Fixing your Fertility— The Answer Could Be Vitamin A

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How Modern Fertility Treatments Ignore Basic Biology

In 1924, Dr. Carl Hartman at the University of Texas pub­lished a paper regarding his ongoing research on the embry­ology of the opossum.¹ During the first few years of his research, the opossums’ diet consisted of skim milk, bread, tal­low and lean meat. Then, between 1916 and 1917, “the problem of cheap feeding was solved by [Hartman’s lab] by securing slaughterhouse offal, such as ‘lights’ (lungs), heart, liver, and tripe.” With the change of feed, Hartman’s opossum colony began to reproduce efficiently, growing to some two hundred fifty animals, and all previously noted eye pathologies resolved.

In his 1924 paper, he commented about a type of sterility that at the time was noted in female animals kept in cages for several years, characterized by atresia of the ovarian follicles (a degeneration that prevents ovulation). In these sterile females, Hartman reported, estrus cycles either disappeared or became greatly prolonged and “abnormal in their manifestations.” Research colleagues H.M. Evans and K.S. Bishop suggested to Hartman a possible connection between the caged animals’ diets and sterility—as they had, according to Hartman, “discov­ered a type of sterility in the rat referable to a deficiency of vitamin A—too light to affect the weight and general health of the animal but yet sufficient to cause an upset in the oestrous cycle. Biology was thus given a most ‘delicate’ indicator of vitamin-A.” Subsequent animal studies revealed that deficiencies of the fat-soluble vitamins, and in particular, vitamin A, led to fetal death, prolonged gestation and difficult parturition (delivery).

My personal discovery of Dr. Hartman’s novel evidence for a “delicate indicator” of early vitamin A deficiency—that is, the interruption of normal reproductive functioning in the fe­male—was extremely exciting to me, especially since it aligns with my own clinical experience. Women who come to me with problems getting pregnant often exhibit one or more of the clinical signs of vitamin A insufficiency,² and/or their diets are extremely low in preformed vitamin A (also known as retinol). Furthering my suspi­cions of inadequate vitamin A nutriture, these women often report vaginal dryness and lack of fertile cervical mucus. To my knowledge, these two uniquely female problems have not been recognized as possible signs of vitamin A deficiency in humans, even though scientists have consistently observed these reproductive problems in rats put on diets devoid of vitamin A. Dryness, caused by a “cornification” or hard­ening of the mucus-secreting vaginal epithelium (surface cells) was reported as an early mani­festation of vitamin A deficiency by multiple groups of researchers.³ But just as vitamin A was shown to be highly effective against measles, this discovery—and its relevance for human reproduction—was thwarted by the arrival of modern medicine with its patented drugs and profitable procedures.

VITAMIN A DEFICIENCY ATTRACTS INTEREST

Beginning in the late 1980s, renewed inter­est in vitamin A led to an explosion of studies reaffirming its versatility.⁴ We now know that more than five hundred genes are regulated by vitamin A, many of which control embryonic and fetal development.⁵ Acknowledged by ex­perts to be one of its most critically important roles, successful childbearing requires pre­formed vitamin A at each developmental stage, from preconception and pregnancy through lactation and postnatal development. Vitamin A is “crucial for maintaining pregnancy and morphogenesis of developing organs and tis­sues.”⁶ (Morphogenesis is “the shaping of an organism by embryological processes of dif­ferentiation of cells, tissues, and organs and the development of organ systems according to the genetic ‘blueprint.’”⁷) Scientists have vastly expanded upon early discoveries made in the 1930s, when they conducted dietary depriva­tion studies on animals to see what happens to developing embryos when individual vitamins are removed from the maternal diet. What they discovered was that vitamin deficiencies—and, most dramatically, deficiencies of vitamin A— were a reliable way of producing congenital malformations in the embryo.

Researchers demonstrated that a wide range of embryonic defects occur in the vitamin A-deficient embryos of pigs, sheep, cattle, rabbits, rats and humans. The list included defects to the brain and central nervous system, eyes, face, teeth, ears, limbs, kidneys, genitals, skin, lungs and heart, and, in severe deficiency, complete fetal resorption.^8,9 In human infants born to mothers with lower levels of vitamin A (even in the absence of a frank deficiency), also documented were increased incidence of severe vision problems, heart defects, orofacial defects, delayed growth and impaired lung function.¹⁰ Further investigations determined that these defects are caused by the down-regulation of genes (occurring with a shortfall of vitamin A) that tightly control the changing anatomy of the embryo.

Subsequently, researchers found that vitamin A produced a similar spectrum of abnormalities when provided in excess dur ing the gestational period. However, these animal feeding experiments were done using vitamin A metabolites, in particular the most biologically active form, retinoic acid, supplied in large excess to pregnant animals. Several of these same abnormalities were then seen in human babies when their mothers inadvertently took a synthetic form of vitamin A, Accutane (13-cis-retinoic acid), during pregnancy.⁸ (The mechanism of action by which excessive vi­tamin A exerts teratogenicity is attributed to the influence of high concentrations of certain retinoic acid metabolites, such as trans-retinoic acid and 13-cis-retinoic acid, on the function of genes during critical periods of organogenesis and embryogenesis.¹¹) The focus on the neces­sity of vitamin A began to shift to a concern that pregnant women could be at risk of getting too much.

A RECKLESS RECOMMENDATION

The study that eventually led to striking preformed vitamin A from the list of nutrients reproductive clinicians consider essential to proper fetal development was published in 1995 by Rothman and colleagues in the highly influential New England Journal of Medicine. Rothman warned against intakes of preformed vitamin A, or retinol, that exceeded 10,000 IU per day from supplements or a total of 15,000 IU per day from diet and supplements, linking these levels to neural crest birth defects.¹² To ensure a margin of safety, the researchers urged women to avoid taking supplements that exceeded 4,000 to 8,000 IU daily (the range in typical prenatal multivitamins at that time) and further sug­gested that even without supplements, women consuming liver frequently could exceed safe intakes of vitamin A.¹³

Chris Masterjohn, PhD, has critiqued this study for its several weaknesses in methodol­ogy.¹⁴ Nevertheless, as a result of the Rothman study, expectant mothers have been warned not to consume liver—the most excellent source of preformed vitamin A. Not unexpectedly, 65 percent of prenatal vitamins now contain no preformed vitamin A (identified on the label as retinyl, retinyl palmitate, or retinyl acetate) and instead only contain beta-carotene, essen­tially a “provitamin A” or vitamin A precursor that has little utility for people with genetic polymorphisms and other causes of low conversion of carotenoids to retinol.¹⁵ Prenatal vitamins that do contain retinol/ retinyl provide daily doses from a very low 500 IU to 4,300 IU.¹⁰ In the last few years, more prenatal vitamins with the retinol form of vitamin A have come onto the market, which is an encouraging response to the unintended consequences of the Rothman study.

Additional research has further exposed the recklessness of the widespread warnings against consuming any amount of retinol during pregnancy (including from liver) that arose following the Rothman study. In a 2022 review article on “evidenced-based recommendations for an optimal prenatal supplement,”10 the authors cited two studies that found that pregnant women in the U.S. are more likely to be deficient in vitamin A than their non-pregnant counterparts, even after supplementation. One of these studies found that 33 percent of the unsupplemented pregnant women were vitamin A deficient as compared to 17 percent of those who supplemented with 4,000 to 6,000 IU of preformed vitamin A; neither group was low in beta-carotene.¹⁶ The second study found that the lowest quartile of maternal dietary intake of vitamin A was associated with a 3.4 times higher risk of a serious heart defect in the baby.¹⁷

For women whose diets are low in preformed vitamin A, I concur with the conclusion of these review authors, who stated: “Overall, these studies suggest that higher levels of supplementation of vitamin A, but not carotenoids, are needed during pregnancy.” They continued, “Vita­min A levels decrease during pregnancy, the average intake is below the RDA, and 2500 IU (750 mcg)/day of retinol was insufficient for women in the US to increase levels to that of non-pregnant US women. There­fore, higher levels of retinol are needed [italics added]. Beta-carotene or mixed carotenoids may also be helpful, but are insufficient even at normal levels to normalize levels of retinol” [the physiologically essential form of vitamin A measured in the serum].

