Antioxidants Like Melatonin and CoQ10 May Help Mitigate the Impact of Environmental Exposures and Aging on Reproductive Health.
We live in an increasingly toxic world, with literally thousands of different potential toxins being released into our water, air, and soil each day by industry, agricultural practices, and our daily living.,,, These toxins cycle into our food supply, accumulating in animals and plants.,,, Many environmental pollutants do not degrade over time, and thus continue to accumulate; these chemicals are classified as persistent organic pollutants. Pollutants such as these also don’t remain in one place—they are cycled in our environment and distributed globally.,
Environmental toxicants impact our longevity, increase our risk for chronic disease, and gravely affect our reproductive health as well.,,, Exposure to toxic pollutants is not only a reproductive factor in our older years – it also has an impact when we are young.,,, Because females have a limited amount of gametes, set from the moment they are born, and their detoxification surfaces and pathways have a lower capacity then men, the long-term impact of toxicants on female fertility may be more dramatic. Other factors such as immune dysfunction and autoimmunity also disproportionately affect females and may be environmentally triggered factors in female infertility.
The two key ways in which environmental toxins adversely affect our health is by their endocrine effects and the oxidative damage they cause. In addition to limiting exposure to toxins, undertaking a comprehensive assessment of exposure and using evidence-based supplements and medications to safely remove them is paramount, particularly if historic exposures are significant.
Herein, we take a look at the different antioxidant therapies that have been clinically studied and shown to be of benefit for reproductive health in both males and females struggling with infertility, highlighting melatonin and coenzyme Q10 (CoQ10).
It may come as a surprise that the hormone/antioxidant best known for the role it plays in our sleep cycle has also been studied for its reproductive impact. Extensive research exists on the anti-inflammatory and immune-regulating properties of melatonin, which may also give rise to its positive impact on both female and male reproductive health.,
The study of melatonin’s impact on female fertility largely grew out of research in the late ’80s that found high levels of melatonin in female preovulatory follicular fluid—approximately 3.5 times higher than the corresponding serum concentration. Animal and human studies suggest that the melatonin found in the follicular fluid is taken up the ovaries from systemic circulation, although some may also be produced in the ovaries themselves.In women, daily administration of 3 mg of melatonin in the evening has been shown to increase follicular levels of melatonin more than three-fold. Melatonin has been shown to impact follicular growth, with significantly higher levels of endogenous melatonin being found in the larger, healthier follicles versus the small follicles that were obtained from women for fertilization procedures.
The majority of research concerning melatonin for female fertility is in women undergoing in vitro fertilization (IVF)-embryo transfer (ET) procedures, using their own harvested oocytes. Supplementation with 3 mg of melatonin/day was found to lead to a higher percentage of mature oocytes being retrieved for IVF-ET procedure, with trends to a higher clinical pregnancy rate compared to placebo. In another study, melatonin taken at 3 mg/day was shown to significantly improve fertilization rates in women who failed to become pregnant in their last IVF-ET procedure. In a third clinical study of women undergoing IVF, the addition of 3 mg of melatonin to daily treatment with 200 mg of folic acid [CD1] and 2 g of myo-inositol significantly increased the number of mature oocytes, with trends toward higher implantation and clinical pregnancy rates. Multiple additional human studies also point to similar effects on oocyte quality and fertilization rates.,,,
The effects of melatonin on female reproductive health are not limited to those undergoing IVF treatment, of course—the potential benefits of this antioxidant/hormone also extend to several other conditions that affect the female reproductive system. Numerous cellular and animal studies suggest melatonin may have a positive impact on endometriosis; recurrent spontaneous abortion; PCOS; and immune-, chemotherapy-, or radiation-induced primary ovarian insufficiency; as well as the normal fertility decline with aging.,
The data suggests that supplemental melatonin may also have a positive impact on male reproductive health. Men who are fertile tend to have higher blood and semen melatonin levels, on average, than those who are infertile., In men being counseled for infertility, higher (endogenous) urinary melatonin metabolite (6-sulfatoxymelatonin [aMT6s]) levels were significantly and positively associated with sperm concentration, forward motility, and normal morphology range. Significantly lower testicular melatonin levels have also been shown to be associated with testicular histological abnormalities. A comparison of morning urinary aMT6s levels between infertile males and recent fathers showed significantly higher levels in the new fathers, despite both groups being individuals who worked night shifts.38
Although seminal plasma melatonin levels are significantly lower than those of the blood, melatonin administration still dramatically increases both seminal plasma and serum levels, similar to its effects in women. The addition of melatonin to semen in vitro improves sperm viability, motility, penetration ability, and subsequent embryo development.,, Studies both in vitro and in humans have also shown that melatonin protects sperm from oxidative stress and DNA fragmentation,—which is important not only for conception, but also for the growth and development of the fetus into a healthy child.
