Review question: Do supplementary oral antioxidants compared with placebo, no treatment/standard treatment or another antioxidant improve fertility outcomes for subfertile women (standard treatment includes folic acid < 1 mg).
Background: many subfertile women undergoing fertility treatment also take dietary supplements in the hope of improving their fertility. This can be a very stressful time for women and their partners. It is important that these couples be given high quality evidence that will allow them to make informed decisions on whether taking a supplemental antioxidant when undergoing fertility treatment will improve their chances or cause any adverse effects; this is especially important as most antioxidant supplements are uncontrolled by regulation. This review aimed to assess whether supplements with oral antioxidants increase a subfertile woman's chances of becoming pregnant and having a baby.
Search date: The evidence is current to April 2013.
Study characteristics: The review included 28 randomised controlled trials that compared antioxidants with placebo or no treatment/standard treatment, or with another antioxidant in a total of 3548 women.
Funding sources: Funding sources were reported by only six of the 28 included trials.
Key results: Antioxidants were not found to be effective for increasing rates of live birth or clinical pregnancy. Based on these results, we would expect that out of 100 subfertile women not taking antioxidants, 23 would become pregnant, compared with between 22 and 36 per 100 who would become pregnant if taking antioxidants to improve their chances of becoming pregnant. Antioxidants did not appear to be associated with the adverse events of miscarriage or multiple or ectopic pregnancy.
Quality of the evidence: The quality of the evidence in this review for live birth, clinical pregnancy and adverse effects was rated 'very low' to 'low'.

Antioxidants for female subfertility

Mitochondria produce adenosine triphosphate (ATP) while also generating high amounts of reactive oxygen species (ROS) derived from oxygen metabolism. ROS are small but highly reactive molecules that can be detrimental if unregulated. While normally functioning mitochondria produce molecules that counteract ROS production, an imbalance between the amount of ROS produced in the mitochondria and the capacity of the cell to counteract them leads to oxidative stress and ultimately to mitochondrial dysfunction. This dysfunction impairs cellular functions through reduced ATP output and/or increased oxidative stress. Mitochondrial dysfunction may also lead to poor oocyte quality and embryo development, ultimately affecting pregnancy outcomes. Improving mitochondrial function through antioxidant supplementation may enhance reproductive performance. Recent studies suggest that antioxidants may treat infertility by restoring mitochondrial function and promoting mitochondrial biogenesis. However, further randomized, controlled trials are needed to determine their clinical efficacy. In this review, we discuss the use of resveratrol, coenzyme-Q10, melatonin, folic acid, and several vitamins as antioxidant treatments to improve human oocyte and embryo quality, focusing on the mitochondria as their main hypothetical target. However, this mechanism of action has not yet been demonstrated in the human oocyte, which highlights the need for further studies in this field.

https://www.mdpi.com/2076-3921/9/12/1197/pdf

Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: A Review.

For most infertile couples, in vitro fertilization (IVF) represents the only chance to conceive. Given the limited success of IVF procedures, novel approaches are continuously tested with the aim of improving IVF outcomes. Growing attention is devoted today to the potential benefit of natural antioxidants in the optimization of infertility treatments. This review summarizes current data in this context, focusing on both experimental studies on oocytes/embryos and clinical trials on antioxidants supplementation. Based on information gained from experimental studies, antioxidant supplementation may have beneficial effects on IVF outcomes in terms of quality and cryotolerance of in vitro produced embryos, together with positive effects on in vitro maturation oocytes and on early embryonic development. Unfortunately, from the clinical side, there is a paucity of evidence favoring the protective qualities of antioxidants. Among the antioxidants considered, coenzyme Q10 may be regarded as one of the most promising for its positive role in rescuing the oxidative stress-induced damages, but further data are needed. It is concluded that further trials are necessary to characterize the potential clinical value of antioxidants in IVF treatments.

/pdf/effects-of-supplementation-with-natural-antioxidants-on-ikahpus4v7.pdf

Effects of Supplementation with Natural Antioxidants on Oocytes and Preimplantation Embryos.