Unfortunately, widespread misinformation persists about the need for preformed vitamin A before, during and after pregnancy, and only 13 percent of prenatal supplements meet or exceed the review authors’ recommendation for preformed vitamin A. Furthermore, there seems to be almost no recognition by the medical community that vitamin A is instrumental to fertility in women and men.

I have discussed the exaggerated fear of preformed vitamin A dur­ing pregnancy previously.¹⁸ What is important to understand, is that the traditional pattern of consuming animal liver (one to two servings per week) has never been linked to a single case of birth defects. (In the lit­erature, “only one case of congenital abnormalities has been reported [in 1986] that was associated with high liver consumption”; the authors who flagged the 1986 study note that evidence about vitamin A intake during early pregnancy often is “anecdotal” and “poorly documented.”¹⁹) In ad­dition, the window where an excessive intake of retinol has the potential to cause birth defects is within the first eight weeks of pregnancy.²⁰ This does pose a challenge for licensed practitioners like myself when treating women who are actively trying to conceive and have indications of a pre existing vitamin A deficiency. As their nutrition improves, they could become pregnant at any time and, therefore, as a licensed practitioner, I can only suggest a total intake of preformed vitamin A from foods and/or supplements that is well within the guidelines published by the So­ciety for Birth Defects Research and Prevention, which (along with other mainstream medical organizations) used to advise, “Supplementation of 8,000 IU vitamin A (as retinol/retinyl esters) per day should be considered the recommended maximum prior to or during pregnancy until further evaluations can be performed in the human population. . . Most prenatal vitamin preparations contain 8,000 IU/capsule of vita­min A as a daily supplement.”²¹

Fortunately, my experience has shown that for women who choose not to eat liver, amounts of retinol between 2,500 and 6,000 IU from supplements along with a diet rich in pastured eggs and full-fat dairy will replete most women (and their male partners) in just one to three months’ time, and they successfully conceive. In the third trimester, I suggest that a woman con­sume slightly higher amounts of vitamin A— between 6,000 and 10,000 IU—to provide for herself and her baby and prepare for lactation. This is somewhat lower than both the Weston A. Price Foundation guidelines of 20,000 IU per day before, during and after pregnancy, and the 25,000 IU daily recommendations of two influ­ential nutritionists and authors, the late Carlton Fredericks and Adelle Davis.^22,23 Interestingly, when lactating mice were supplemented with the human equivalent of 20,000 IU of retinol, no signs or symptoms of vitamin A toxicity were observed in the offspring.²⁴

To my knowledge, there is only one pub­lished case report of a woman who was given a large dose of retinol—100,000 IU intramuscu­larly—just two weeks before she learned that she was pregnant.²⁵ Her ophthalmologist, un­aware that she was concurrently seeking fertility treatment, diagnosed her with a corneal problem caused by a severe vitamin A deficiency due to gastrointestinal malabsorption, along with a B₁₂ deficiency, and treated her accordingly. Consult­ing obstetricians suggested allowing the woman to carry to term, and at twenty-eight weeks, the anatomy scan was normal. The twenty-eight-year-old had been diagnosed with secondary infertility after delivering two babies within the previous four years. No cause was identified by the infertility clinic—her periods were regular and progesterone levels suggested she was ovu­lating, but she did have a polycystic appearance to her ovaries. This is a pattern I see in many of my patients who have been unsuccessful in conceiving or maintaining a pregnancy after one or more successful pregnancies, especially when they are closely spaced.

Of note, these authors remark, “This is a rare case of established vitamin A deficiency related to secondary infertility”; they add that “there are no reported cases in the literature to suggest management of cases with vitamin A deficiency and infertility.” In this “rare case,” secondary infertility was quickly solved in about a month after restoration of vitamin A levels; however, B₁₂ repletion may have played a role as well. My practice experience indicates that this is not a rare occurrence. On the con­trary, multiple pregnancies, especially if fol­lowed by lactation, put a woman at much higher risk for vitamin A deficiency. Because I employ a total nutrition approach, none of my cases solely involve repleting vitamin A to restore fertility, but it is clear to me that it is one of the most significant dietary factors—if not the most significant. The lead author of the case report is an IVF (in vitro fertilization) specialist whose primary interest is the clinical management of couples with fertility problems²⁶; he and his case report co-authors wisely suggest, “if a woman with vitamin A deficiency is seeking pregnancy, it seems a better solution to have. . . vitamin A levels replenished and then starting active attempts to become pregnant” (italics added).

In my patients’ and my own experience, the vast majority of OB-GYNs simply advise women trying to conceive to “eat healthy,” “lose weight if obese” and “take any prenatal vitamin that contains folic acid.” This guidance does not typically change even when a woman has gone a year or more without success. (Many fertility doctors are now recommending various supple­ments, but with the exception of Iva Keene, ND, I have yet to see any recommend a source of preformed vitamin A, either in my patients or on their websites.)

Contrast this absence of vitamin A to the policy statement of the American Academy of Pediatrics (AAP), which identifies vitamin A among the dozen key nutrients that support neurodevelopment in the first one thousand days of life, starting from the moment of conception. The AAP urges women and their children to get referred to nutrition support during this crucial time and posits, “Understanding the complex interplay of micro- and macronutrients and neurodevelopment is key to moving beyond simply recommending a ‘good diet’ to optimiz­ing nutrient delivery for the developing child.”²⁷

Unfortunately, fertility doctors and even OB-GYNs are often completely uneducated on the foods and nutrients required for successful reproduction. When they do give their patients advice, it is limited at best and dismissive or harmful at worst. Pediatricians also lack aware­ness of the importance of the complete array of essential nutrients, often only considering vitamin D or iron to be of concern. In my own profession, the contingent of dietitians who are educated on the principles of traditional diets is relatively small. (One notable example is Lily Nichols, RD, author of Real Food for Pregnan­cy.) The majority of dietitians guide parents and parents-to-be on the benefits of eating a more “plant-based” diet and choosing lean proteins.

ASSISTED REPRODUCTION: A GLOBAL INDUSTRY

For couples experiencing fertility chal­lenges, there exists a myriad of conventional medical and alternative providers, as well as websites, social media, books, videos and courses providing treatment or guidance on improving the chances of conceiving. One of the most popular strategies is to seek the care of a fertility specialist who is licensed to deliver as­sisted reproduction technologies (ART), which can include prescribing drugs, performing intrauterine insemination, and, if needed, per­forming the most invasive treatment of all: IVF.

ART treatments, including IVF, are a global industry, bringing in sixteen billion U.S. dollars worldwide in 2021 and growing at an annual rate of 10 percent.²⁸ The term “reproscape” has been coined to describe this booming business. Each year in the United States, more than fifty-five thousand women give birth to a baby conceived through ART. Twelve percent of American women fifteen to forty-four years old—over seven million of them—have received medical care for infertility.²⁹ In the U.S., the average cost of one IVF cycle is over twenty thousand dollars,³⁰ plus the cost of expensive medica­tions; each cycle has a success rate of about one in three for women under age thirty-five and steadily decreases with age to less than 2 percent for women over age forty-four. Many women go through multiple cycles of IVF,²⁸ and in the majority of states, insurance either does not pay or caps payments, leaving couples with large medical expenses. Worldwide, there are over six thousand assisted reproduction clinics; India has the highest number of clinics overall, while Israel has the highest number per capita. In some countries, the number of children con­ceived via IVF is as high as 6 percent.³¹

Perhaps even more alarming is that babies conceived through IVF are at higher risk for congenital problems, including cardiac, mus­culoskeletal and genitourinary malformations. There is also an increased risk of respiratory, blood-related and brain abnormalities if fro­zen embryos are used, and higher risks for pre-eclampsia for the mothers.²⁹ The risks for preterm birth and low birth weight are over 50 percent higher than in non-IVF pregnancies. Swiss physicians hypothesize that in addition to maternal and paternal factors, causes of these problems may include the IVF technol­ogy itself.³¹ In addition, I hypothesize that the increased risks are in part due to the probable inadequate nutritional status of the parents, which may have prevented them from conceiv­ing naturally in the first place.