Oral melatonin supplementation has been shown to increase melatonin levels in human testes, where sperm are produced, and to decrease oxidative stress and inflammation-related markers. In a population of infertile men having idiopathic azoospermia, melatonin, taken at a dose of 3 mg for three months, significantly lowered the number of testicular macrophages and improved histological abnormalities, specifically decreasing testicle tubular wall fibrosis. Initially, testicular macrophage numbers and tubule wall thickness in the men with histological abnormalities were approximately double those of the men without such abnormalities; with melatonin supplementation, the macrophage levels and tubule wall thickness were nearly restored to those of the men with normal histology.
Melatonin also protects sperm against the damage caused by environmental pollutants, including BPA, heavy metals (cadmium, mercury, and lead),,, and pesticides (diazinon and others)., Melatonin receptors exist in numerous cell types associated with male reproductive function—Leydig cells, Sertoli cells, and several different testicular immune cells—shedding light on a wide array of potential reproductive functions.Although further studies are needed, the evidence points to melatonin as a supplement that can ameliorate oxidative stress and perhaps improve male fertility.
In similar ways, CoQ10 also helps protect the gametes. Like melatonin, CoQ10 is a fat-soluble antioxidant and helps protect cellular membranes from oxidative stress. Additionally, CoQ10 is an important nutrient for mitochondrial energy production—a factor for both male and female reproductive health. Because CoQ10 levels decline with aging, it is perhaps not a surprise that a primary focus of research with this nutrient concerns diseases and conditions associated with aging: cardiovascular and metabolic disease, neurodegenerative disorders, sarcopenia and muscle strength, skin changes such as wrinkles, and “reproductive aging,” the term used to describe nonspecific fertility decline with age.
A female factor in reproductive aging is the dwindling supply of viable oocytes. One factor in oocyte viability is its ability to mature, which was touched on lightly in the discussion of melatonin. Prior to its release from the ovary, an oocyte undergoes a complex and energy-intensive process of nuclear, cytoplasmic, and even epigenetic changes that allow it to mature to a “ripe” stage where it is ready to be fertilized. Then, during the process of its release from the ovary, it also is subject to increased oxidative stress, which, in a not-so-healthy oocyte, can lead to membrane and organelle damage, making it not compatible with fertilization.
Clearly, antioxidants are an important tool as they promote healthy oocyte maturation and help protect the oocyte from this oxidative damage. Additionally, alterations in mitochondrial energy production are factors contributing to the decline in maturation of viable oocytes with age. Enter stage left: CoQ10.
The primary energy-generating pathway in the developing oocyte is mitochondrial oxidative phosphorylation, which depends on adequate amounts of CoQ10. The steps involved in energy production also generate substantial oxidative stress and can be very damaging to the mitochondria, giving further rise to this antioxidant’s local importance.
