Antioxidant Supplementation on Fertility

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 15319

Special Issue Editors


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Guest Editor
Associate Professor, Department of Urology, Aristotle University School of Medicine, Thessaloniki, Greece
Interests: male infertility; oxidative stress; antioxidant defenses; antioxidant supplementation; redox mechanisms of drugs; reactive oxygen species (ROS); lipid peroxidation; reactive nitrogen species (RNS); varicocele; microsurgical operations in andrology

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Guest Editor
Professor, Department of Urology, School of Medicine, Ioannina University, 45500 Ioannina, Greece
Interests: male infertility; varicocele; microsurgical operations in andrology
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Special Issue Information

Dear Colleagues,

Couples’ subfertility may be attributable to male factors, female factors, or a combination of both. However, no etiological factors have been detected in the infertile couples subpopulation. These couples are characterized as having idiopathic infertility. It is has been proposed that oxidative stress (OS) is involved in the pathophysiology of subfertility, and antioxidants are thought to reduce the detrimental consequences of OS, which are manifested both in the standard parameters of analysis and in the outcome of sperm functional assays in subfertile couples. Moreover, OS has been implicated in several placental disorders and pregnancy pathologies. Systemic disorders and conditions leading to infection and inflammation are commonly attributed to enhanced OS; thus, the discovery of inflammatory markers and treatment modalities will have major clinical implications for male infertility. Diet might also affect couples’ reproductive potential, although the involved biochemical mechanisms remain poorly elucidated. In the last decade, the consumption of organic food has increased worldwide, with consumers hoping to reduce the risk of developing chronic diseases despite the scarce scientific evidence supporting this phenomenon. In addition, available knockout animal models might help us to better understand the role of different antioxidant enzymes in male reproductive capacity, and the development of novel animal models lacking different antioxidants is crucial to understanding the consequences of high ROS levels in the human reproductive chain.

Oocytes have only a limited capacity to repair sperm-derived decays, and therefore reducing sperm DNA damage linked to OS represents a promising approach. For example, a detailed analysis of DNA fragmentation or lack of nuclear condensation is mandatory prior to any treatment. Antioxidants represent readily available and inexpensive pharmaceutical compounds. On the other hand, there is a lack of high-quality evidence demonstrating antioxidant administration’s effect on infertile couples, whether beneficial or detrimental. Instead, antioxidant supplements with ambiguous efficiency and potentially detrimental effects are often given arbitrarily. For that reason, oxidation reduction has emerged as a viable ancillary tool for basic semen analysis, measuring the overall balance between oxidative and reductive stress.

This Special Issue is open to all investigations exploring antioxidant supplementation for fertility and providing preliminary findings with potential for clinical translation. Topics of interest include, but are not limited to:

  • Effect of antioxidant supplementation on male fertility;
  • Effect of antioxidants on sperm genetic damage and sperm energetic metabolism;
  • Effect of antioxidant supplementation on female fertility;
  • Oxidative stress in pregnancy and fertility pathologies;
  • Effect of antioxidant supplementation on conventional and advanced sperm function tests;
  • The role of infection and inflammation-mediated OS in fertility;
  • Investigation of antioxidant enzymes and male fertility through knockout animal models;
  • Diet and its impact on fertility.

We look forward to receiving your contributions.

Dr. Fotios Dimitriadis
Prof. Dr. Nikolaos Sofikitis
Guest Editors

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Keywords

  • oxidative stress
  • antioxidants
  • couple subfertility
  • OS-mediated sperm genetic damage
  • OS and conventional or advanced sperm function tests
  • infection and inflammation-mediated OS

Published Papers (6 papers)

