PDF Summary:It Starts with the Egg, by Rebecca Fett

If you're struggling with infertility, miscarriage, or reduced egg quality, you may be able to improve your chances of conception by making specific dietary and lifestyle changes. In It Starts with the Egg, Rebecca Fett explains how egg quality is influenced by factors like mitochondrial function, oxidative stress, and exposure to environmental toxins—and how you can address these factors in the months before conception.

Fett outlines the science behind egg development and chromosomal abnormalities, then provides guidance on reducing exposure to toxins like BPA and phthalates, following a fertility-supporting diet, and using targeted supplements. She also addresses underlying conditions like PCOS, endometriosis, thyroid disorders, and gluten intolerance that may be affecting your fertility. This guide offers specific supplement protocols based on your individual fertility challenges.

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It also raises the likelihood of successful IVF. Foods in a Mediterranean diet contain certain vitamins and fatty acids linked to reduced inflammation and better fertility. These include vitamin B6, vitamin B12, and folic acid, which lower the amount of the harmful amino acid homocysteine. Elevated homocysteine is connected to an increased risk of miscarriage. The Mediterranean diet also highlights oils and fats with anti-inflammatory properties, especially those present in seafood, nuts, and olive oil. The author says these fats may help with fertility, whereas saturated fats are probably harmful. Omega-3 fatty acids help with inflammation, aid in producing progesterone, and increase blood circulation to the uterine area. Olive oil is high in antioxidants like vitamin E and includes oleic acid, a kind of monounsaturated fat, which is key to egg development.

The Case for Animal Fats

In Real Food for Mother and Baby, Nina Planck argues that traditional diets high in animal fats, including saturated fat, can be compatible with and even beneficial for fertility. She contends that saturated fat and cholesterol are needed to make sex hormones, and that animal fats are rich in fat-soluble vitamins A, D, and K2 that support regular ovulation, implantation, and the building of a healthy placenta and baby. Planck points to traditional diets of healthy populations that included plenty of animal fats, and she argues that a diet that skimps on these old-fashioned fats can quietly weaken fertility rather than protect it. She recommends butter, cream, egg yolks, liver, and other organ meats from pastured animals as among the most valuable foods for women who want to conceive.

Fett also notes that elevated insulin and blood sugar can harm fertility by interfering with the hormonal equilibrium that regulates the reproductive system. Elevated insulin can negatively impact ovulation by disrupting the hormonal balance of the ovaries. Elevated blood glucose and insulin can also impair mitochondrial function, which is critical for developing eggs. This can lead to chromosomal abnormalities, issues with embryo development, and unsuccessful implantation. Elevated levels of glucose and insulin can also heighten the likelihood of miscarriage.

To stabilize glucose and insulin, Fett recommends decreasing your total carbs and selecting more unprocessed, natural foods.

When Decreasing Carbs May Not Be Helpful

While Fett’s advice to stabilize glucose and insulin by decreasing your total carbs and selecting more unprocessed, natural foods may be helpful for some women, it may not be helpful for women whose infertility is not driven by elevated insulin and blood sugar. For example, medical researchers note that women who have functional hypothalamic amenorrhea (FHA) due to low energy intake and heavy exercise may experience worsened ovulation and fertility if they decrease their total carbs. FHA is a condition where the hypothalamus, a part of the brain that regulates hormones, reduces or stops the release of hormones that control the menstrual cycle. This can lead to irregular or absent periods and can impact fertility. FHA is often caused by factors such as excessive exercise, significant weight loss, or stress, which signal to the body that it is not an optimal time for reproduction.

Targeted Use of Supplements and Healthcare Considerations

Fett recommends considering targeted supplementation to address specific reproductive challenges. For example, those with unidentified fertility issues often have weakened antioxidant defenses in their ovarian follicles, and taking antioxidant supplements may decrease how long it takes to become pregnant. PCOS affects fertility by interfering with ovulation and lowering the quality of eggs, while endometriosis impacts fertility through oxidative stress and inflammation that harm egg development. Additionally, chromosomal errors in the egg cause almost 50% of early miscarriages, and improving egg quality may reduce the chance of these errors.

(Shortform note: While antioxidant supplements may improve egg quality, researchers caution that excessive antioxidant use could disrupt the delicate balance of oxidative processes necessary for normal reproductive function. A research article explains that while oxidative stress can damage eggs, some level of oxidation is essential for processes like ovulation and embryo implantation. Over-supplementation could potentially suppress these necessary oxidative signals, paradoxically impairing fertility rather than enhancing it. This highlights the importance of consulting a healthcare professional before starting any supplement regimen, especially when trying to conceive.)

