When discussing female reproductive health, allow us to set the scene by defining and exploring some terms. Ovarian follicles are housed within the ovaries and are fluid filled sacs which contain a developing egg (oocyte). Each cycle, multiple eggs/follicles will develop but one egg will be released during ovulation (however, when undergoing egg retrieval multiple eggs/follicles will be selected and removed during the same cycle). Perhaps you have heard the term “ovarian reserves?” This refers to the number of follicles in the ovaries and reflects the quantity of available eggs. In recent years, however, egg quality has been of growing interest. A number of factors contribute to the overall health and quality of eggs including hormones, the egg, and the follicle. In this article, we will explore these factors and nutritional support strategies.

Hormones (our favorite!) govern and regulate many processes in our bodies including reproductive health. Three hormones of particular interest in the reproductive process include Follicle Stimulating Hormone (FSH), Estradiol, and Antimullerian Hormone (AMH). The pituitary gland (a small, hormone-producing gland in the brain) produces FSH. This hormone stimulates follicle growth and egg maturation. As follicles grow and mature (thanks to FSH), the follicles begin releasing another hormone: estradiol (a form of estrogen). Therefore, estradiol levels are an indicator of follicular development. In fact, when the pituitary gland senses high estradiol levels, it will take it as a cue to decrease FSH production (because it recognizes follicle development has been achieved). AMH is another hormone which acts as an indicator of ovarian reserves. While higher levels of AMH indicate a higher number of follicles/eggs and may provide insight to providers, it does not indicate likelihood of pregnancy nor the health or quality of the eggs. Finally, while insulin is not considered a reproductive hormone, high levels can lead to increased androgen production and thereby negatively impact ovulation and egg quality (this is most common in cases involving diabetes and/or PCOS).

Beyond hormones, the health of the egg and follicle also matter. Oocytes (eggs) are the largest cells found in the female body. These cells also have the greatest concentration of mitochondria (the energy producer and “powerhouse of the cell”) and will undergo unique cell division processes compared to other cells. As for follicles, they serve to promote and protect the eggs. Ideally, follicles release hormones which promote reproductive processes. Follicles also ought to be rich in antioxidants to protect the egg. Therefore, strategies which support the mitochondria and proper cell division of oocytes and bolster and enhance the follicular fluid may promote egg quality.

Nutrition Support and Interventions:
As discussed, while it was once thought that promoting egg quantity was key, in recent years focus has shifted to promoting egg/follicle quality. With this in mind, we have compiled a handful of tips to support the body, ovarian environment, and potentially promote egg/follicle quality. While these strategies apply generally to women of reproductive age, they are particularly relevant for specific subpopulations: Those attempting to get pregnant, retrieve/freeze their eggs, and/or undergo IVF in the near future. Keep in mind that the follicle maturation process occurs over about 90 days (from primordial follicle to mature egg), so it is recommended to introduce these nutritional components at least 3 months prior; however, it is ideal to implement these strategies as early as possible.

General Health Tips:
Ensure you are meeting your caloric, protein, and hydration needs. Adequate intake is crucial to overall health of tissues, hormones, and body systems and processes. Additional components which support and promote overall health include adequate sleep, regular physical activity, exposure to natural light, glucose/insulin management, and regular bowel movements (preferably 1-2 per day). Good routines in these areas will support your overall physical health status. An anti-inflammatory diet can also support overall health and potentially improve the ovarian environment by decreasing inflammation. Increasing intake of omega 3 rich food sources (fish, nuts, seeds, etc) can help towards this end.

Nutrition Support and Interventions:
While it was once thought that promoting egg quantity was a key factor to the success of egg retrieval/freezing, in recent years focus has shifted to promoting egg quality. With this in mind, we have compiled a handful of tips to support the body and potentially promote egg quality. Keep in mind that the complete follicle/egg development process occurs over about 90 days (from primordial follicle to mature egg), so it may be ideal to introduce these nutritional components at least 3 months prior to your procedure.