In an aged animal model, dietary supplementation with CoQ10 was shown to significantly increase the number of ovulated eggs, while other mitochondrial nutrients (lipoic acid and resveratrol) were not observed to have such an effect. In further studies of female mice with compromised antioxidant defense pathways, supplementation with CoQ10 was also shown to greatly ameliorate the related decline in fertility. In cellular studies, CoQ10 has also specifically been shown to help protect germ cells (a precursor to gametes) against damage due to exposure to BPA.
Clinical studies with CoQ10 have also shown promising results. In one of these studies, women under the age of 35 shown to have diminished ovarian reserve were randomized to receive placebo or 200 mg of CoQ10 three times daily for 60 days prior to IVF-ET treatment. In women taking CoQ10, significant improvements were seen in the number of retrieved oocytes, the quality of embryos, and the fertilization rate. While the ET procedure was canceled due to poor quality in 22.89% of women receiving the placebo, it was only canceled in 8.33% of those taking CoQ10. Clinical pregnancy and live birth rates after ET both tended to be higher in women given CoQ10, but the difference was not significant.
Lower rates of aneuploidy (an abnormal chromosome number, which may be incompatible with life or lead to genetic disorders) have also been seen with daily supplementation of 600 mg of CoQ10 in women undergoing IVF procedures; however, due to concerns of safety with the evaluation aspect of this study design, it was terminated prior to obtaining adequate data for this improvement to reach statistical significance.
CoQ10 has also been shown to improve multiple aspects of fertility in women with PCOS, a condition associated with anovulation and fertility struggles. Treatment with clomiphene citrate is the first-line therapy to induce ovulation in these women; however, it often remains unsuccessful, leading to studies of numerous nutraceuticals and pharmaceuticals as adjunctive therapies to improve outcomes. With PCOS, N-acetylcysteine may also be of benefit, and it has been the topic of multiple studies for the fertility and metabolic challenges this population faces.,
In a study of women with PCOS for whom treatment with clomiphene citrate was unsuccessful for multiple menstrual cycles, CoQ10 was considered as an adjunctive therapy. Women were randomized to receive clomiphene citrate alone, or with the addition of CoQ10 at a dose of only 60 mg three times daily from the beginning of their cycle to ovulation induction. The impact CoQ10 had on fertility was quite profound: there was a significant increase in number of larger mature follicles, endometrial thickness, ovulation rate (65.9 versus 15.5%), and clinical pregnancy rate (37.3 versus only 6%).
Clearly, the positive findings of the clinical and preclinical studies suggest CoQ10 may be of great benefit for women with diminished fertility due to a variety of causes, including the general decline with aging. However, an important point was brought up in a comprehensive review of the studies considering the impact CoQ10 has on reproductive aging. The point made was that many of the anti-aging fertility benefits seen in mouse models are with dietary supplementation of CoQ10 for a period that would be equivalent to a decade in human years, suggesting this antioxidant should be part of the daily protocol for any woman who wishes to consider childbirth in her later years.
In infertile men, CoQ10 has been extensively studied, primarily with regards to sperm counts and motility. CoQ10 also helps protect the cellular lipid membranes of sperm against oxidative stress, keeping them viable through the many stages of their journey to successful fertilization.
Sperm must swim long distances through viscous fluids of the female reproductive tract, and upon reaching the egg, encounter oxidative stress in the transition to a hyperactivated sperm and the process of fusing with the egg. Although the seminal plasma serves as a pH and general buffer for the dissimilar fluids of the vaginal tract, the journey still poses challenges. Excessive lipid peroxidation of spermatozoa cellular membranes can be a factor in infertility and make sperm less likely to achieve the mission at hand, giving rise to the importance of fat-soluble antioxidants like CoQ10.
Although oxidative stress is necessary and important for the final stages of fertilization, when it is out of balance with protective antioxidant factors, infertility can result. Crucially important for sperm motility and successful fertilization is mitochondrial function and energy production. Mitochondrial function also plays a major role in sperm penetration ability, a male fertility factor that will not be identified with standard sperm count assessments.