Fett provides several suggestions for supplementation: - If you're struggling to conceive and haven't yet started treatments like IUI or IVF, incorporate some foundational supplements, prioritizing antioxidants. Consider incorporating a prenatal multivitamin with a minimum of 800 mcg of methylfolate or folate from food sources, as well as 400 mg of ubiquinol daily, 500 mg of vitamin C, and 200 IU of vitamin E. You might include alpha-lipoic acid or N-acetylcysteine to enhance antioxidant effects. Consult your physician about checking for deficiencies in vitamin D, gluten intolerance, and hypothyroidism. If your vitamin D is lower than the recommended threshold of 40 ng/ml or 100 nmol/L, you could take 4000–5000 IU of vitamin D3 each day. In cases of substantial deficiency, consider starting with a daily dosage of 10,000 IU for two weeks.

(Shortform note: While supplements can be beneficial, they can also be dangerous if you have certain health conditions. For example, medical researchers published an academic paper describing a case of vitamin D toxicity in a woman with sarcoidosis, a granulomatous disease. The patient developed hypercalcemia (elevated calcium levels in the blood) after taking 4,000 IU of vitamin D3 daily for three months, followed by 10,000 IU daily for two weeks. The researchers explained that granulomatous diseases like sarcoidosis can increase the risk of vitamin D toxicity because they cause immune cells to produce excess active vitamin D, leading to elevated calcium levels. The researchers emphasized the importance of monitoring vitamin D levels and calcium levels in patients with granulomatous diseases who are taking vitamin D supplements.)

• If you have PCOS, you might try using these supplements for two or three months before attempting to conceive: a prenatal vitamin with 800 mcg of methylfolate or folate from natural foods, myo-inositol (4 g daily), ubiquinol (400 mg per day), R-alpha lipoic acid (200 mg), N-acetylcysteine (600 mg), L-carnitine (3 g per day), and melatonin (3 mg at bedtime). - If you have endometriosis, you may want to take a prenatal vitamin containing a minimum of 800 mcg of folate from natural food sources or methylfolate, 400 mg daily of CoQ10 in the form of Bio-Quinon or ubiquinol, and R-alpha lipoic acid (300 mg).

(Shortform note: If you have PCOS or endometriosis and are already following the standard of care for these conditions, you may not need to take all of the supplements Fett recommends. For example, if you have PCOS and are already taking medications to regulate your menstrual cycle, reduce androgen levels, and manage insulin resistance, you may not need to take all of the supplements Fett recommends. Similarly, if you have endometriosis and are already taking medications to manage pain and inflammation, and have had surgery to remove endometrial tissue, you may not need to take all of the supplements Fett recommends.)

• If you've experienced repeated pregnancy loss, consider taking these supplements for a three-month period before attempting conception again: a prenatal that includes a minimum of 800 mcg of methylfolate, 400 mg per day of CoQ10 (either as ubiquinol or Bio-Quinon), R-alpha lipoic acid (200–300 mg), vitamin E (200 IU), N-acetylcysteine (600 mg), and, if you're insulin resistant, myo-inositol (4 g daily). If you're pursuing conception via IVF, think about incorporating melatonin supplements (3 mg at night, starting 14 days to a month before egg retrieval).

(Shortform note: This supplement regimen may not be relevant if your repeated pregnancy loss is due to a structural issue with your uterus. For example, a septate uterus, which is a congenital condition where a band of tissue divides the uterine cavity, can significantly increase the risk of miscarriage. In this case, the primary issue is the physical barrier within the uterus, not necessarily the quality of the eggs or the uterine environment. While supplements may still support overall reproductive health, they won't address the underlying anatomical problem.)

Talk to a doctor about checking for hypothyroidism, a primary factor in repeat miscarriages. You might want to be checked for celiac disease, especially if you show any signs or have relatives with celiac or other autoimmune issues. Get your vitamin D level checked, and think about taking 4000–5000 IU of vitamin D3 daily if you're under the ideal target level (at a minimum of 40 ng/ml or 100 nmol/L; some people think aiming higher helps manage inflammation). If you're substantially deficient, you may begin with a daily intake of 10,000 IU for a fortnight. Think about getting tests for DHEA-S and testosterone, especially if age could play a role or if your AMH or follicle count is low. Taking DHEA might boost the quantity of eggs that mature correctly every month and could help avert certain chromosomal errors leading to miscarriage.

