Nutrition + Egg Quality: Part 2

Following on from Nutrition for Egg Quality Part 1, here we will discuss the clinical research and indications for Inositol, Vitamin E and Omega 3 fatty acids in relation to improving egg quality and enhancing fertility.

INOSITOL

Inositol is a B complex vitamin which has been researched for its ability to increase egg quality, particularly in women with polycystic ovarian syndrome (PCOS). (1) PCOS leads to chronic anovulatory cycles, often leading to infertility. A study on 34 women under 40 years with PCOS analysed the effects of D-chiro-inositol on oocyte quality. Women were divided into either Group A (receiving 2 g of myo-inositol + 200 µg of folic acid) or Group B (receiving only 200 µg of folic acid); treatment was twice daily for three months. Follicle numbers with a diameter >15mm and the quantity of oocytes retrieved at the pick-up were significantly greater in the inositol-treatment group. Group A also had a significant decrease in the mean number of immature oocytes and degraded oocytes. (1)

Another study on 50 infertile women with PCOS who were undergoing artificial reproductive technology (ART) examined the effect of daily doses of 4 g myo-Inositol combined with 400 mg folic acid or 400 mg folic acid alone (control). (2) This began one month prior to starting the antagonist cycle until the day of ovum pick up. It was found that percentage of metaphase II oocyte (mature), rate of fertilisation and embryo quality significantly improved in the myo-inositol group. The percentage of poor quality embryos in the intervention group also significantly decreased compared to controls. Gene expressions indicating developmental competence of oocytes were significantly higher in the intervention group also. (2)

Whilst the above two studies analyse women with PCOS, a study conducted on 100 women aged <40 years who were going through multiple follicular stimulation and ART. (3) The intervention group received myo-inositol and folic acid for three months before stimulation and during the stimulation period itself. The control group received folic acid alone in the three months prior and throughout stimulation treatment. Whilst stimulation period lengths were similar between groups, there was a significant decrease in the amount of gonadotropins (hormones) needed to reach follicular maturation in the myo-inositol group. The number of oocytes retrieved in the myo-inositol group was also significantly reduced yet clinical pregnancy and implantation rates were similar between groups. This demonstrates that myo-inositol may reduce the hormone dose needed and number of oocytes retrieved to maintain the same clinically pregnancy rate. (3)

MYO-INOSITOL BENEFITS:

- Increases the number of viable oocytes

- Increases the quality of oocytes (less degenerated oocytes)

- Improved embryo quality and decreased numbers of poor embryos

- Improved oocyte developmental progress (indicated by gene expression)

- Reduced need for gonadotropin hormones

INOSITOL RICH FOODS:

- Fresh fruits and vegetables are the best source of myo-inositol! Fruit sources include oranges, pears, bananas, peaches

- Vegetables including capsicum, leafy greens, tomatoes and potatoes

- Whole grains like brown rice, bran and oats

- Legumes (lentils, chickpeas, black beans, white beans)

- Nuts


VITAMIN E

Vitamin E is a fat-soluble vitamin that is made up of tocopherols and tocotrienols. It acts a potent antioxidant in the body and it is for this reason that it has a role in promoting fertility and conception health. A recent 2019 study on 40 women with failed implantation analysed the effects of vitamin E supplementation (400 IU) over 12 weeks.(4) Compared to women in the control group, as expected, in the intervention group serum vitamin E levels were significantly higher. Importantly, endometrial thickness was significantly greater with vitamin E supplementation, along with significantly reduced malondialdehyde levels. Malondialdehyde is a marker of lipid oxidation; thus vitamin E acts to protect lipids from oxidative stress. Vitamin E also down-regulated gene expression tumour necrosis factor alpha, interleukin-1 and low-density lipoprotein receptor. (4)

Another study on women with unexplained infertility who were undergoing controlled ovarian stimulation and intrauterine insemination demonstrated the effects of vitamin E supplementation (400 IU). (5) Whilst there were no significant increases in pregnancy or implantation rates, there were significant increases in endometrial thickness in the vitamin E group. Clomiphene citrate is the drug used for ovarian stimulation however a known side effect is endometrial thinning; this study indicated that vitamin E may mitigate this effect. The effects of vitamin E are believed to be due to antioxidant and anticoagulant actions. The anti-coagulant action may increase blood flow to the endometrium and may increase blood flow to developing follicles, increasing oestrogen production supporting endometrium growth. (5)