The Swiss medical doctors have gone on the record, warning, “For the well-being of the children to be conceived, IVF therapy should only be carried out in cases of infertility that cannot be treated by any other means, as the precise causes of the risks of IVF to child health are unclear” [italics added].³¹ But can infertility be treated by “other means” in these seemingly difficult cases? If so, what are the problems that health care providers should be trying to solve? What means should they utilize? And perhaps the biggest question of all is one that I will leave the reader to ponder: Does it align with the self-interest of the reproductive industry for health care providers to work to solve these problems?

Restorative reproductive medicine (RRM) is an alternative medical approach to help couples conceive without ART. The interven­tions include educating couples on fertility awareness methodologies, providing treatment for metabolic and immune diagnoses and cor­recting levels of hormones, including thyroid, progesterone and androgens, as appropriate.³² It also encourages improved nutrition, using targeted nutritional interventions as a first-line therapy.

WHAT’S BEHIND DECLINING FERTILITY?

The global fertility rate declined by nearly 1 percent per year from 1960 to 2018. This equates to more than 10 percent per decade and more than 50 percent over fifty years. In just forty years, sperm counts have fallen by 50 percent as well.³³ In the U.S., up to 15 percent of couples currently are infertile.³⁴ Globally, as reported by the World Health Organization in 2023, one in six people will be affected by infertility in their lifetime, up from the prior estimate of one in eight.³⁵ When I meet with a woman experiencing what I refer to as “subfertility,” she often shares that she feels alone—but clearly, she is far from alone. Unfortunately, many women take on self-blame, especially if their partners’ semen analysis comes back “normal.”

A woman is diagnosed with infertility when she fails to get pregnant after twelve months of targeted unprotected intercourse, or after six months if she is over thirty-five years of age. Experts consider the occur­rence of multiple miscarriages (medically termed “recurrent pregnancy loss” and defined by the spontaneous loss of two or more pregnancies) to be distinct from the diagnosis of infertility. Infertility is thought to depend on female factors in anywhere from 20 to 70 percent of cases, on male factors in about 30 to 50 percent of cases, and on both male and female factors in 40 percent of cases.³⁶ The most common known causes of female and male infertility are listed in Table 1.³⁷

TABLE 1. Leading Causes of Female and Male Infertility

FEMALE CAUSES
• Egg quality (measured by antral follicle count, embryo genetic testing)
• Ovulatory disorders (polycystic ovary syndrome, thyroid disease, undereating or overexercising, premature ovarian failure, or, more rarely, tumors)
• Uterine or cervical abnormalities (such as polyps, fibroids, abnormal shape of uterus)
• Damaged or blocked fallopian tubes
• Endometriosis
• Pelvic scar tissue
• Insufficient cervical mucus
• Short luteal phase
• Insufficient progesterone production

MALE CAUSES
• Abnormal sperm production or quality—number or function (measured by count, motility, morphology and genetic defects)
• Exposure to toxic chemicals, radiation, or prescription or non-prescription drugs, including chemotherapy
• Frequent exposure of testicles to heat

Note that while some causes are readily identifiable, they are not always easy to resolve with conventional medical treatments. For both fe­male and male infertility, conventional medicine—in contrast to nutrition and other holistic therapies—can offer no treatment to improve overall egg quality and sperm quality. The best that doctors can do is to force the ovaries to produce more mature eggs with medications like letrozole, select the most viable sperm for IVF with a technique called intracyto­plasmic sperm injection (ICSI) and, after fertilization is achieved outside the body, select the most viable embryos to “implant” into a woman’s uterus. Implantation is a very complicated process and may be the most difficult problem to overcome, even if all else goes according to plan.

The known causes of infertility listed in Table 1 do not include the 30 percent of infertility cases that doctors diagnose as “unexplained” because they cannot identify a cause. In 2015, the editor-in-chief of the Journal of Reproduction & Infertility wrote:

“The veracity of ‘unexplained infertility’ term has been challenged by many clini­cians and researchers; they emphasize that the assignment of this title to an infertile couple is much dependent on the quantity, quality and nature of the applied diagnostic tests. [. . . ] Our inability to find the causes of couples’ infertility does not mean that there is no cause for the disorder. Extensive research should be conducted on other pos­sible causes of failed conception such as ovarian and testicular dysfunctions, sperm and oocyte quality, fallopian transport de­fects, endometrial receptivity, implantation failures, and endometriosis.”³⁸

Moreover, while the issues listed in Table 1 may appear to be root causes, in my experience (and that of other holistically oriented profes­sionals), clearly, they often are not. For example, there is growing recognition of the detrimental effects of environmental toxins and synthetic chemicals on both female and male fertility.33 Multiple scientists and authors are now warning women and men to limit exposure to toxins like BPA, phthalates and PFAS (per- and polyflu­orakyl substances); even the CDC website lists published research on BPA and implantation failure in women undergoing IVF.³⁹

Undernutrition and specifically micronutri­ent deficiencies can adversely affect the outcome of every maternal and fetal stage—preconcep­tion, conception, implantation, placental de­velopment and embryo/organogenesis. Studies have linked vitamin and mineral deficiencies to “significantly high reproductive risks, ranging from infertility to fetal defects and long-term diseases.”⁴⁰ Unfortunately for couples undergo­ing ART, a 2022 systematic literature review concluded that “findings. . . do not support any single dietary pattern for the purpose of im­proving pregnancy or live birth rates in women undergoing IVF treatment.”⁴¹ This recent review claiming to encompass the “breadth of the scientific evidence” probably explains in part why ART doctors do not refer their patients to qualified nutritionists like myself. (If I were to be more suspicious, I would guess that these MDs may prefer that couples don’t find success outside of their revenue stream.)

Fortunately, the popular media are now drawing attention to a poor-quality diet as a strong contributing factor to fertility struggles, along with deficiencies in nutrients such as vi­tamin D and folate. As a result, many couples wanting to optimize their chances of successful ART/IVF are seeking dietary guidance. How­ever, as the couples who meet with me dem­onstrate, it is the “Wild West” out there when it comes to trying to decipher which dietary information is most accurate. Couples are bom­barded with messaging to eat a low-saturated-fat, plant-based diet to optimize fertility,⁴² yet Dr. Price’s research shows that this is exactly the wrong approach. One notable exception to the bad advice is the somewhat well-known recommendation for full-fat dairy from the Harvard School of Public Health, which found that the consumption of more than five servings of lowfat dairy foods per week increased the risk of anovulatory infertility, whereas high-fat dairy foods reduced the risk.^43,44 The researchers hypothesized that the presence of a fat-soluble substance in the high-fat dairy improves ovar­ian function.