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Research

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17 pages, 926 KiB  
Article
Effect of Micronutrients and L-Carnitine as Antioxidant on Sperm Parameters, Genome Integrity, and ICSI Outcomes: Randomized, Double-Blind, and Placebo-Controlled Clinical Trial
by Marwa Lahimer, Oumaima Gherissi, Nesrine Ben Salem, Henda Ben Mustapha, Véronique Bach, Hafida Khorsi-Cauet, Hedi Khairi, Habib Ben Ali, Moncef BenKhalifa and Mounir Ajina
Antioxidants 2023, 12(11), 1937; https://doi.org/10.3390/antiox12111937 - 31 Oct 2023
Viewed by 3167
Abstract
The evaluation of sperm DNA integrity is recommended in the sixth edition of the 2021 World Health Organization guidelines. Oxidative stress has been identified as a crucial factor leading to genome decay, lipid peroxidation, and nucleoprotein oxidation. This double-blind, placebo-controlled clinical trial aimed [...] Read more.
The evaluation of sperm DNA integrity is recommended in the sixth edition of the 2021 World Health Organization guidelines. Oxidative stress has been identified as a crucial factor leading to genome decay, lipid peroxidation, and nucleoprotein oxidation. This double-blind, placebo-controlled clinical trial aimed to assess the effect of oral antioxidant treatment (Fertilis), which contains L-carnitine and some micronutrients, in the improvement of conventional sperm parameters, sperm DNA integrity and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. A total of 263 participants were enrolled and randomly divided into two groups: 131 participants received the antioxidant treatment, while 132 participants received a placebo. The male partners in both groups underwent the antioxidant treatment or the placebo for a duration of three months. For each participant, we performed a hormonal test, an infectious test, a spermogram, a TUNEL assay for sperm DNA fragmentation, a toluidine blue staining for sperm DNA decondensation, and an IVF/ICSI procedure. Sperm characteristics analysis (volume, count, motility, and vitality), sperm DNA fragmentation, and sperm DNA decondensation were assessed and compared to the results preceding the antioxidant treatment. The study outcome revealed a significant decrease in the DNA fragmentation index and a significant increase in sperm motility after 3 months of treatment (p = 0.01 and p = 0.02, respectively). Additionally, a significant improvement in clinical pregnancy rate (p = 0.01) and life birth rate (p = 0.031) was observed. No significant changes were observed in conventional sperm parameters (volume, count, and vitality) or sperm DNA decondensation (SDI). Antioxidant therapy has a beneficial impact on achieving pregnancy, whether through spontaneous conception or assisted reproductive procedures (ART). Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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13 pages, 1991 KiB  
Article
Antioxidants in Male Infertility—If We Want to Get This Right We Need to Take the Bull by the Horns: A Pilot Study
by Usha Punjabi, Ilse Goovaerts, Kris Peeters and Diane De Neubourg
Antioxidants 2023, 12(10), 1805; https://doi.org/10.3390/antiox12101805 - 27 Sep 2023
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Abstract
Antioxidant therapy should be reserved for infertile patients who actually exhibit signs of oxidative stress (OS). Nevertheless, there is no consensus regarding the measure of the primary endpoint and the assay that should be used. The formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG), an early marker [...] Read more.
Antioxidant therapy should be reserved for infertile patients who actually exhibit signs of oxidative stress (OS). Nevertheless, there is no consensus regarding the measure of the primary endpoint and the assay that should be used. The formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG), an early marker of sperm DNA oxidation (SDO), was analyzed using flow cytometry, in men at a University hospital setup for infertility treatment. Similar to conventional semen parameters, 8-OHdG assay was validated on fresh semen samples to reduce the variability of results. SDO was associated with semen volume, sperm concentration, leucocytes and round cells, but not with age, body mass index, sperm DNA fragmentation (SDF) or OS. Whether the semen samples were normal or subnormal according to the WHO criteria, the expression of 8-OHdG was not different. Receiver operating characteristic curve analysis could discriminate two independent populations. Both SDF and SDO were independently expressed. A high SDF did not reveal a high SDO and vice versa. The thresholds for SDO have been established, but vary with the techniques used. The methodology for SDO needs to be further validated and optimized on a larger clinically defined patient population before the outcome measure is fit to monitor antioxidant therapy in male infertility. Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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14 pages, 512 KiB  
Article
CYP19A1 TC/CC Polymorphism, along with Deletion of GSTM1 and GSTT1 Genes, Strongly Influences Female Infertility Risk
by Maria Manuel Casteleiro Alves, Micaela Almeida, António Hélio Oliani, Luiza Breitenfeld and Ana Cristina Ramalhinho
Antioxidants 2023, 12(4), 940; https://doi.org/10.3390/antiox12040940 - 16 Apr 2023
Cited by 1 | Viewed by 1463
Abstract
Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with [...] Read more.
Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with established infertility and 161 fertile female controls was performed, and statistical associations were analyzed. For carriers of GSTM1 null genotype along with CYP19A1 C allele, there is a significant association with female infertility risk (OR 7.023; 95% CI (3.627–13.601; p < 0.001), and, also for carriers of GSTT1 null genotype along with the CYP19A1 TC/CC genotype (OR 24.150; 95% CI (11.148–52.317; p < 0.001). A positive association with female infertility risk for carriers of the C allele in CYP19A1 and null genotypes in GTSM1 (OR 11.979; 95% CI (4.570–31.400; p < 0.001) or GSTT1 (OR 13.169; 95% CI (4.518–38.380; p < 0.001) was found. When both GSTs are deleted, the risk of developing female infertility is significant, independently of the CYP19A1 genotype; when all the presumed high-risk genotypes are present, we found a significant association with female infertility risk (OR 47,914; 95% CI (14,051–163,393; p < 0.001). Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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Review