 

Specific Nutrients:

• CoQ10: Some studies indicate CoQ10 improves oocyte maturation (a process known as meiotic maturation) by enhancing cellular energy production (mitochondrial function) and decreasing damage to the oocyte (by suppressing oxidative stress and improving oxidative metabolism of the follicular fluid).
  • Food Sources of CoQ10: Organ meats, fatty fish, meat, soybeans, vegetables, nuts and seeds.
• Melatonin: Numerous studies have also explored melatonin as it relates to improved egg quality. In fact, increased levels of melatonin in the follicular fluid may be an indicator of oocyte quality and are associated with better fertility outcomes. Melatonin in the follicular fluid correlates with age and is thought to be protective against age related follicular weakness and damage: Promising results have been observed regarding melatonin’s capacity to protect against aging-induced fertility decline. A 2017 study in mice suggests, “Melatonin delays ovarian aging by multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT expression and ribosome function, and by reducing autophagy” (See “Long-term melatonin treatment delays ovarian aging”).
  • Food Sources of Melatonin: Tart cherry (i.e. tart cherry juice), Goji berries, eggs, milk, fish, nuts. Other sources: Melatonin can be obtained exogenously (externally: through diet) or endogenously (internally: produced by the body). There are a number of ways to support endogenous melatonin production including prioritizing exposure to natural light, reducing exposures to artificial light (i.e. limiting screen time and dimming lights prior to bed time), reducing coffee consumption (which disrupts melatonin production), and establishing life rhythms and practices that reduce stress and promote relaxation.

• Resveratrol: Several animal studies suggest another antioxidant, resveratrol, may also serve to improve egg quality. While exact mechanisms are unknown and further research is needed, it is thought that resveratrol is protective against free radicals and may improve the ovarian environment and functions. In mammals, it may decrease postovulatory aging (POA) of eggs thereby improving oocyte quality.
  • Food Sources of Resveratrol: Red grapes (and wine), peanuts, pistachios, dark berries (blueberries, cranberries, bilberries, red currents, lingonberries, mulberries, etc), soy, Itadori tea, dark chocolate.
• Inositol: Also known as Vitamin B8, inositol (specifically: myo-inositol and D-chiro-inositol) has been explored for its potential impacts on PCOS. Studies have also demonstrated it may improve oocyte and embryo quality. Improvements in insulin sensitivity, serum triglycerides, blood pressure and endocrine factors (levels of androgens, follicle stimulating hormone, luteinizing hormone, sex-hormone binding globulin, etc) have also been observed.
  • Food Sources of Inositol: Beans, peas, brown rice, wheat bran, nuts, cantaloupe, bananas, raisins, cabbage, liver.
• Quercetin: Animal studies suggest quercetin may also improve oocyte quality and even prevent or delay oocyte aging.
  • Food Sources of Quercetin: Onions, kale, broccoli, blueberries, apples, cherry tomatoes, and capers.
• DHEA: Finally, there are also studies which suggest that DHEA may be a promising addition to the fertility equation: Studies suggest DHEA may improve ovarian function/reserves and improve fertility outcomes.
  • Food Sources of DHEA: There are no foods which serve as direct sources of DHEA. It is a hormone (an androgen) endogenously produced by our bodies in the adrenal glands. One way to support DHEA production is by supporting the health and function of the adrenal glands which can be accomplished through nutrition and lifestyle related strategies (i.e. exercise).

Supplements:
While we encourage and prioritize whole food sources and the food sources mentioned above offer some amounts of nutritional support, some individuals may benefit from supplementation. When supplementing, it is important to purchase from reputable sources which practice third party testing to uphold safety and quality standards. Functional Fueling Nutrition utilizes FullScript to give our patients access to professional grade supplements. To start a FullScript account, click here. Before beginning any new supplementation, consult with a Registered Dietitian to ensure the type and dosage is right for you!