We know that dairy fat is an excellent source of both vitamin K2 and vitamin A, es­pecially if it is from animals on pasture, and it likely provides other less understood but im­portant nutrients as well. We also know that the animal-sourced foods containing the fat-soluble vitamins—A, D, E and K2—are instrumental for health and especially for healthy reproduc­tive function. Dr. Price captured all the nutrition guidance we need in his studies of indigenous populations thriving on their traditional diets.⁴⁵ These populations did not know about vitamins as we now understand them but, when plan­ning to have children, they knew that “sacred foods” rich in critical nutrients were important. Regarding vitamin A, according to Sally Fallon Morell and Mary Enig, “[Dr. Price’s] research demonstrated that generous amounts of vitamin A ensure healthy reproduction and offspring with attractive wide faces, straight teeth and strong sturdy bodies”; in addition, Price noted, “the foods held sacred by the peoples he studied, such as spring butter, fish eggs and shark liver, were exceptionally rich in vitamin A.”⁴⁶

Today, couples who follow a nourishing Wise Traditions diet report having healthy babies even into their forties, despite their doc­tors labeling them as “geriatric pregnancies” because of their “advanced maternal age.”⁴⁷ They also understand the importance of proper pregnancy spacing, which avoids the known risks of adverse outcomes due to maternal deple­tion of nutrients.⁴⁰

VITAMIN A MECHANISMS ENABLING AND GOVERNING REPRODUCTION

As stated earlier, vitamin A affects just about every function in the body, so it is not sur­prising that it also exerts multiple effects on both female and male reproductive function. Early re­search revealed the basic necessity of vitamin A for reproduction and showed what can go wrong morphologically if it is deficient, depending on the timing and extent of deficiency. Subsequent research has revealed what is happening at the biochemical level. Vitamin A (through its physiologically active form, all-trans retinoic acid) is now considered a hormone due to the hormonal-like signaling of its specific nuclear receptors, which govern gene transcription. For this reason, tissue levels of retinoic acid are tightly regulated but ultimately are dependent on the supply, uptake, transport and storage of its vitamin A precursors.⁴⁸ A 2020 report explains, “In contrast to classical hormones, there is no endocrine gland that synthesizes retinoids, con­trolled via feedback by the hypothalamus and pituitary gland. Instead, the levels of the active form of vitamin A (all-trans retinoic acid; RA) are tightly regulated via local cellular enzymatic mechanisms; a regulation that is critical for correct signaling via the nuclear receptors.”⁴⁸

In the female, evidence indicates that vitamin A plays a role in the multiple stages of reproduction: hypothalamic-pituitary axis hormone secretion, ovarian steroid hormone synthesis and secretion, ovary development, selection of dominant follicles, oocyte matu­ration, fertilization, formation of the corpus lutea, blastocyst (fertilized egg) implantation, fetal development and parturition. Vitamin A is required for the proper functioning of the ovaries, fallopian tubes, uterus and vaginal epithelium. In animals that are vitamin A-deficient, ovarian weight is significantly reduced over animals sufficient in vitamin A, providing further evidence that the reproductive function of the female is heavily dependent on vi­tamin A (p. 547).⁴⁹ A 2011 study identifies retinoic acid as a top activin-regulated pathway, with activin playing an important role in the synthesis and secretion of follicle-stimulating hormone (FSH).⁵⁰

Studies have shown that low serum levels of retinol (and vitamin E) are associated with anovulation (failure of the ovaries to release an egg during the menstrual cycle) in women and abnormal sperm parameters in men.⁵¹

From studies in animals, scientists have learned that the impact of vitamin A deficiency on reproductive outcomes depends both on the degree of the deficiency and when the deficiency occurs.⁵² When severe vitamin A deficiency is present prior to mating, females typically fail to enter estrous and ovulate. Vitamin A appears to be required for the selec­tion of a dominant follicle via the hormone-dependent differentiation of a mature egg and release at ovulation. In animals that are sufficient in vitamin A, high concentrations of vitamin A have been detected in fol­licular fluid and much higher concentrations in developing follicles than in atretic (degenerating) follicles (p. 551).⁴⁹ In a study published in 2016, researchers observed that when they fed mice a retinol-deficient diet for three weeks, the mice ovulated fewer cumulus-oocyte complexes, and the oocytes within the ovulated complexes exhibited impaired development.⁵³ (The cumulus-oocyte complex “is ovulated during the ovulatory phase of the menstrual cycle and is just what it seems: an oocyte surrounded by specialized granulosa cells, called cumulus cells. The cumulus cells sur­rounding the oocyte ensure healthy oocyte and embryo development.”⁵⁴) Three weeks for mice equates to twenty-eight months for humans, so it is easy to see how quickly a diet low in vitamin A can impair a woman’s fertility, especially if she has depleted her body’s stores from the demands of one or more previous pregnancies and lactation(s).

In less severe vitamin A deficiency, ovulation may occur, but the oocytes (eggs) are likely to degenerate in the fallopian tubes. One or both fallopian tubes may also become cornified, resulting in a malfunction of the tubal cilia (little “hairs” that create “waves” of propulsion), which, along with a reduced quantity and quality of the mucus secretions, can prevent the sperm from effectively interacting with the egg. Traveling into the tubes requires that the sperm already have penetrated the uterine cavity, which becomes unlikely if the amount or quality of cervical mucus is compromised from lack of vitamin A. Lastly, the cornified reproductive tissues can prevent the implantation of the fertilized egg.⁵⁵

With mild vitamin A deficiency, fertilization and implantation occur, but the embryo will likely be resorbed or die early in gestation. This is not unexpected, given that the early phases of normal gestation (in vitamin A-sufficient animals) are marked by a high concentration of vitamin A accumulation in the conceptus (the embryo in the uterus). This could reflect a mechanism that prepares the conceptus to meet the presumably higher vitamin A requirements of the critical period of organ differentia tion.⁵⁶ Vitamin A is also needed for proper development of the placenta; even a mild vitamin A deficiency can lead to the death of the placenta, resulting in fetal loss. Vitamin A is necessary for the synthesis of pro­gesterone by the corpus luteum (formed from the follicle after releasing the egg), followed by the placenta after the first trimester of pregnancy. Progesterone is essential to sustaining pregnancy. Many women with a history of miscarriages and low progesterone levels are now given pre­scription progesterone in the first trimester to support pregnancy; I have seen appropriate preconception supplementation with vitamin A to be as effective in many cases.

For a woman desiring pregnancy, there are also potential problems that vitamin A repletion will not be able to address. Consider that vita­min A is required during the initial stages of egg development (meiosis) that occur while a female fetus is developing in utero; this suggests the possibility that if a pregnant woman has insufficient vitamin A intake or levels, her daughter could be at risk for fewer viable eggs over her own reproductive lifespan.⁵²

A second problem involves Müllerian anomalies, which affect about 4 percent of women. Considered a congenital disorder, they can result in malformations (present at birth) to the fallopian tubes, uterus and other reproductive tissues.⁵⁷ When pregnant rats are fed a diet deficient in vitamin A, their fetuses exhibit incomplete Müllerian duct develop­ment, suggesting that vitamin A signaling is essential for this duct’s development.⁵⁸

Finally, surviving offspring of animals mildly deficient in vitamin A display a variety of abnormalities that can affect just about every organ. These include congenital diaphragmatic hernia (a congenital anomaly that is on the rise59), skeletal defects and, notably, “a less developed nasal region.”⁶⁰ This mirrors Dr. Price’s findings that proper facial and skeletal development in children is critically dependent on the mother ingesting sufficient quantities of all the fat-soluble vitamins during the gestational period.⁶¹ Congenital diaphragmatic hernia remains the most life-threatening cause of severe respiratory failure in the term infant. Its incidence is one in twenty-five hundred births,⁶² and it accounts for about 8 percent of major congenital anomalies.

Vitamin A may support IVF success for couples who choose that option. A study of fifty women undergoing IVF had three important findings.⁶³ First, serum and follicular fluid levels of fat-soluble vitamins were very highly correlated. Second, the mean follicular fluid (FF) concentration of vitamin A was associated with a higher mean day two and day five (post-fertilization) embryo quality status. Third, higher FF vitamin A levels (along with vitamin E levels) predicted the fertilization success of each individual egg. Both vitamin A and vitamin E act as FF antioxidants that protect against excessive reactive oxygen species, which can cause damage to DNA and cell membranes, affecting the de­velopment of both the eggs and embryos. Conversely, this study found a negative correlation between serum vitamin D levels and the mean day five embryo score and no correlation with fertilization success. From this study, one can conclude that supplementing vitamin D without attention to adequate vitamin A intake—a typical protocol I have seen ART doc­tors use—is inadvisable.