(Shortform note: In addition to the tests Fett recommends, clinical experts in reproductive medicine recommend testing for antiphospholipid antibodies. Antiphospholipid syndrome is a common cause of repeat miscarriages, and it can be treated with blood thinners. Antiphospholipid syndrome is an autoimmune disorder that causes the immune system to attack certain proteins in the blood, leading to an increased risk of blood clots. These clots can form in the placenta, disrupting the flow of nutrients and oxygen to the developing fetus and resulting in miscarriage. The syndrome is diagnosed through blood tests that detect the presence of antiphospholipid antibodies, such as lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2 glycoprotein I antibodies. Clinical guideline authors recommend testing for antiphospholipid antibodies in women who have experienced two or more miscarriages, as early detection and treatment can significantly improve pregnancy outcomes. Treatment typically involves the use of blood thinners, such as low-dose aspirin and heparin, to reduce the risk of clot formation and support a healthy pregnancy.)

Ensure that your male partner is also using a daily multivitamin with methylfolate, a CoQ10 supplement (a minimum of 200 mg of ubiquinol or Bio-Quinon), and the advanced sperm quality supplements covered in chapter 14. - If you've been diagnosed with diminished ovarian reserve or age-related infertility, or need to pursue IVF or IUI for some other reason (such as endometriosis), think about taking these supplements for two or three months leading up to your next IVF cycle: a prenatal containing a minimum of 800 mcg of methylfolate or natural food folate, CoQ10 (as ubiquinol or Bio-Quinon, 400 mg daily), R-alpha lipoic acid (200–300 mg), N-acetylcysteine (600 mg), vitamin E (200 IU), and, as an optional extra, vitamin C (500 mg).

(Shortform note: While the supplements listed above are generally considered safe, medical researchers have raised concerns about the long-term safety of high-dose vitamin E supplementation. In a meta-analysis of 19 clinical trials, researchers found that high-dose vitamin E supplementation (400 IU or more per day) was associated with a small but statistically significant increase in all-cause mortality. The researchers hypothesized that excessive vitamin E intake may disrupt the balance of antioxidants in the body, potentially leading to pro-oxidant effects and increased risk of chronic diseases. While the absolute risk increase was small, the findings suggest that high-dose vitamin E supplementation may not be as harmless as previously thought. This raises questions about the safety of combining multiple potent antioxidant supplements, as recommended in some fertility protocols.)

As you get ready for IVF, take a nightly dose of 3 milligrams of melatonin, beginning 2–4 weeks prior to egg retrieval. Have an assessment of your DHEA-S and testosterone levels. If your levels aren't on the higher side of the typical level for younger women, you might want to take a DHEA supplement two to three months ahead of your next IVF cycle. Seek out micronized brands like Fertinatal, Douglas Labs, or Pure. A standard dosage is 25 milligrams, taken three times daily, though you might need a lower amount. Consult your physician about screening for an underactive thyroid, which often contributes to a reduced ovarian reserve in younger women.

(Shortform note: The short-term use of melatonin before an IVF cycle may be beneficial because it interacts with melatonin receptors in the ovarian follicles. These receptors are involved in the regulation of gene expression within the follicles, which in turn influences how the follicles respond to hormonal stimulation. By taking melatonin in the weeks leading up to egg retrieval, you may be subtly adjusting the timing and pattern of gene activity in the follicles, potentially optimizing their response to the carefully timed hormonal cues of the IVF process. This fine-tuning of gene expression could help ensure that the follicles develop in a more synchronized and efficient manner, increasing the chances of successful egg maturation and retrieval.)

Check your vitamin D levels, and if they're below the recommended target of 40 ng/ml or 100 nmol/L, you might think about taking a daily supplement of 4000–5000 IU of vitamin D3. If you're very deficient, you could begin by taking 10,000 IU daily for a fortnight. Ensure that your male partner takes a daily multivitamin with methylfolate, a CoQ10 supplement (minimum 200 mg of ubiquinol or Bio-Quinon), and the advanced sperm quality supplements mentioned in chapter 14.

(Shortform note: The Institute of Medicine (now the National Academy of Medicine) recommends a lower target of 20 ng/ml (50 nmol/L) for vitamin D levels, with a daily supplement of 600 IU for adults up to 70 years old and 800 IU for those over 70. They also set a maximum safe daily intake of 4,000 IU for adults. This is based on their findings that most people can maintain adequate vitamin D levels with these lower doses, and that higher doses may not provide additional benefits and could pose risks.)