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21 pages, 908 KiB  
Review
The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency
by Andrew N. Shelling and Noha Ahmed Nasef
Antioxidants 2023, 12(8), 1601; https://doi.org/10.3390/antiox12081601 - 11 Aug 2023
Cited by 5 | Viewed by 4369
Abstract
Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility [...] Read more.
Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility in women and POI. In this review, we discuss the mechanisms of oxidative stress implicated in ovarian ageing and dysfunction in relation to POI, in particular mitochondrial dysfunction, apoptosis and inflammation. Genetic defects, autoimmunity and chemotherapy, are some of the reviewed hallmarks of POI that can lead to increased oxidative stress. Additionally, we highlight lifestyle factors, including diet, low energy availability and BMI, that can increase the risk of POI. The final section of this review discusses dietary factors associated with POI, including consumption of oily fish, mitochondria nutrient therapy, melatonin, dairy and vitamins that can be targeted as potential interventions, especially for at-risk women and in combination with personalised nutrition. Understanding the impact of lifestyle and its implications for POI and oxidative stress holds great promise in reducing the burden of this condition. Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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22 pages, 1324 KiB  
Review
The Silent Threat to Women’s Fertility: Uncovering the Devastating Effects of Oxidative Stress
by Aris Kaltsas, Athanasios Zikopoulos, Efthalia Moustakli, Athanasios Zachariou, Georgia Tsirka, Chara Tsiampali, Natalia Palapela, Nikolaos Sofikitis and Fotios Dimitriadis
Antioxidants 2023, 12(8), 1490; https://doi.org/10.3390/antiox12081490 - 26 Jul 2023
Cited by 6 | Viewed by 2957
Abstract
Oxidative stress (OS), which arises through an imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses, plays a key role in the pathophysiology of female infertility, with the latter constituting just one of a number of diseases linked to OS [...] Read more.
Oxidative stress (OS), which arises through an imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses, plays a key role in the pathophysiology of female infertility, with the latter constituting just one of a number of diseases linked to OS as a potential cause. The aim of the present article is to review the literature regarding the association between OS and female infertility. Among the reproductive diseases considered are endometriosis and polycystic ovary syndrome (PCOS), while environmental pollutants, lifestyle variables, and underlying medical conditions possibly resulting in OS are additionally examined. Current evidence points to OS likely contributing to the pathophysiology of the above reproductive disorders, with the amount of damage done by OS being influenced by such variables as duration and severity of exposure and the individual’s age and genetic predisposition. Also discussed are the processes via which OS may affect female fertility, these including DNA damage and mitochondrial dysfunction. Finally, the last section of the manuscript contains an evaluation of treatment options, including antioxidants and lifestyle modification, capable of minimizing OS in infertile women. The prime message underlined by this review is the importance of considering OS in the diagnosis and treatment of female infertility. Further studies are, nevertheless required to identify the best treatment regimen and its ideal duration. Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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12 pages, 771 KiB  
Review
The Role of Seminal Oxidative Stress in Recurrent Pregnancy Loss
by Rhianna Davies, Channa N. Jayasena, Raj Rai and Suks Minhas
Antioxidants 2023, 12(3), 723; https://doi.org/10.3390/antiox12030723 - 15 Mar 2023
Cited by 3 | Viewed by 1438
Abstract
Recurrent pregnancy loss is a distressing condition affecting 1–2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male [...] Read more.
Recurrent pregnancy loss is a distressing condition affecting 1–2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male reproduction but in excess are suspected to generate structural and functional damage to the sperm. Evidence is mounting to support an association between elevated seminal reaction oxygen species and recurrent pregnancy loss. Studies suggest that the rates of sperm DNA damage are higher in the male partners of women affected by recurrent pregnancy loss compared with unaffected men. However, the available pool of data is conflicting, and interpretation is limited by the recent change in nomenclature and the heterogeneity of study methodologies. Furthermore, investigation into the effects of oxidative stress on the epigenome show promise. The value of antioxidant therapy in the management of recurrent pregnancy loss currently remains unclear. Full article
(This article belongs to the Special Issue Antioxidant Supplementation on Fertility)
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