Because a handful of studies indicate benefit for IVF outcomes, some ART doctors recommend nutraceuticals such as CoQ10, inositol, acai berry and melatonin, with the stated goal of reducing damaging levels of reac­tive oxygen species and improving egg health. However, according to Chris Masterjohn, PhD, vitamin A is a superior antioxidant for both egg and sperm membranes. It also has a spar­ing effect on glutathione—the most important endogenous antioxidant—which is also crucial for fertility.^64,65

It will likely be some time before true vita­min A is no longer considered a risk factor for birth defects but correctly recognized as a “criti­cal determinant in reproductive outcome that can lead to either a complete failure of repro­duction prior to implantation or fetal resorption or malformation.”52 Interestingly, a September 2023 conference sponsored by FACTS about Fertility and the Institute of Restorative Re­productive Medicine of America is featuring a keynote presentation on the “Role of Vitamins A & D in Optimizing Sex Hormone Function, Pregnancy, and Breastfeeding.”⁶⁶

VITAMIN A AVOIDANCE

Why don’t health care practitioners recom­mend sources of vitamin A to infertile couples? Modern medicine follows evidenced-based, quantitative protocols derived from peer-reviewed published studies. A group of scientists succinctly described the problem where vitamin A is concerned: “Convincing results in humans [as to teratogenicity in humans], which would allow clear-cut recommendations to females for the safe use of vitamin A [during pregnancy], are lacking.”⁶⁷ Because none currently exist for vitamin A during the periconception period, and a couple of influential peer-reviewed studies suggest harm,¹² it is no surprise that most health care practitioners choose to avoid the issue, especially since they blindly trust the formula­tions of any and all prenatal vitamins to correct nutrient shortfalls. As one group of researchers describes it, vitamin A supplementation during pregnancy is “a controversial issue [that] holds a lot of paradoxical facts.”⁶⁸

There are five prevailing but erroneous beliefs about vitamin A. The first is that women should avoid the retinol form of vitamin A “as it can cause birth defects”; this belief is com­pounded by the lack of understanding that the converse is actually true: inadequate vitamin A intake can cause birth defects. Note that as late as 2005, the U.S. Food and Drug Administra­tion (FDA) published a suggested daily value of 8,000 IU for supplements labeled for pregnant and lactating women; prior to that, I recall that prenatal vitamins generally supplied 5,000 IU in the retinyl ester form. Currently, a few provide 4,000 to 4,300 IU of a retinyl ester such as reti­nyl palmitate. In any case, studies indicate that it is only before the eighth week of gestation, while embryogenesis is still occurring, that excessive preformed vitamin A from supplements (greater than 10,000 IU) has been purportedly linked to fetal malformations.⁶⁹

The second prevailing belief among di­etitians and other health care providers is that there is a low population risk of vitamin A deficiency in developed nations and that it is only in low-income countries that vitamin A deficiency during pregnancy is common.^70,71 For example, the prominent clinical education site StatPearls states that in the U.S. general population, “vitamin A deficiency is rare, esti­mated at 0.3% in 2013” and that “the prevalence of vitamin A toxicity. . . is much greater than deficiency.”² The view is that most diets contain sufficient amounts of vitamin A and that the most fat-soluble forms, retinyl esters, can be stored within the body in relatively high levels, thereby counteracting periods of low dietary intake.⁴⁸ Current nutrition textbooks, too, state that vitamin A deficiency is rarer in the U.S. than in developing countries, with the excep­tion of children under five, considered the pre­dominant age group suffering from inadequate vitamin A intake.⁷² However, the 2007–2010 NHANES studies in the U.S. contradict this belief, indicating that 51 percent of U.S. adults consume less than 621 mcg (or 2,068 IU) from their diets,⁷³ and that amount includes the often poorly utilized carotenoid forms. (One textbook author points out that carotenoids are embedded within plant cells and that cooking or extensive mechanical chewing is necessary to break down the digestion-resistant plant cell walls.⁷²) Likewise, in the UK, 30 percent of women between nineteen and thirty-four years of age have reported vitamin A intakes below the recommended lower limit.⁷⁴ Vitamin A deficiency is considered a public health concern if 15 percent or more of the population has a plasma retinol concentration of less than 0.7 micromoles/liter,⁶⁹ but because testing of serum levels is limited in the U.S., the actual prevalence most certainly is unknown. Unfortunately, the concern for excessive vitamin A intake far exceeds any concern for inadequate intake, especially in pregnant women, even though studies have found that many women are deficient in vitamin A immediately after delivery,⁷⁵ placing them at higher risk for anemia and potentially lactation failure, and putting their babies at even higher risk for early childhood vitamin A deficiency.

Third, the upper limit of 10,000 IU per day for preformed vitamin A is not intended to apply to malnourished people or as a way to avert a vitamin A defect,^76,77 yet a prevailing issue is that health care provid­ers are not likely to try to correct a vitamin A deficiency in a woman trying to conceive.

Fourth, there is a belief that carotenoids (the plant forms of provi­tamin A) supply adequate vitamin A for the majority of the population, regardless of stage of life or pre-existing condition.

Liver is the best dietary source of vitamin A, but the fifth prevailing belief is that liver is unhealthy due to storing toxins and has too much vitamin A to recommend when a woman is pregnant. The UK National Health Service specifically lists liver as a food to avoid when pregnant.⁷⁸ Sadly, most younger women will not eat liver, as they did not eat it grow­ing up, and they tell me that they cannot tolerate the taste. For those women, I suggest they try desiccated liver capsules.

MY APPROACH: COUPLES WHO WANT TO START A FAMILY

Since 2016, I have focused my practice on women’s reproductive health, combining traditional dietary principles with my clinical ex­perience, training and ongoing literature reviews. I am experienced in interpreting the signs, symptoms and risk factors of nutrient shortfalls— this is one of the most important tools I use to help patients regain their health and reproductive functioning. Many of the shortfalls I uncover are fairly common in my patients: vitamins B₆, B₁₂, E, and D, magnesium, calcium, iodine, selenium, zinc, iron, glycine and choline. However, the most common and notable problem, hands down—occurring in at least two-thirds of my female patients who have cycling or fertility problems—is low vitamin A status.

What is even more remarkable is that many of these female patients appear to have had a long-standing vitamin A insufficiency—some for several years. You might suppose that I know this because my patients provide me with blood test results indicating that their vitamin A levels fall below the reference range, yet only a few patients have had a vita­min A blood test. In contrast, the vast majority have had one or more vitamin D blood tests. I would note that while blood testing is helpful in some cases, diagnosing vitamin A deficiency may require more than the signs of deficiency are easy to miss if you aren’t trained to look for them.⁷⁹

I believe that doctors’ failure to screen for and treat “subclinical” vitamin A deficiency is one of the most critical yet completely unrec­ognized gaps in the conventional health care system. For couples wanting to have healthy children, it is a modern-day tragedy. Even more unfortunate is the compromised health of the children born to parents who are vitamin A-insufficient for one reason or another (see sidebar, page 25). As mentioned, the increased health risks faced by children born through IVF may, in part, be attributable to unaddressed low vitamin A status (and other nutrient shortfalls) of the mothers during pregnancy and continuing during the breastfeeding period.

What signs of vitamin A deficiency do I see that doctors tend to overlook?

