation with inositol may assist with lack of mature oocytes and estrogen imbalances in some infertile women [21-22].

Alpha-tocopherol (Vitamin E)

Vitamin E is a lipid-soluble antioxidant. In combination with Vitamin C (also featured in OVU-FORT®) they function synergistically to prevent oxidative stress. In a scientific study, vitamin E correlated to improved estrogen production [23]. In a clinical study, supplementation of vitamin E (400IU) resulted in improved endometrial thickness due to its antioxidant effect, which may help implantation [24].

Essential minerals: Iron, Selenium, Zinc, Iodine, Magnesium

Each of these essential minerals are important for pre-conception. Iron is important for hemoglobin production and cardiovascular health [25]. Iron deficiency can result in ovulation problems, making it harder to conceive. The glycinate form of iron used in OVU-FORT®is ideal for women with gastrointestinal problems, because it is easily absorbed.

Selenium is important for healthy immune and thyroid gland function. It is also used in antioxidant production, which is important in the oocyte and early embryo.

Zinc is required to maintain the health of cells. In a clinical trial, zinc supplementation was associated with a reduction in pregnancy complications in zinc deficient women [26].

Iodine is required in our bodies for the production of essential thyroid hormones. The thyroid is a gland in the throat that is responsible for regulating many metabolic processes, such as growth and energy use [27]. Iodine deficiency can impair thyroid function and contribute to infertility [28-29].

Magnesium is required for many processes including stabilisation of DNA and RNA, energy production, muscle and nerve function. In a clinical trial, women were supplemented with a formulation containing magnesium and it was found to improve magnesium levels in the follicular fluid in women having fertility problems [30].

Factors Effecting Male Fertility

Infertility is a common problem, and in approximately one in five infertile couples the problem lies solely on the man [31].
Around two-thirds of infertile men have a sperm production problem, making this the most common cause of male infertility [31]. The sperm production problems are low sperm count (oligospermia) or the sperm produced does not function properly (e.g. asthenozoospermia, where sperm have reduced motility) [31]. Around 30-80% of infertility cases are caused by oxidative stress, and decreased level of seminal total antioxidant capacity which negatively affects sperm quality and function.

Age is a factor influencing men’s fertility, where fertility generally starts to decline after 40 due to a decrease in sperm quality [2]. Increasing male age reduces the overall chances of conception, increases time to pregnancy, or can lead to other pregnancy complications.

Sperm are male reproductive cells that are produced by the testes on a daily basis. Healthy and fully developed sperm are small in size (0.05mm long) and cannot be seen by the human eye. Sperm are specialised cells that are made up of three parts, a head, neck and tail. The head contains the male DNA (genetic material), its designed to bind to and then penetrate the egg. The tail contains the mitochondria which provides energy for the sperm to move. Sperm have a challenging journey through the female reproductive tract to reach the egg for fertilisation, hence, caring for sperm health is important for conception.

How SPER-FORT® supports male fertility health

SPER-FORT® is a formulation designed specifically for men to support healthy sperm production and quality, maintain reproductive health, and general well-being. SPER-FORT® provides the combined health benefits of antioxidants, herbs, vitamins and minerals.

SPER-FORT® works by targeting 3 key factors that affect sperm health:

  1. Antioxidant activity to reduce oxidative stress
  2. Supporting spermatogenesis, the maturation of sperm
  3. Supporting sperm metabolism

Understanding how SPER-FORT® works

SPER-FORT® is a male fertility formulation consisting of 11 active ingredients, including herbs (ashwagandha, stinging nettle), antioxidants (e.g. lycopene, vitamin c), nutrients, vitamins and minerals. Here is evidence based information on how these active ingredients work.

Withania somnifera (Ashwagandha)

An ayurvedic herb with antioxidant, anti-stress and aphrodisiac properties. In clinical studies, Ashwagandha improved overall sperm health and quality by reducing sperm death and oxidative stress, and improving semen quality, testosterone and antioxidant activity in healthy and infertile men [32-36]. In men with lower sperm counts, Withania improved sperm count (by 167%), motility (by 57%) and semen volume (by 53%) [33].