In conclusion, promoting egg quality involves hormonal and physical health factors which can be supported through nutrition and lifestyle interventions. For optimal results, consider incorporating CoQ10, melatonin, resveratrol, inositol, quercetin, and/or DHEA support through nutrition, supplements, and/or lifestyle routines. If you enjoyed this discussion and would like to learn more or explore the possibility of working with us, click here to book a discovery call.

By Madison Morris (Dietetic Intern)

 

Resources and References:

Hormones and Ovarian Reserves: https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/ovarian-reserve/

Understanding the Female Reproductive Cycle: https://youtu.be/L4adODFmmtI

“CoQ10 Supplementation in Patients Undergoing IVF-ET: The Relationship with Follicular Fluid Content and Oocyte Maturity:” https://pubmed.ncbi.nlm.nih.gov/30322142/

“Melatonin effects on ovarian follicular cells: a systematic review:” https://pubmed.ncbi.nlm.nih.gov/31531613/

“Long-term melatonin treatment delays ovarian aging:” https://pubmed.ncbi.nlm.nih.gov/27889913/

“Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve:” https://pubmed.ncbi.nlm.nih.gov/28062641/

“Insufficiency of melatonin in follicular fluid is a reversible cause for advanced maternal age-related aneuploidy in oocytes:” https://pubmed.ncbi.nlm.nih.gov/31526949/

“Symposium review: Reduction in oocyte developmental competence by stress is associated with alterations in mitochondrial function:” https://pubmed.ncbi.nlm.nih.gov/29395145/

“Effect of Coenzyme Q10 and transcutaneous electrical acupoint stimulation in assisted reproductive technology: a retrospective controlled study:” https://pubmed.ncbi.nlm.nih.gov/36476305/

“Complementary effects of coenzyme Q10 and Lepidium sativum supplementation on the reproductive function of [male] mice: An experimental study:” https://pubmed.ncbi.nlm.nih.gov/34458669/

“DHEA use to improve likelihood of IVF/ICSI success in patients with diminished ovarian reserve: A systematic review and meta-analysis:” https://pubmed.ncbi.nlm.nih.gov/30125071/

“Dehydroepiandrosterone (DHEA) and Its Sulfate (DHEA-S) in Mammalian Reproduction: Known Roles and Novel Paradigms:” https://pubmed.ncbi.nlm.nih.gov/30029728/

“Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR):” https://pubmed.ncbi.nlm.nih.gov/21586137/

“Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction:” https://pubmed.ncbi.nlm.nih.gov/26608695/

“Dehydroepiandrosterone treatment in women with poor ovarian response undergoing IVF or ICSI: a systematic review and meta-analysis:” https://pubmed.ncbi.nlm.nih.gov/27094195/

“The role of dehydroepiandrosterone in improving in vitro fertilization outcome in patients with DOR/POR: a systematic review and meta-analysis:” https://pubmed.ncbi.nlm.nih.gov/35996249/

“The Role of Resveratrol in Mammalian Reproduction:” https://pubmed.ncbi.nlm.nih.gov/33027994/

“Roles of Resveratrol in Improving the Quality of Postovulatory Aging Oocytes In Vitro:” https://pubmed.ncbi.nlm.nih.gov/31547622/

“Effects of dietary resveratrol supplementation on egg production and antioxidant status:” https://pubmed.ncbi.nlm.nih.gov/20460666/

“Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET:” https://pubmed.ncbi.nlm.nih.gov/29245250/

“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:” https://pubmed.ncbi.nlm.nih.gov/30919036/

“Quercetin delays postovulatory aging of mouse oocytes by regulating SIRT expression and MPF activity:” https://pubmed.ncbi.nlm.nih.gov/28418847/

“Quercetin supplemented diet improves follicular development, oocyte quality, and reduces ovarian apoptosis in rabbits during summer heat stress:” https://pubmed.ncbi.nlm.nih.gov/28532829/

“Quercetin promotes in vitro maturation of oocytes from humans and aged mice:” https://pubmed.ncbi.nlm.nih.gov/33177495/