CONTEXT
The Mediterranean diet (MD) is a dietary pattern with evidence of positive health impact, and some nutrients in this diet have already been researched for their effectiveness in fertility. However, there are still questions about whether high adherence to the MD could be a factor that contributes to positive fertility outcomes in infertile men and women.


OBJECTIVE
A systematic review and meta-analysis were conducted to determine whether a greater adherence to the MD can improve fertility markers and outcomes in infertile men and women.


DATA SOURCES
The MEDLINE, BVS, SciELO, CENTRAL, and Embase databases and gray literature were searched from their inception to May 2022.


STUDY SELECTION
Data were included from cohort studies that addressed MD and outcomes.


DATA EXTRACTION
Data searches, article selection, data extraction, and risk-of-bias assessments were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.


RESULTS
A total of 11 studies met the inclusion criteria (n = 13 157 women and 1338 men). Greater adherence to the MD was associated with live births (I2 = 83.16%; odds ratio [OR], 0.652; 95%CI, 0.408-3.194), pregnancy rate (I2 = 93.83%; OR, 1.192; 95%CI, 0.349-4.325), sperm concentration >15 × 106/mL (I2 = 32.97%; OR 2.862; 95%CI, 1.583-5.174), and sperm count > 39 × 106/mL (I2 = 48.1%; OR, 2.543; 95%CI, 1.319-4.904); however, in an inconsistent scenario regarding the meta-analysis.


CONCLUSION
Current evidence of high adherence to MD and fertility markers is insufficient to support their clinical application, even though it indicates sperm improvement and a possibility of better pregnancy outcomes.


SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. 169396.

Mediterranean diet and infertility: a systematic review with meta-analysis of cohort studies.

Vitamin E is known as an essential vitamin, and many studies had demonstrated the importance of vitamin E throughout the reproductive process, such as miscarriage, premature birth, preeclampsia, and intrauterine growth restriction, which could be caused by a lack of vitamin E during pregnancy. Its potent antioxidant properties can counteract the oxidative stress induced by oxygen free radicals and imbalance of oxidative-antioxidant levels, hence it may play a role in maintaining the normal function of the female reproductive system. Despite the fact that vitamin E is acknowledged as the substance needed for reproduction, its beneficial effects on female fertility, gynaecological health, and diseases are still poorly understood and lacking. Therefore, the goal of this paper is to provide a summary of the known roles of vitamin E supplementation in women for gynaecological health and reproductive-related diseases, as well as its future perspective.

/pdf/are-vitamin-e-supplementation-beneficial-for-female-297kisqd.pdf

Are Vitamin E Supplementation Beneficial for Female Gynaecology Health and Diseases?

Objective: Good oocyte quality and maturity are important prerequisites for high fertilization and implantation rates in IVF/ ICSI treatment cycles. Reactive oxygen species (ROS) are produced within ovarian follicles, especially during the ovulation process, and increased ROS activity may be a cause of impaired oocyte maturation and higher rate of failure of IVF/ ICSI cycles. Study design: RCT evaluating the effect of antioxidant supplementation on ICSI/IVF outcomes. Two hundred and eighteen women with unexplained subfertility undergoing IVF/ICSI were randomized into two groups. The study group ( n 112) received daily oral antioxidants in the form of multivitamins and minerals (amino acid chelated) while the control group ( n 106) did not. Main outcomes were number of mature metaphase II (MII) oocytes and clinical pregnancy rate. Results: There were no signifi cant changes between the groups as regards age, BMI, basal FSH, number of mature (MII) oocytes (12.7 9.4 vs. 13.2 8.6, P 0.7) and clinical pregnancy rate per woman randomized (38% vs. 34%; [OR 1.2; 95% CI, 0.70 – 2.11]. Conclusion: Oral antioxidants in the form of a combination of multivitamins and minerals (amino acid chelated) did not improve oocyte quality and pregnancy rates in women with unexplained infertility undergoing IVF/ICSI treatment.

Oral antioxidants supplementation for women with unexplained infertility undergoing ICSI/IVF: randomized controlled trial

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Oral antioxidants supplementation for women with unexplained infertility undergoing ICSI/IVF: randomized controlled trial