Urtica dioica (Stinging Nettle)

Stinging Nettle has been used in traditional medicine for its anti-oxidant and anti-inflammatory properties [37]. In a scientific study, Stinging Nettle administration inhibited nicotine-induced negative adverse effects on sperm (e.g. reduced viability, count, motility) and increased sperm health, count, motility and testosterone [37]. Another study found that it can provide symptomatic relief from prostate enlargement and urinary infections [38], which are often associated with loss of sperm quality.

Lycopene

A carotenoid that gives fruits and vegetables its red colour (e.g. tomatoes) and has antioxidant activity. It is found in high concentrations in the testes and semen, and protects sperm from oxidative stress. Decreased levels of lycopene in the testes and seminal plasma has been demonstrated in men with infertility due to low sperm motility and low sperm count. Clinical trials showed that lycopene supplementation improved sperm parameters, including count, motility and morphology, which contributed to improved pregnancy rates (36%) [39, 40].

L-carnitine

A nutrient required for sperm maturation and energy production, and accumulates in the testes. L-carnitine protects against oxidative stress. Men with infertility had lower levels of L-carnitine in the seminal fluid compared to fertile men [41]. Clinical trials found that maintaining L-carnitine levels in the seminal plasma is important for male fertility health, and supplementation of L-carnitine improved sperm motility in men affected by infertility, leading to increased pregnancy rates [41-42].

Zinc

An antioxidant and essential mineral that is required by all cells. Zinc is abundant in the testes and prostate where it is required for the production of new sperm (spermatogenesis). Men with asthenozoospermia was associated with low serum zinc levels, high oxidative stress, and low antioxidant capacity [43-47]. Zinc supplementation improved sperm parameters in men with asthenozoospermia by preventing oxidative stress, sperm cell death and sperm DNA fragmentation [43, 47].

Selenium

An essential mineral that supports key antioxidant enzymes (e.g. PHGpx, GPX) made by the testes and sperm, to protect sperm DNA, growth and maturation processes. PHGPx activity is higher in fertile men, and is associated with sperm viability and motility [48]. Selenium is also involved in testosterone production [49]. In combination with vitamins A, C and/or E, selenium helped reduce lipid oxidation in semen, improving sperm parameters and testosterone levels in infertile men [49-52].

Ascorbic acid (Vitamin C)

An antioxidant that is important for the body, and in the testes vitamin C protects sperm from lipid oxidation. Semen vitamin C levels are directly related to sperm health and quality, where low levels of vitamin C are related to low sperm count (oligospermic) and DNA damage [53-55]. Vitamin C supplementation improved sperm count, motility and morphology in oligospermic infertile men after two months [56], and sperm quality in men who were heavy smokers [57].

Alpha-tocopherol (Vitamin E)

A fat soluble vitamin, it has antioxidant activity that prevents lipid oxidation in cell membranes. Working with vitamin C, it helps protect new and mature sperm. Infertile men have lower serum and semen vitamin E levels compared to fertile men [58] which correlates to sperm quality. Vitamin E supplementation improved sperm parameters of oligospermia and asthenospermia in infertile men, including increased sperm concentration, motility and rate of natural pregnancy [59]. Supplementation also improved sperm-egg binding ability [59-62] and lowered sperm DNA damage [63].

B-vitamins: Pyridoxine (vitamin B6), Folic acid (vitamin B9) & Cyanocobalamin (vitamin B12)

B vitamins are essential for different metabolic processes in the body and support male reproductive health.

Folic acid is involved in DNA synthesis and methylation, processes that support sperm production, normality and testes health. Low folate levels in semen and blood are associated with low sperm count [64]. Folic acid supplementation improved sperm parameters in fertile and sub-fertile men, including increased sperm count, concentration, motility and morphology [65, 66].