• Skin problems: Hyperkeratosis (mainly as hardened follicular “bumps” on the back of the arms); sometimes acne, eczema and/or dandruff; and very often, chronically dry skin.
• One or more eye problems: Reduced dim-light vision (often first noticed as increased sensitivity to glare, which can impede night driving); dry eyes; intolerance to sunlight.
• Frequent respiratory infections, allergies, asthma, hard-to-treat anemia, low energy levels in spite of taking thyroid medication and, in many cases, low output of fertile cervical mucus, irregular menstrual cycles, anovulatory cycles and low progesterone levels.

The natural progression of chronic vita­min A deficiency most commonly leads to the gradual development of night blindness; increased frequency of gastrointestinal, pulmo­nary and urinary infections; and development of xeroderma and phrynoderma (follicular hy­perkeratosis often found on extensor surfaces, shoulders and buttocks).²

Most of these patients are taking poor-qual­ity prenatal vitamins that supply only vitamin A in the form of hard-to-convert beta-carotene— or sometimes supply no vitamin A at all. None are eating liver, taking cod liver oil or eating abundant amounts of pastured eggs or full-fat dairy. Many have European ancestry, which means they are much more likely to have one or more of the common genetic polymorphisms that reduce the conversion of carotenoids to retinol, the physiologically essential form of vi­tamin A. Upon inclusion of an adequate amount of preformed vitamin A in the diet, resolution of these symptoms can be seen in as little as one to two months, with vision improvements being among the earliest to occur. (For more details, see my other articles in Wise Traditions, “Vi­tamin A: The Scarlet Nutrient”¹⁸ and “Vitamin A-mazing,”⁸⁰ as well as other information about vitamin A on the WAPF website.⁸¹)

What results do I see when a woman who is having reproductive problems makes the recommended changes to ensure she is fully nourished in all nutrients, with special atten­tion to vitamin A? Over two-thirds experience the restoration of regular ovulatory menstrual cycles; for those desiring pregnancy, over half realize natural conception, which results in a full-term pregnancy (without complications) and a healthy baby. For others who choose or need to undergo IVF, their doctors are surprised by their outcomes, which include a much greater number of high-quality embryos, followed by a successful transfer and pregnancy. Initial prog­ress can occur in as little as two to three months.

Some patients are lost to follow-up, so I may not be seeing the full effects of these nutritional improvements over time, but the majority send me photos of their beautiful babies and share ap­preciation for my guidance, stating that it made all the difference. One woman, in particular, stands out. She had had three failed IVF cycles. Six months after our first appointment, she re­peated the egg harvest and fertilization process and obtained eleven high-quality embryos; be­fore, she had obtained four of uncertain quality. She was able to get pregnant from the transfer of one of these embryos and has had a normal pregnancy thus far. To what did her ART doctor attribute this remarkable improvement? He told her, “We did a really good protocol.” My patient insisted, however, that the IVF protocol was the same and told me it was her nutrition that made the difference.

I am convinced that the human body, when provided with the right nourishment, will function as it was designed for the vast majority of people. Women who have been told they are infertile are no exception.

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SIDEBARS

VITAMIN A VOCABULARY: RETINOL, RETINAL AND RETINOIC ACID
Dietary retinol is converted to retinal and then to retinoic acid, which acts in the nucleus of our cells to govern genetic transcription. Transcription can be thought of as the process of putting genes into action with the synthesis of specific proteins being the ultimate target.

Because retinoic acid controls the action of our genes, its levels are tightly controlled in the body. Retinol and retinyl esters (the forms of vitamin A found in animal foods) are not the active forms for gene regulation; rather, they enter circulation after a meal and then in large part are shuttled to the liver for storage. As it is needed, the liver releases retinol, carried on a transport protein called retinol binding protein; this complex circulates in the blood to be taken up by receptors on the cells of our tissues and organs and then converted into retinoic acid.

WHY ARE SO MANY WOMEN DEFICIENT IN VITAMIN A? EIGHT REASONS FEW OR NO SACRED FOODS EATEN:

Due to erroneous messaging that sacred foods like organ meats (especially liver), deep-orange poultry eggs or fish eggs and pastured dairy are to be avoided, intake of these foods is often low or nonexistent. When women do consume eggs or dairy, the foods often come from animals that lack access to pasture, so these animals’ intake of carotenoids (which the animals can efficiently convert to retinol) is low.

LOST TRADITION OF CONSUMING HIGH-VITAMIN COD LIVER OIL: This tradition has been largely replaced by fish oils to supply DHA during pregnancy. In addition, many cod liver oils have vitamin A removed or reduced.

PREVALENT PROBLEM OF LOW INTAKES: In the U.S., according to NHANES data, four out of five women have vitamin A intakes below the U.S. RDA of 700 to 770 mcg (~2,300 to 2,500 IU). In the Netherlands, a study found that women who did not consume liver or liver products had average vitamin A intakes below the recommended daily amounts (with the recommended amounts generally equating to 2,665 IU and 3,300 IU for non-pregnant and pregnant Dutch women, respectively, which is higher than the U.S. RDA).¹⁹ About 70 percent of the women who consumed no liver had vitamin A intakes below the RDA.

RELIANCE ON BETA-CAROTENE: Preformed vitamin A (retinol) is efficiently absorbed (70 to 90 percent), but the absorption of beta-carotene appears to be highly variable (5 to 65 percent), depending on food- and diet-related factors and the individual’s age and health status.⁵ This can be compounded by poor conversion of beta-carotene to retinol, due to common (but typically undetected) genetic characteristics prevalent in individuals of European ancestry, or pre-existing disease states such as hypothyroidism and heavy metal toxicity, or co-existing deficiencies in nutrients such as zinc and iron. The prevalence of hypothyroidism is estimated at 2 to 4 percent in women of reproductive age and is likely higher due to subclinical or undiagnosed cases. In women with diagnosed infertility, the prevalence is over 20 percent.⁸²

ZINC DEFICIENCY: This can lead to an apparent vitamin A deficiency even in the presence of seemingly adequate vitamin A intake. Zinc is required for both the absorption and conversion of beta-carotene to retinol. The subsequent conversion of retinol to the more active retinoic acid requires sufficient zinc levels within the cells lining the gut. Zinc is required for the retinol binding protein that transports stored vitamin A from the liver to the tissues of the body; retinol-binding protein is also the most important transporter of vitamin A to the fetus from the mother.⁶ Conversely, there is also evidence that adequate vitamin A governs zinc absorption and utilization.⁸³ Zinc deficiency is much more likely with high intake of plant foods (especially grains, legumes and nuts) that not only do not provide adequate zinc but are high in phytates that significantly block zinc absorption. Soils have become very depleted in zinc, which translates to lower zinc in the crops grown on them.

EXCESSIVE SUPPLEMENTATION WITH VITAMIN D: This becomes a problem when dosed for more than a few months, as it leads to the enhanced utilization of vitamin A, effectively depleting it even further.⁸⁴ Obstetricians and fertility specialists are now quite aware that many women have low vitamin D status, and some will treat it with an ongoing dose of 4,000 IU or more per day.

OBESITY: Obesity appears to cause a “silent” vitamin A deficiency,⁸⁵ marked by reductions in vitamin A levels in the liver and signaling in multiple organs. Even with adequate intake from the diet, there is a drastic reduction in vitamin A concentrations and an impaired ability to use vitamin A correctly. With weight loss, vitamin A levels and signaling normalize. This could partially explain why weight loss, for some, does improve fertility.