Next, we’ll discuss targeted nutrient support and addressing underlying conditions.

Targeted Nutrient Support

Fett explains that myo-inositol can support fertility, especially in those who have PCOS or are insulin resistant. Myo-inositol is a sugar molecule that the body produces from glucose. It's also found in items like produce, nuts, and grains. It's categorized as a B vitamin (B8), although it's not an essential vitamin.

Myo-inositol is a precursor for signal transduction molecules that regulate cellular biological processes, such as egg development. It’s a widely used supplement for enhancing fertility. Studies show that myo-inositol can bring back the ability to ovulate, enhance the quality of eggs, and guard against gestational diabetes. It might enhance reproductive ability in anovulatory women. Myo-inositol is considered safe, with minimal to no adverse effects. People with conditions like schizophrenia or bipolarity should be cautious when using it, since it might worsen manic episodes.

Myo-Inositol Is Not a Vitamin

Although myo-inositol is sometimes called “vitamin B8,” researchers note that it doesn’t meet the criteria to be classified as a vitamin. A research article explains that vitamins are organic compounds that are essential for normal growth and nutrition and are required in small quantities in the diet because they cannot be synthesized by the body. Myo-inositol, while important for various cellular functions, can be synthesized by the body from glucose, and therefore does not meet the strict definition of a vitamin. The article notes that myo-inositol is sometimes referred to as “vitamin B8” in popular literature, but this is not an official designation recognized by nutrition science. The authors emphasize that while myo-inositol plays important roles in cellular signaling and metabolic processes, it is not classified as a vitamin in the traditional sense.

Addressing Underlying Conditions

Fett asserts that addressing thyroid disorders can enhance reproductive ability and reduce the likelihood of miscarriage. She explains that these disorders commonly affect women who have undiagnosed infertility, issues with ovulation, and early ovarian insufficiency—a condition that drastically reduces fertility by decreasing egg count and quality. Thyroid disorders frequently lead to miscarriage. Women with thyroid antibodies have over twice the rate of miscarriage. Thyroid antibodies are a sign that the body’s defense mechanisms are attacking the thyroid gland, the leading cause of hypothyroidism. Hypothyroidism is prevalent in people with ovulation disorders, unexplained infertility, and primary ovarian insufficiency. Thyroid conditions, even if they're mild, can greatly elevate the miscarriage risk.

(Shortform note: Thyroid disorders are also linked to depression, so treating them can improve your mental well-being. Thyroid disorders are common in people with depression. In fact, 30% of people with depression have thyroid antibodies, and 50% of people with depression have hypothyroidism. This is because thyroid hormones play a crucial role in regulating mood and cognitive function. When thyroid hormone levels are imbalanced, it can lead to symptoms such as fatigue, irritability, and difficulty concentrating, which are also common in depression. Additionally, thyroid disorders can disrupt the production of neurotransmitters like serotonin and dopamine, which are important for mood regulation. This overlap in symptoms and underlying mechanisms explains why thyroid disorders are often found in people with depression.)

In addition, females with thyroid autoimmune issues tend to have reduced DHEA hormone levels, which are vital for developing early follicles. Fett also notes that thyroid antibodies are prevalent in people who have PCOS. Those with PCOS also tend to have hormonal imbalances suggesting hypothyroidism. Fett recommends checking for thyroid problems if you've experienced pregnancy loss, PCOS, unexplained infertility, ovulation disorders, or premature ovarian failure. If you’ve been diagnosed with thyroid disease or celiac disease, it’s even more crucial to get tested for the other condition if you're experiencing infertility or miscarriage. Additionally, if you have thyroid antibodies, it's important to check your DHEA-S and testosterone levels.

(Shortform note: DHEA-S is a form of DHEA that has a sulfate group attached to it, which makes it more stable and allows it to circulate in the blood for a longer time. This form of DHEA acts as a reservoir, providing a steady supply of the hormone that the body can convert into other sex hormones, like estrogens and androgens, as needed. DHEA-S is produced mainly by the adrenal glands, but also by the ovaries and testes. It plays a role in various bodily functions, including the development of secondary sexual characteristics and the regulation of mood and energy levels. Doctors often measure DHEA-S levels to assess adrenal function and to help diagnose conditions related to hormone imbalances.)