Pyridoxine and cyanocobalamin are involved in energy production. Higher vitamin B6 levels correlated to lower sperm DNA damage [67], while low vitamin B12 levels in semen is associated with low sperm count and motility in men [68-69].

Summary

OVU-FORT® and SPER-FORT® are formulations designed to support female and male reproductive health, respectively.

OVU-FORT® provides nutrients important for pre-conception, helps manage irregular periods and general wellbeing in preparation for conceiving.

SPER-FORT® includes antioxidants and nutrients to supports healthy sperm production and quality, maintain reproductive health, and general well-being.

References

  1. http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert Accessed on 13/2/17.
  2. https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/age-and-fertility Access on 14/2/17.
  3. Riaz, A., et al., Assessment of acute toxicity and reproductive capability of a herbal combination. Pak J Pharm Sci, 2010. 23(3): p. 291-294.
  4. Sharma, S., S.A. Dahanukar, and S.M. Karandikar, Effects of long term administration of the roots of ashwagandha and shatavari in rats. 1985.
  5. Auddy, B., et al., A Standardized Withania Somnifera Extract Significantly Reduces Stress-Related Parameters in Chronically Stressed Humans: A Double-Blind, Randomized, Placebo-Controlled Study. Journal of the American Nutraceutical Association, 2008. 11(1): p. 50-56.
  6. Gerhard, I., et al., Mastodynon® bei weiblicher Sterilität. Forschende Komplementärmedizin/Research in Complementary Medicine, 1998. 5(6): p. 272-278.
  7. Bergmann, J., et al., [The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study]. Forsch Komplementarmed Klass Naturheilkd, 2000. 7(4): p. 190-9.
  8. Westphal, L.M., et al., A nutritional supplement for improving fertility in women. J Reprod Med, 2004. 49(4): p. 289-93.
  9. Westphal, L.M., M.L. Polan, and A.S. Trant, Double-blind, placebo-controlled study of Fertilityblend: a nutritional supplement for improving fertility in women. Clinical and experimental obstetrics & gynecology, 2005. 33(4): p. 205-208.
  10. Arentz, S., et al., Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism a review of the laboratory evidence for effects with corroborative clinical findings, in BMC Complement. Altern. Med. 2014.
  11. Khedr, N.F., Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries. Exp Biol Med (Maywood). 2015 Dec; 240(12): 1682–1689.
  12. https://www.betterhealth.vic.gov.au/health/healthyliving/vitamin-b Accessed on 15/2/17. Gaskins, J.A., et al., Dietary Folate and Reproductive Success Among Women Undergoing Assisted Reproduction. Obstetrics & Gynecology, 2014. 124(4): p. 801-809.
  13. http://www.who.int/elena/titles/vitaminsec-pregnancy/en/ Accessed on 15/2/17.
  14. Paszkowski, T. and R. Clarke, The Graafian Follicle Is a Site of L-Ascorbate Accumulation. Official Publication of ALPHA, Scientists in Reproductive Medicine, 1999. 16(1): p. 41-45.
  15. Crha, I., et al., Ascorbic acid and infertility treatment. Central European journal of public health, 2003. 11(2): p. 63-67.
  16. Henmi, H., et al., Effects of ascorbic acid supplementation on serum progesterone levels in patients with a luteal phase defect. Fertility and Sterility, 2003. 80(2): p. 459-461.
  17. Potashnik, G., et al., The relationship between endogenous oestradiol and vitamin D 3 metabolites in serum and follicular fluid during ovarian stimulation for in-vitro fertilization and embryo transfer. Human Reproduction, 1992. 7(10): p. 1357-1360. Dabrowski, F.A., Grzechocinska, B. and Wielogos, M. The Role of Vitamin D in Reproductive Health—A Trojan Horse or the Golden Fleece? Nutrients. 2015 Jun; 7(6): 4139–4153.