VITAMIN E BENEFITS:

- Increases endometrial thickness making implantation more likely

- Potent antioxidant, particularly protects lipids from oxidative stress

- Down-regulates inflammatory gene expression

- May mitigate the side effect of endometrial thinning due to ovarian stimulation

VITAMIN E RICH FOODS:

- Rice

- Wheat bran

- Oats

- Walnuts

- Pepitas (pumpkin seeds)

OMEGA 3 FATTY ACIDS

Omega-3 polyunsaturated fatty acids encompass alpha linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. Omega-3’s have the ability to downregulate inflammation as well as being components of cell membranes and hormone precursors. It is for these reasons that research into their ability to enhance egg quality has been conducted.

One study analysed the effects of omega 3 supplementation on sub-fertile women aged 20-40 years that were undergoing intra-cytoplasmic sperm injection. (6) For eight weeks, women were either prescribed 1000mg of an omega 3 supplement or a control. In the intervention group, the ratio of follicles injected to retrieved oocytes was higher, along with an increase in the amount of metaphase II oocytes, fertilization rate and grade I embryos. (6)

Another study investigated the correlation between serum omega 3 fatty acid levels in 100 women going through ART and success rate. (7) It was found that higher serum levels of long-chain omega-3 polyunsaturated fats were positively correlated with increased probability of clinical pregnancy and live birth. Interestingly, serum omega-6 fatty acids nor total polyunsaturated fatty acids (omega-3 and omega-6) were correlated with increased clinical outcomes. (7)

OMEGA 3 BENEFITS:

- Improved oocyte and embryo quality

- Increased fertilisation rates

- Higher serum levels of omega 3 fatty acids correlated with greater clinical pregnancy and live birth rates

OMEGA 3 RICH FOODS:

- The best source is fatty fish (sardines, herring, mackerel, salmon)

- Cod liver oil

- Nuts and seeds (walnuts, flaxseeds, chia seeds)

- Free range eggs

- Grass-fed meat (organic if possible)


This article was written by Annabel Murray as part of her internship with me in 2020.

References

1. Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F. Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: A double blind trial. Eur Rev Med Pharmacol Sci [Internet]. 2011 May;15(5):509–14. PMID:21744744

2. Akbari Sene A, Tabatabaie A, Nikniaz H, Alizadeh A, Sheibani K, Mortezapour Alisaraie M, et al. The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: A randomized clinical trial. Arch Gynecol Obstet [Internet]. 2019 Jun;299(6):1701–7. doi:10.1007/s00404-019-05111-1

3. Lisi F, Carfagna P, Oliva MM, Rago R, Lisi R, Poverini R, et al. Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: A pilot study. Reprod Biol Endocrin [Internet]. 2012 Jul;10:52. doi:10.1186/1477-7827-10-52

4. Hashemi Z, Sharifi N, Khani B, Aghadavod E, Asemi Z. The effects of vitamin E supplementation on endometrial thickness, and gene expression of vascular endothelial growth factor and inflammatory cytokines among women with implantation failure. J Matern-Fetal Neo M [Internet]. 2019 Jan;32(1):95–102. doi: 10.1080/14767058.2017.1372413

5. 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 [Internet]. 2012 Apr;29(4):325–8. doi: 10.1007/s10815-012-9714-1

6. Alousi TAA-, Allak MMAA-, Aziz AA, Ghazali BSA. The effect of omega-3 on the number of retrieved ova, fertilization rate, and embryo grading in subfertile women undergoing intracytoplasmic sperm injection. Biomed Pharmacol [Internet]. 2018;(4):2221. doi:10.13005/bpj/1605

7. Chiu Y-H, Karmon AE, Gaskins AJ, Arvizu M, Williams PL, Souter I, et al. Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Human reproduction (Oxford, England) [Internet]. 2018 Jan 1;33(1):156–65. doi: 10.1093/humrep/dex335

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