EXCESSIVE INTAKE OF VEGETABLE OILS HIGH IN POLYUNSATURATED OMEGA-6 FATTY ACIDS: According to Martin Grootveld, PhD, industrial oils introduce toxic by-products into the body, notably toxic aldehydes and lipid peroxides, which cause widespread oxidative stress and create cellular-level deficiencies of critical micronutrients, including vitamins A, B₁, B₆, B₉ and zinc along with glutathione. Consumption of commercial fried foods is a principal dietary culprit,⁸⁶ but obesity and environmental toxins (such as lead, smoking) are also risk factors. Oxidative stress results from an imbalance of reactive oxygen species (ROS) to antioxidants. Low ROS levels have a regulatory role in oocyte maturation, while excessive levels are implicated in the pathology of infertility in both women and men. Sperm are extremely sensitive to attack by ROS, with a limited capacity to repair ROS-induced DNA damage. Retinol and vitamin E are natural antioxidants that inhibit lipid peroxidation and protect against cellular/gamete damage. Serum levels of malondialdehyde, another toxic by-product of oxidized fatty acids, are twice as high in women with anovulatory cycles compared to those who ovulate.⁵¹ I believe that at least half of the women I work with who have been diagnosed with polycystic ovary syndrome (PCOS) actually don’t have PCOS. I suspect poor diets and obesity create high levels of ROS; studies of women with PCOS show ROS levels to be higher. These women are easy to help, but it takes some time to get destructive fatty acids out of the body. Vitamins A and E can help as chain-breaking antioxidants. As Dr. Chris Knobbe explained in Wise Traditions (Summer 2023), the modern diet filled with excessive omega-6 oils underlies the majority of chronic diseases, even when the oils are not subjected to frying temperatures.⁸⁷