  18. Bodnar, L.M., et al., Maternal vitamin D deficiency increases the risk of preeclampsia. The Journal of clinical endocrinology and metabolism, 2007. 92(9): p. 3517.
  19. Anderson, K., V. Nisenblat, and R. Norman, Lifestyle factors in people seeking infertility treatment – A review, in Aust. N. Z. J. Obstet. Gynaecol. 2010. p. 8-20.
  20. Chiu, T.T.Y., et al., Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Human Reproduction, 2002. 17(6): p. 1591-1596.
  21. Brusco, G.F. and M. Mariani, Inositol: effects on oocyte quality in patients undergoing ICSI. An open study.
  22. Papaleo, E., et al., Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertility and Sterility, 2009. 91(5): p. 1750-1754.
  23. Cigliano, L., et al., Lecithin-cholesterol acyltransferase activity during maturation of human preovulatory follicles with different concentrations of ascorbate, -tocopherol and nitrotyrosine. Reproduction, Fertility and Development, 2002. 14(1-2): p. 15-21.
  24. Cicek, N., et al., Vitamin E effect on controlled ovarian stimulation of unexplained infertile women. Official Publication of ALPHA, Scientists in Reproductive Medicine, 2012. 29(4): p. 325-328.
  25. https://www.betterhealth.vic.gov.au/health/healthyliving/nutrition-womens-extra-needs Accessed on 15/2/17.
  26. Nossier, S.A., et al., The effect of zinc supplementation on pregnancy outcomes: a double-blind, randomised controlled trial, Egypt. Br J Nutr, 2015. 114(2): p. 274-85.
  27. https://www.betterhealth.vic.gov.au/health/healthyliving/iodine Accessed on 16/2/17.
  28. Nossier, S.A., et al., The effect of zinc supplementation on pregnancy outcomes: a double-blind, randomised controlled trial, Egypt. Br J Nutr, 2015. 114(2): p. 274-85.
  29. Prummel, M.F. and W.M. Wiersinga, Thyroid autoimmunity and miscarriage. Eur J Endocrinol, 2004. 150(6): p. 751-5.
  30. Ozkaya, M.O., et al., Effects of multivitamin/mineral supplementation on trace element levels in serum and follicular fluid of women undergoing in vitro fertilization (IVF). Biol Trace Elem Res, 2011. 139(1): p. 1-9.
  31. https://www.andrologyaustralia.org/wp-content/uploads/Male-Infertility-Guide-WEB.pdf Accessed 16/2/17. Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: An evidence based review. Int J Reprod Biomed (Yazd). 2016 Dec;14(12):729-736.
  32. Ahmad, M.K., et al., Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril, 2010. 94(3): p. 989-96.
  33. Ambiye, V.R., et al., Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. Evid Based Complement Alternat Med, 2013. 2013: p. 571420.
  34. Gupta, A., et al., Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz. J Ethnopharmacol, 2013. 149(1): p. 208-14.
  35. Mahdi, A.A., et al., Withania somnifera Improves Semen Quality in Stress-Related Male Fertility. Evid Based Complement Alternat Med, 2009.
  36. Shukla, K.K., et al., Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations. Reprod Biomed Online, 2011.
  37. Jalili, C., M.R. Salahshoor, and A. Naseri, Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice. Iran J Reprod Med, 2014. 12(6): p. 401-8.
  38. Safarinejad, M.R., Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study. J Herb Pharmacother, 2005. 5(4): p. 1-11.
  39. Gupta, N.P. and R. Kumar, Lycopene therapy in idiopathic male infertility–a preliminary report. Int Urol Nephrol, 2002. 34(3): p. 369-72.
  40. Mohanty, N.K., et al., Management of idiopathic oligoasthenospermia with lycopene. Indian J Urol, 2001. 18: p. 57-61.
  41. Ahmed, S.D., et al., Role of L-carnitine in male infertility. J Pak Med Assoc, 2011. 61(8): p. 732-6.
  42. Zhou, X., F. Liu, and S. Zhai, Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr, 2007. 16 Suppl 1: p. 383-90.