Semen CoQ10 concentrations have been shown to be significantly correlated with sperm numbers and motility., When lackluster human sperm are bathed in a CoQ10-enriched medium, their swimming ability has been shown to improve., Similar results have also been seen in otherwise healthy men with infertility due to decreased sperm counts and motility. In this population, supplementation of 150 mg of CoQ10 for six months significantly increased total sperm counts by 53%, sperm motility by 26%, and quantity of rapidly motile sperm by 41%. In another study of a similar population of men, CoQ10 supplementation at 200 or 400 mg per day for three months was shown to improve sperm concentration and motility, with slightly greater improvements at the higher dose.
These studies are not the only ones. A 2013 systemic review and meta-analysis of three randomized, double-blind, placebo-controlled trials found that supplementation of 200 to 300 mg of CoQ10/day for 12 to 26 weeks significantly increased sperm concentration and motility, along with an increase in seminal CoQ10 levels. Additional clinical trials subsequent to the 2013 review also found that supplemental CoQ10 (200 to 600 mg daily for three to six months) increased semen CoQ10 levels and improved sperm quality., Perhaps the most important finding from the study in which CoQ10 was taken at 600 mg a day was that 34% of the men (who all previously had a history of two years of failed attempts at conception) achieved successful pregnancy with their partners after a mean of 8.4 months.
While not discussed at length here, vitamins A, C, and E; lycopene; quercetin; and glutathione are additional antioxidants that have data from cellular and animal models showing that they may help protect against the detrimental effects environmental toxins have on reproductive health. Molecular hydrogen[CD2] is at an early stage in its research, and also shows promise for enhancing fertility via reduction of oxidative damage due to a variety of external and internal causes.,,,
 Soto AM, Sonnenschein C. Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol. 2010 Jul;6(7):363-70.
 Lelieveld J, et al. The contribution of outdoor air pollution sources to premature mortality on a global scale. Nature. 2015 Sep 17;525(7569):367-71.
 Klecka G, et al. Chemicals of emerging concern in the Great Lakes Basin: an analysis of environmental exposures. Rev Environ Contam Toxicol. 2010;207:1-93.
 Manzetti S, et al. Chemical properties, environmental fate, and degradation of seven classes of pollutants. Chem Res Toxicol. 2014 May 19;27(5):713-37.
 Sabir SM, et al. Effect of environmental pollution on quality of meat in district Bagh, Azad Kashmir. Pakistan J Nutr. 2003;2(2):98-101.
 Poliakova OV, et al. Accumulation of persistent organic pollutants in the food chain of Lake Baikal. Toxicol & Enviro Chem. 2000 Apr 1;75(3-4):235-43.
 Benavides MP, et al. Cadmium toxicity in plants. Brazil J Plant Physiol. 2005 Mar;17(1):21-34.
 de Geus HJ, et al. Environmental occurrence, analysis, and toxicology of toxaphene compounds. Environ Health Perspect. 1999 Feb;107 Suppl 1(Suppl 1):115-44.
 Wania F, Mackay D. Peer reviewed: tracking the distribution of persistent organic pollutants. Environ Sci Technol. 1996 Aug 27;30(9):390A-6A.
 Lovett GM, et al. Effects of air pollution on ecosystems and biological diversity in the eastern United States. United States. Ann N Y Acad Sci. 2009 Apr;1162(1):99-135.
 Carpenter DO. Environmental contaminants as risk factors for developing diabetes. Rev Environ Health. 2008 Jan-Mar;23(1):59-74.
 Irigaray P, et al. Lifestyle-related factors and environmental agents causing cancer: an overview. Biomed Pharmacother. 2007 Dec;61(10):640-58.
 Bhatnagar A, et al. Environmental cardiology: studying mechanistic links between pollution and heart disease. Circ Res. 2006 Sep 29;99(7):692-705.
 Mendiola J, et al. Exposure to environmental toxins in males seeking infertility treatment: a case-controlled study. Reprod Biomed Online. 2008 Jun;16(6):842-50.