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REFERENCES

1. Hartman C. Vitamin-A and exercise in relation to follicular atresia in the opossum. Am J Physiology. 1924;68:91-102.
2. Hodge C, Taylor C. Vitamin A deficiency. Treasure Island (FL): StatPearls Publish­ing; 2023 Jan-.
3. Sherwood TC, Brend MA, Roper EA. Changes in the vaginal epithelium of the rat on an excessive vitamin A diet. The Journal of Nutrition. 1936;11(6):593-597.
4. Wiseman EM, Bar-El Dadon S, Reifen R. The vicious cycle of vitamin A deficiency: a review. Crit Rev Food Sci Nutr. 2017;22;57(17):3703-3714.
5. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environ­ment. First draft statement on the effects of excess vitamin A on maternal health. 2021. TOX/2021/57. https://cot.food.gov.uk/sites/default/files/2021-11/TOX-2021-57%20Vitamin%20A%20istatement%20Updated_0.pdf
6. Quadro L, Hamberger L, Gottesman ME, et al. Pathways of vitamin A delivery to the embryo: insights from a new tunable model of embryonic vitamin A deficiency. Endocrinology. 2005;146(10):4479-4490.
7. https://www.britannica.com/science/morphogenesis
8. Maden M. Vitamin A and the developing embryo. Postgraduate Med J. 2001;77(910):489-491.
9. Kalter H, Warkany J. Experimental production of congenital malformations in mammals by metabolic procedure. Physiol Rev. 1959;39(1):69-115.
10. Adams JB, Kirby JK., Sorensen JC, et al. Evidence based recommendations for an optimal prenatal supplement for women in the US: vitamins and related nutrients. Matern Health Neonatol Perinatol. 2022;8(1):4.
11. Tzimas G, Nau H. The role of metabolism and toxicokinetics in retinoid teratogen­esis. Curr Pharm Des. 2001;7(9):803–831.
12. Rothman KJ, Moore LL, Singer MR, et al. Teratogenicity of high vitamin A intake. New Engl J Med. 1995;333(21):1369-1373.
13. Brody J. Study links excess vitamin A and birth defects. The New York Times, Oct. 7, 1995.
14. Masterjohn C. Vitamins for fetal development: conception to birth. Wise Traditions. Winter 2007;8(4):24-35.
15. Haskell MJ. The challenge to reach nutritional adequacy for vitamin A: β-carotene bioavailability and conversion—evidence in humans. Am J Clin Nutr. 2012;96(5):1193S-1203S.
16. Baker H, Frank O, Thomson AD, et al. Vitamin profile of 174 mothers and newborns at parturition. Am J Clin Nutr. 1975;28(1):59-65.
17. Shaw GM, Carmichael SL, Yang W, et al. Periconceptional nutrient intakes and risks of conotruncal heart defects. Birth Defects Res A Clin Mol Teratol. 2010;88(3):144- 151.
18. Schoenfeld P. Vitamin A: the scarlet nutrient. Wise Traditions. Summer 2016;17(2):18- 28.
19. Van den Berg H, Hulshof KFAM, Deslypere JP. Evaluation of the effect of the use of vitamin supplements on vitamin A intake among (potentially) pregnant women in relation to the consumption of liver and liver products. Eur J Obstet Gynecol Reprod Biol. 1996;66(1):17-21. Citing Rosa FW, Wilk AL, Kelsey FO. Teratogen update: vitamin A congeners. Teratology. 1986;33(3):355-364.
20. Masterjohn C. Concerns about vitamin A in preg­nancy: Masterjohn Q&A files episode 37. Harnessing the Power of Nutrients, Substack, Jan. 2, 2020.
21. Society for Birth Defects Research and Prevention. Teratology Society position paper: recommendations for vitamin A use during pregnancy. Teratology. 1987;35(2):269-275.
22. Fredericks C. Carlton Fredericks’ Guide to Women’s Nutrition: Dietary Advice for Women of All Ages. Tracy, CA: Perigee Trade, 1989.
23. Davis A. Let’s Have Healthy Children. New York: Harcourt, Brace & World, Inc., 1959.
24. Tan L, Zhang Y, Crowe-White KM, et al. Vitamin A supplementation during suckling and postwean­ing periods attenuates the adverse metabolic effects of matenal high-fat diet consumption in Sprague-Dawley rats. Curr Dev Nutr. 2020;4(8):nzaa111.
25. Kalampokas T, Shetty A, Maheswari A. Vitamin A deficiency and female fertility problems: a case report and mini review of the literature. J Womens Health Care. 2014;3:317.
26. https://www.researchgate.net/profile/Theodoros-Kalampokas
27. Schwarzenberg SJ, Georgieff MK, Committee on Nutrition, et al. Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health. Pediatrics. 2018;141(2):e20173716.
28. Global fertility treatments market research report 2021: Market is expected to reach $21.7 billion in 2025 at a CAGR of 8% – Long-term forecast to 2030 – ResearchAndMarkets.com. Business Wire, Jan. 25, 2022.
29. Dusenbery M. What we don’t know about I.V.F. The New York Times, Apr. 16, 2020 (updated Nov. 9, 2021).
30. Katkin E. Conceivability: What I Learned Explor­ing the Frontiers of Fertility. New York: Simon and Schuster, 2018.
31. Von Wolff M, Haaf T. In vitro fertilization technology and child health. Dtsch Arztebl Int. 2020;117(3):23-30.
32. Boyle PC, Stanford JB, Zecevic I. Successful preg­nancy with restorative reproductive medicine after 16 years of infertility, three recurrent miscarriages, and eight unsuccessful embryo transfers with in vitro fertilization/intracytoplasmic sperm injection: a case report. J Med Case Rep. 2022;16(1):246.
33. Swan SH, Colino S. Reproductive problems in both men and women are rising at an alarming rate. Sci­entific American, Mar. 16, 2021.
34. https://www.uclahealth.org/medical-services/obgyn/conditions-treated/infertility
35. 1 in 6 people globally affected by infertility: WHO, Apr. 4, 2023. https://www.who.int/news/item/04-04-2023-1-in-6-people-globally-affected-by-inferti­lity#:~:text=Around%2017.5%25%20of%20the%20adult,care%20for%20those%20in%20need
36. Mazzilli R, Cimadomo D, Vaiarelli A, et al. Ef­fect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. Fertil Steril. 2017;108(6): 961–972.e3.
37. Mayo Clinic staff. Infertility. Mayo Clinic, Sep. 1, 2021. https://www.mayoclinic.org/diseases-conditions/infertility/symptoms-causes/syc-20354317
38. Sadeghi MR. Unexplained infertility, the controversial matter in management of infertile couples. J Reprod Infertil. 2015;16(1):1-2.
39. Ehrlich S, Williams PL, Missmer SA, et al. Urinary bisphenol A concentrations and implantation failure among women undergoing in vitro fertilization. Environ Health Perspect. 2012;120(7):978-983.
40. Cetin I, Berti C, Calabrese S. Role of micronutrients in the periconceptional period. Hum Reprod Update. 2010;16(1):80-95.
41. Sanderman EA, Willis SK, Wise LA. Female dietary patterns and outcomes of in vitro fertilization (IVF): a systematic literature review. Nutr J. 2022;21(1):5.
42. Eagleson H. What’s the best fertility diet when trying to get pregnant? Parents, updated Jul. 7, 2023.
43. Chavarro JE, Rich-Edwards JW, Rosner B, et al. A prospective study of dairy foods intake and anovulatory infertility. Hum Reprod. 2007;22(5):1340-1347.
44. Eating ice cream may help women to conceive, but low-fat dairy foods may increase infertility risk. ScienceDaily, Feb. 28, 2007.
45. Price WA. Nutrition and Physical Degeneration, 6th edition. La Mesa, CA: Price- Pottenger Nutrition Foundation, 2004 (originally published 1939).
46. Fallon S, Enig MG. Vitamin A saga. Wise Traditions. Winter 2001;2(4). https://www.westonaprice.org/health-topics/abcs-of-nutrition/vitamin-a-saga/
47. Wagner A. Geriatric moms? [Letter] Wise Traditions. Spring 2023;24(1):4.
48. Nilsson C. Retinoids in Mammalian Reproduction, with an Initial Scoping Effort to Identify Regulatory Methods. Nordic Council of Ministers, TemaNord 2020:507. https://pub.norden.org/temanord2020-507/#
49. Blomhoff R (Ed.). Vitamin A in Health and Disease. NY: Marcel Dekker, 1994.
50. Kipp JL, Golebiowski A, Rodriguez G, et al. Gene expression profiling reveals CYP26b1 to be an activin regulated gene involved in ovarian granulosa cell prolif­eration. Endocrinology. 2011:152(1):303-312.
51. Al-Azemi MK, Omu AE, Fatinikun T, et al. Factors contributing to gender dif­ferences in serum retinol and alpha-tocopherol in infertile couples. Repro Biomed Online. 2009;19(4):583-590.
52. Clagett-Dame M, Knutson D. Vitamin A in reproduction and development. Nutrients. 2011;3(4):385-428.
53. Kawai T, Yanaka N, Richards JS, et al. De novo-synthesized retinoic acid in ovarian antral follicles enhances FSH-mediated ovarian follicular cell differentiation and female fertility. Endocrinology. 2016;157(5): 2160-2172.
54. https://www.repropedia.org/cumulus-oocyte-complex
55. https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/cervical-mucus
56. Takahashi YI, Smith JE, Goodman DS. Vitamin A and retinol-binding protein metabolism during fetal development in the rat. Am J Physiol. 1977;233(4):E263- E272.
57. https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/mullerian-anomalies
58. Jiang Y, Chen L, Taylor RN, et al. Physiological and pathological implications of retinoid action in the endometrium. J Endocrinol. 2018;236(3):R169-R188.
59. Nichols L. Liver and organ meat: nutritional benefits & how to make it palatable. Lily Nichols RDN, n.d. https://lilynicholsrdn.com/liver-organ-meat/
60. Medeiros DM, Wildman REC. Advanced Human Nutrition, 4th edition. Burlington, MA: Jones and Barlett Learning, 2019.
61. Morell SF. Nutrition and Physical Degeneration by Weston A. Price [book review]. Weston A. Price Foundation, Jan. 1, 2000.
62. https://cdhi.org/cdh-statistics/
63. Skowrońska P, Kunicki M, Pastuszek E, et al. Follicular fat-soluble vitamins as markers of oocyte competency. Syst Biol Reprod Med. 2020;66(2):112-121.
64. Cha JH, Yu QM, Seo JS. Vitamin A supplementation modifies the antioxidant system in rats. Nutr Res Pract. 2016;10(1):26-32.
65. Oyewopo A, Johnson O, Adeleke O, et al. Review on the role of glutathione on oxidative stress and infertility. JBRA Assist Reprod. 2018;22(1):61-66.
66. https://www.factsaboutfertility.org/revitalizing-womens-health/
67. Miller RK, Hendrickx AG, Mills JL, et al. Periconceptional vitamin A use: how much is teratogenic? Reprod Toxicol. 1998:12(1):75-88.
68. Youness RA, Dawoud A, ElTahtawy O, et al. Fat-soluble vitamins: updated review of their role and orchestration in human nutrition throughout life cycle with sex differences. Nutr Metab (Lond). 2022;19(1):60.
69. Heimburger DC, McLaren DS, Shils ME. Clinical manifestations of micronutrient deficiencies and toxicities: a resume. In ME Shils et al. (Eds.), Modern Nutrition in Health and Disease, 10th edition. Baltimore, MD: Lippincottt Williams & Wilkins, 2006, pp. 595-612.
70. Thorne-Lyman AL, Fawzi WW. Vitamin A and ca­rotenoids during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2012;26 Suppl 1(0 1):36-54.
71. Searles K. CPE Monthly: Eye health and nutrition. Today’s Dietitian. January 2023;25(1):40.
72. Allen JC. Advanced Nutrition and Metabolism: What is the Quest? , 2nd edition. Ronkonkoma, NY: Linus Learning Publishers, 2017.
73. Drake VJ. Micronutrient inadequacies in the US population: an overview. Corvallis, OR: Linus Paul­ing Institute, Oregon State University, November 2017.
74. Grune T, Lietz G, Palou A, et al. Beta-carotene is an important vitamin A source for humans. J Nutr. 2010;140(12):2268S-2285S.
75. Corrine Hanson, Elizabeth Lyden, Chad Abresch, Ann Anderson-Berry, Serum Retinol Concentra­tions, Race, and Socioeconomic Status in of Women of Childbearing Age in the United States. Nutrients 2016 Aug 19;8(8):508.
76. Munoz N, Bernstein M. Nutrition Assessment, Clinical and Research Applications. Burlington, MA; Jones & Bartlett Learning, 2019.
77. Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington DC; National Academies Press, 2001.
78. https://www.nhs.uk/pregnancy/keeping-well/foods-to-avoid/
79. Masterjohn C. How to manage your vitamin A status | Chris Masterjohn Lite #60. https://www.youtube.com/watch?v=tZY0OCBNwtw
80. Schoenfeld P. Vitamin A-mazing. Wise Traditions. Spring 2020;21(1);13-26.
81. https://www.westonaprice.org/abcs-of-nutrition/
82. Verma I, Sood R, Juneja S, et al. Prevalence of hy­pothyroidism in infertile women and evaluation of response of treatment for hypothyroidism on infertil­ity. Int J Appl Basic Med Res. 2012;2(1):17-19.
83. Christian P, West KP Jr. Interactions between zinc and vitamin A: an update. Am J Clin Nutr. 1998;68(2 Suppl):435S-441S.
84. Masterjohn C. Beyond good and evil: synergy and context with dietary nutrients. Wise Traditions. Fall 2012;13(3):15-26.
85. Trasino SE, Tang XH, Jessurun J, et al. Obesity leads to tissue, but not serum vitamin A deficiency. Sci Rep. 2015;5:15893.
86. Moumtaz S, Percival BC, Parmar D, . . . Grootveld M. Toxic aldehyde generation in and food uptake from culinary oils during frying practices: perioxidative resistance of a monounsaturate-rich algae oil. Sci Rep. 2019;9(1):4125.
87. Knobbe C. The omega-6 apocalypse. Wise Traditions. Summer 2023;24(2):14-23.

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