  43. Omu, A.E., et al., Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Med Princ Pract, 2008. 17(2): p. 108-16.
  44. Yuyan, L., et al., Are serum zinc and copper levels related to semen quality? Fertil Steril, 2008. 89(4): p. 1008-11.
  45. Hunt, C.D., et al., Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men. Am J Clin Nutr, 1992. 56(1): p. 148-57.
  46. Deng, C.H., B. Zheng, and S.F. She, [A clinical study of biological zinc for the treatment of male infertility with chronic prostatitis]. Zhonghua Nan Ke Xue, 2005. 11(2): p. 127-9.
  47. Omu, A.E., H. Dashti, and S. Al-Othman, Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol, 1998. 79(2): p. 179-84.
  48. Foresta, C., et al., Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod, 2002. 67(3): p. 967-71.
  49. Safarinejad, M.R. and S. Safarinejad, Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol, 2009. 181(2): p. 741-51.
  50. Keskes-Ammar, L., et al., Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl, 2003. 49(2): p. 83-94.
  51. Scott, R., et al., The effect of oral selenium supplementation on human sperm motility. Br J Urol, 1998. 82(1): p. 76-80.
  52. Vezina, D., et al., Selenium-vitamin E supplementation in infertile men. Effects on semen parameters and micronutrient levels and distribution. Biol Trace Elem Res, 1996. 53(1-3): p. 65-83.
  53. Thiele, J.J., et al., Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washed semen. Hum Reprod, 1995. 10(1): p. 110-5.
  54. Song, G.J., E.P. Norkus, and V. Lewis, Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men. Int J Androl, 2006. 29(6): p. 569-75.
  55. Ebesunun, M.O., et al., Plasma and semen ascorbic levels in spermatogenesis. West Afr J Med, 2004. 23(4): p. 290-3.
  56. Akmal, M., et al., Improvement in human semen quality after oral supplementation of vitamin C. J Med Food, 2006. 9(3): p. 440-2.
  57. Dawson, E.B., et al., Effect of ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril, 1992. 58(5): p. 1034-9.
  58. Benedetti, S., et al., Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod Biomed Online, 2012. 25(3): p. 300-6.
  59. Chen, X.F., et al., [Efficacy of natural vitamin E on oligospermia and asthenospermia: a prospective multi-centered randomized controlled study of 106 cases]. Zhonghua Nan Ke Xue, 2012. 18(5): p. 428-31.
  60. Geva, E., et al., The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program. Fertil Steril, 1996. 66(3): p. 430-4.
  61. Kessopoulou, E., et al., A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertil Steril, 1995. 64(4): p. 825-31.
  62. Suleiman, S.A., et al., Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl, 1996. 17(5): p. 530-7.
  63. Greco, E., et al., Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl, 2005. 26(3): p. 349-53.
  64. Wallock, L.M., et al., Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Fertil Steril, 2001. 75(2): p. 252-9.
  65. Wong, W.Y., et al., Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril, 2002. 77(3): p. 491-8.
  66. Bentivoglio, G., F. Melica, and P. Cristoforoni, Folinic acid in the treatment of human male infertility. Fertil Steril, 1993. 60(4): p. 698-701.
  67. Vujkovic, M., et al., Associations between dietary patterns and semen quality in men undergoing IVF/ICSI treatment. Hum Reprod, 2009. 24(6): p. 1304-12.
  68. Crha, I., et al., Seminal plasma homocysteine, folate and cobalamin in men with obstructive and non-obstructive azoospermia. J Assist Reprod Genet, 2010. 27(9-10): p. 533-8.
  69. Boxmeer, J.C., et al., Seminal plasma cobalamin significantly correlates with sperm concentration in men undergoing IVF or ICSI procedures. J Androl, 2007. 28(4): p. 521-7.