 Selevan SG, et al. Semen quality and reproductive health of young Czech men exposed to seasonal air pollution. Environ Health Perspect. 2000 Sep;108(9):887-94.
 Rubes J, et al. Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality. Hum Reprod. 2005 Oct;20(10):2776-83.
 Perry MJ, et al. A prospective study of serum DDT and progesterone and estrogen levels across the menstrual cycle in nulliparous women of reproductive age. Am J Epidemiol. 2006 Dec 1;164(11):1056-64.
 Windham GC, et al. Exposure to organochlorine compounds and effects on ovarian function. Epidemiology. 2005 Mar;16(2):182-90.
 Butter ME. Are women more vulnerable to environmental pollution? J Human Ecol. 2006 Nov 1;20(3):221-6.
 Mendola P, et al. Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult female. Fertil Steril. 2008 Feb;89(2 Suppl):e81-94.
 Allergy Research Group. Melatonin, Immune Function, and Respiratory Health. FOCUS Newsletter. Fall 2020 Special Immunity Issue:14-8.
 Frungieri MB, et al. Local Actions of Melatonin in Somatic Cells of the Testis. Int J Mol Sci. 2017 May 31;18(6):1170.
 Tamura H, et al. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril. 2009 Jul;92(1):328-43.
 Brzezinski A, et al. Melatonin in human preovulatory follicular fluid. J Clin Endocrinol Metab. 1987 Apr;64(4):865-7.
 Tamura H, et al. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 2008 Apr;44(3):280-7.
 Nakamura Y, et al. Increased endogenous level of melatonin in preovulatory human follicles does not directly influence progesterone production. Fertil Steril. 2003 Oct;80(4):1012-6.
 Batıoğlu AS, et al. The efficacy of melatonin administration on oocyte quality. Gynecol Endocrinol. 2012 Feb;28(2):91-3.
 Rizzo P, et al. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci. 2010 Jun;14(6):555-61.
 Pacchiarotti A, et al. Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol. 2016;32(1):69-73.
 Nishihara T, et al. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014 May;30(5):359-62.
 Eryilmaz OG, et al. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J Assist Reprod Genet. 2011 Sep;28(9):815-20.
 Unfer V, et al. Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol. 2011 Nov;27(11):857-61.
 Yang HL, et al. Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome. Am J Reprod Immunol. 2018 Jul;80(1):e12839.
 Tamura H, et al. Long-term melatonin treatment delays ovarian aging. J Pineal Res. 2017 Mar;62(2).
 Zhang L, et al. Melatonin regulates the activities of ovary and delays the fertility decline in female animals via MT1/AMPK pathway. J Pineal Res. 2019 Apr;66(3):e12550.
 Chen HG, et al. Sleep duration and quality in relation to semen quality in healthy men screened as potential sperm donors. Environ Int. 2020 Feb;135:105368.
 Awad H, et al. Melatonin hormone profile in infertile males. Int J Androl. 2006 Jun;29(3):409-13.
 Ortiz A, et al. High endogenous melatonin concentrations enhance sperm quality and short-term in vitro exposure to melatonin improves aspects of sperm motility. J Pineal Res. 2011 Mar;50(2):132-9.
 Riviere E, et al. Melatonin daily oral supplementation attenuates inflammation and oxidative stress in testes of men with altered spermatogenesis of unknown aetiology. Mol Cell Endocrinol. 2020 Sep 15;515:110889.
 Luboshitzky R, et al. Seminal plasma melatonin and gonadal steroids concentrations in normal men. Arch Androl. 2002 May-Jun;48(3):225-32.
 Luboshitzky R, et al. Melatonin administration alters semen quality in healthy men. J Androl. 2002 Jul-Aug;23(4):572-8.
 Monllor F, et al. Melatonin diminishes oxidative damage in sperm cells, improving assisted reproductive techniques. Turk J Biol. 2017 Dec 18;41(6):881-9.