If you've had multiple miscarriages and test positive for these or other antibodies, you might ultimately require medication that suppresses the immune system or prevents clotting to lower your risk of miscarriage. If an issue is identified, schedule a visit with a hormone specialist to get appropriate care. Seek a second opinion if your doctor doesn't understand the significance of thoroughly managing hypothyroidism connected to miscarriages and infertility. Some endocrinologists view a TSH level under 4.5 mIU/mL as within the "normal" range and unnecessary to treat, but numerous fertility experts feel that 1 mIU/mL is preferable. In addition to prescribing thyroid hormone replacement, many endocrinologists may also suggest a diet free of gluten and dairy and selenium supplements to lessen the autoimmune activity that impairs thyroid function.

(Shortform note: If you have a history of miscarriages and test positive for thyroid antibodies, you may be wondering whether to take medication that suppresses the immune system or prevents clotting, or to follow a gluten- and dairy-free diet with selenium supplements. You may also be wondering whether to aim for a TSH level of 1 mIU/mL or to stay under 4.5 mIU/mL. To make an informed decision, you should consider the strength of the evidence behind each option and how it applies to your specific situation. For example, the American Thyroid Association's 2017 guidelines recommend treating women with thyroid antibodies and a history of pregnancy loss with levothyroxine, but they also note that the evidence is weak and that the decision should be individualized.)

For women who experience miscarriage due to immune-related factors, avoiding gluten might also be beneficial. Going gluten-free significantly reduces the risk of miscarriage in women with celiac disease.

(Shortform note: While some studies suggest that gluten avoidance may reduce the risk of miscarriage in women with celiac disease, medical experts caution that the evidence supporting this approach is limited. The guideline authors note that the benefits of strict gluten exclusion for preventing immune-related pregnancy loss are not well-established, and more research is needed to determine its effectiveness.)

Fett also emphasizes that managing gluten intolerance might enhance fertility. Celiac disease is an autoimmune condition where gluten prompts the immune system to attack the body. Celiac disease can contribute to miscarriage and reproductive challenges by boosting inflammation and disrupting the body's ability to absorb folate and other vitamins. Decreased folate leads to elevated homocysteine, negatively affecting egg quality and raising the chances of miscarriage. Celiac disease may additionally create antibodies that can lead to miscarriage. Celiac is more frequently seen in instances of infertility with unknown causes. In those situations, celiac is only a factor in 5–8 percent of them. However, untreated celiac disease is linked to increased miscarriage risk in women.

(Shortform note: While medical researchers have found that celiac disease can contribute to pregnancy problems, clinical researchers have found that celiac disease is not a common cause of infertility. In a study of over 2 million women in the UK, researchers found that women with celiac disease were no more likely to have infertility than women without celiac disease. The researchers concluded that celiac disease is not a major cause of infertility in the general population. However, they noted that celiac disease may still contribute to pregnancy problems in a subset of women. This research paper was published in the British Medical Journal.)

For women who have celiac disease, not treating the condition makes pregnancy loss nearly nine times more likely compared to those who do receive treatment. Celiac disease is highly hereditary, and it often leads to the development of additional autoimmune conditions. Celiac is connected to thyroid autoimmunity. Thirty to 40 percent of individuals with celiac will also experience thyroid issues, and the condition makes it three times more likely you'll develop a thyroid disorder. If you have celiac disease, Fett recommends eliminating gluten from your diet to lower your miscarriage risk. Removing gluten enables the intestinal lining to recover and the body to regain its capacity to take in the nutrients essential for fertility. Adhering rigorously to a gluten-free eating plan can initiate the rebalancing of folate and homocysteine. Eliminating gluten can additionally aid in decreasing the immune activity that causes thyroid issues.

The Broader Context of Autoimmune Diseases

The connections between celiac disease, pregnancy loss, heredity, and thyroid issues reflect a broader medical understanding of autoimmune diseases. In Gluten Freedom, Dr. Alessio Fasano and Susie Flaherty explain that autoimmune diseases often cluster together in individuals and their families due to shared genetic and immune system factors. This clustering means that a diagnosis of one autoimmune condition, like celiac disease, can serve as a warning sign for other potential autoimmune issues, such as thyroid disorders. Fasano and Flaherty argue that clinicians should adopt a broader perspective when treating patients with celiac disease, considering the possibility of other autoimmune conditions and the need for long-term follow-up. This approach helps ensure that patients receive comprehensive care that addresses the interconnected nature of autoimmune diseases.