 Zhang XY, et al. Melatonin rescues impaired penetration ability of human spermatozoa induced by mitochondrial dysfunction. Reproduction. 2019 Nov;158(5):465-75.
 Pang YW, et al. Protective effects of melatonin on bovine sperm characteristics and subsequent in vitro embryo development. Mol Reprod Dev. 2016 Nov;83(11):993-1002.
 Espino J, et al. Melatonin as a potential tool against oxidative damage and apoptosis in ejaculated human spermatozoa. Fertil Steril. 2010 Oct;94(5):1915-7.
 Bejarano I, et al. Exogenous melatonin supplementation prevents oxidative stress‐evoked DNA damage in human spermatozoa. J Pineal Res. 2014 Oct;57(3):333-9.
 Othman AI, et al. Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity. Toxicol Ind Health. 2016 Sep;32(9):1537-49.
 Li R, et al. The protective effects of melatonin against oxidative stress and inflammation induced by acute cadmium exposure in mice testis. Biol Trace Elem Res. 2016 Mar;170(1):152-64.
 Romero A, et al. A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res. 2014 May;56(4):343-70.
 Olayaki LA, et al. Melatonin prevents and ameliorates lead-induced gonadotoxicity through antioxidative and hormonal mechanisms. Toxicol Ind Health. 2018 Sep;34(9):596-608.
 Sarabia L, et al. Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on mouse sperm DNA. Ecotoxicol Environ Safety. 2009 Feb 1;72(2):663-8.
 Osghari MH, et al. A review of the protective effect of melatonin in pesticide-induced toxicity. Expert Opin Drug Metab Toxicol. 2017 May;13(5):545-54.
 Díaz-Casado ME, et al. The Paradox of Coenzyme Q10 in Aging. Nutrients. 2019 Sep 14;11(9):2221.
 Hernández-Camacho JD, et al. Coenzyme Q10 Supplementation in Aging and Disease. Front Physiol. 2018 Feb 5;9:44.
 Fischer A, et al. Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts. PLoS One. 2016 Dec 1;11(12):e0167124.
 Žmitek K, et al. The effect of dietary intake of coenzyme Q10 on skin parameters and condition: Results of a randomised, placebo-controlled, double-blind study. Biofactors. 2017 Jan 2;43(1):132-40.
 Thibault C, et al. Mammalian oocyte maturation. Reprod Nutr Dev. 1987;27(5):865-96.
 Miyamoto K, et al. Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria. Free Radic Biol Med. 2010 Aug 15;49(4):674-81.
 Roth Z. Symposium review: Reduction in oocyte developmental competence by stress is associated with alterations in mitochondrial function. J Dairy Sci. 2018 Apr;101(4):3642-54.
 Bentov Y, Casper RF. The aging oocyte–can mitochondrial function be improved? Fertil Steril. 2013 Jan;99(1):18-22.
 Burstein E, et al. Co-enzyme Q10 supplementation improves ovarian response and mitochondrial function in aged mice. Fertil Steril. 2009 Sep 1;92(3):S31.
 Ishii N, et al. Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice. Biol Reprod. 2020 Feb 12;102(1):102-15.
 Hornos Carneiro MF, et al. Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline. Genetics. 2020 Feb;214(2):381-95.
 Xu Y, et al. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial. Reprod Biol Endocrinol. 2018 Mar 27;16(1):29.
 Bentov Y, et al. Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment. Clin Med Insights Reprod Health. 2014 Jun 8;8:31-6.
 Thakker D, et al. N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Obstet Gynecol Int. 2015;2015:817849.
 Chandil N, et al. Comparison of Metformin and N Acetylcysteine on Clinical, Metabolic Parameter and Hormonal Profile in Women with Polycystic Ovarian Syndrome. J Obstet Gynaecol India. 2019 Feb;69(1):77-81.
 Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ. 2007 Sep 29;335(7621):663-6.
 Ben-Meir A, et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell. 2015 Oct;14(5):887-95.
 Alleva R, et al. The protective role of ubiquinol-10 against formation of lipid hydroperoxides in human seminal fluid. Mol Aspects Med. 1997;18 Suppl:S221-8.
 Dutta S, et al. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J Urol. 2019 Apr 24;17(2):87-97.
 Mishra AK, et al. Insights into pH regulatory mechanisms in mediating spermatozoa functions. Vet World. 2018 Jun;11(6):852-58.
 Hosseinzadeh Colagar A, et al. Correlation of sperm parameters with semen lipid peroxidation and total antioxidants levels in astheno- and oligoasheno- teratospermic men. Iran Red Crescent Med J. 2013 Sep;15(9):780-5.
 Agarwal A, et al. Effect of oxidative stress on male reproduction. World J Mens Health. 2014 Apr;32(1):1-17.
 Gu NH, et al. Comparative analysis of mammalian sperm ultrastructure reveals relationships between sperm morphology, mitochondrial functions and motility. Reprod Biol Endocrinol. 2019 Aug 15;17(1):66.
 Amaral A, et al. Mitochondria functionality and sperm quality. Reproduction. 2013 Oct 1;146(5):R163-74.
 Vasan SS. Semen analysis and sperm function tests: How much to test? Indian J Urol. 2011 Jan;27(1):41-8.
 Vaamonde D, et al. Coenzyme Q10 in fertility and reproduction. In: López Lluch G, ed. Coenzyme Q in Aging. Cham, Switzerland: Springer; 2020:283-308.
 Mancini A, et al. Coenzyme Q10 concentrations in normal and pathological human seminal fluid. J Androl. 1994 Nov-Dec;15(6):591-4.
 Lewin A, Lavon H. The effect of coenzyme Q10 on sperm motility and function. Mol Aspects Med. 1997;18 Suppl:S213-9.
 Mancini A, Balercia G. Coenzyme Q(10) in male infertility: physiopathology and therapy. Biofactors. 2011 Sep-Oct;37(5):374-80.
 Thakur AS, et al. Effect of ubiquinol therapy on sperm parameters and serum testosterone levels in oligoasthenozoospermic infertile men. J Clin Diagn Res. 2015 Sep;9(9):BC01-3.
 Alahmar AT. The impact of two doses of coenzyme Q10 on semen parameters and antioxidant status in men with idiopathic oligoasthenoteratozoospermia. Clin Exp Reprod Med. 2019 Sep;46(3):112-8.
 Nadjarzadeh A, et al. Effect of Coenzyme Q10 supplementation on antioxidant enzymes activity and oxidative stress of seminal plasma: a double-blind randomised clinical trial. Andrologia. 2014 Mar;46(2):177-83.
 Safarinejad MR. The effect of coenzyme Q₁₀ supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. Int Urol Nephrol. 2012 Jun;44(3):689-700.
 Amjad S, et al. Role of Antioxidants in Alleviating Bisphenol A Toxicity. Biomolecules. 2020 Jul 25;10(8):1105.
 He X, et al. Hydrogen-rich Water Exerting a Protective Effect on Ovarian Reserve Function in a Mouse Model of Immune Premature Ovarian Failure Induced by Zona Pellucida 3. Chin Med J (Engl). 2016 Oct 5;129(19):2331-7.
 Begum R, et al. Molecular hydrogen may enhance the production of testosterone hormone in male infertility through hormone signal modulation and redox balance. Med Hypotheses. 2018 Dec;121:6-9.
 Meng X, et al. Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. Exp Ther Med. 2015 Dec;10(6):2277-82.
 Chuai Y, et al. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem J. 2012 Feb 15;442(1):49-56.
[CD1]Link to article about vitamins/minerals and reproductive health
[CD2]Insert link to Molecular Hydrogen resource center