Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in trans fats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (ɷ-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.

Infertility—a failure to achieve pregnancy after 12 mo of unprotected and routine sexual intercourse—affects many reproductive-aged couples attempting pregnancy. It is estimated that ∼15% of couples worldwide experience difficulty becoming pregnant; however, female infertility contributes to only 35% of overall infertility cases, 20% of cases are related to both women and men, 30% involve problems only on the part of men, whereas 15% of infertility cases remain unexplained. According to the WHO, infertility may affect ∼80 million women worldwide. Female infertility is defined as infertility caused primarily by female factors, such as ovulation derangements, reduced ovarian reserve, reproductive system disorders, or chronic diseases. Primary female infertility is diagnosed in women who have never borne a child. Secondary female infertility affects women who have given birth to a live child or who experienced a miscarriage but who simultaneously are unable to establish clinical pregnancy. Key definitions are provided in Table 1. Besides physiological, age-related factors, female fertility is also affected by the conditions related to the pathophysiology of the reproductive organs and several other factors, such as the environment and lifestyle. Endometriosis, deregulated ovarian functions, tubal infections, and cervical and uterine factors constitute the most common reproductive pathologies; however, the etiology of some female infertility cases remains unknown.

TABLE 1

Definitions of essential terms according to the International Glossary on Infertility and Fertility Care, 2017

There is growing interest in lifestyle (including diet and physical activity), psychological stress, socioeconomic factors, BMI, smoking, alcohol, caffeine, and psychoactive substances in the context of fertility. Lifestyle—including caloric intake and diet composition in terms of vitamins, protein, lipids, carbohydrates, as well as the mineral content—seems to be especially vital in the context of infertility caused by endometriosis and ovulation disorders. Interestingly, the frequency and intensity of physical activity may differently affect fertility—intensive sports, influencing the hypothalamus-pituitary axis, may lead to hypothalamic amenorrhea and subsequently lead to infertility. However, moderate physical activity is recommended to improve ovarian function and fertility, especially among women with obesity or unable to handle stressful situations. Moreover, many studies are currently investigating the association between the intestinal microbiota and female fertility.

In view of the abovementioned factors, it is vital to adopt a holistic approach to infertility treatment in both women and men, including many specialists (e.g., physicians, dietitians, physiologists, physiotherapists). In our nonsystematic review, we aimed to summarize the current knowledge regarding dietary aspects in female infertility. However, due to a lack of clear outcomes and the small number of intervention studies, we could not formulate dietary recommendations for reproductive-aged women planning a pregnancy. Our paper does not address the topic of diet and male infertility, although we emphasize that it is crucial to focus on the lifestyle and dietary factors in male infertility treatment, especially with regard to sperm quality. We devoted a separate paper to this area including a wide range of both topics.

We performed a literature search of MEDLINE (PubMed) searching for terms such as the following: fertility, fertility diet, female fertility, PCOS, endometriosis, infertility, infertility treatment. Since our paper is a narrative, not a systematic review, we may not have included all studies, and we must acknowledge a certain publication bias. However, every author of this publication conducted the literature search independently.

Dietary habits and female fertility

Many researchers still investigate the influence of diet on fertility. Although there is undoubtedly an association between dietary habits and fertility, many questions remain unanswered. An individual diet, which comprises other comorbidities and lifestyle, is especially essential. In this section, we compared 2 different nutritional approaches which differently affect both female and male fertility.

The Mediterranean diet 

As current studies indicate, a diet based on the Mediterranean diet (MeD) recommendations positively affects mental and physical health. The MeD has also been associated with favorable changes in insulin resistance, metabolic disturbances, and the risk of obesity, which is crucial in the context of fertility. The MeD is characterized by a high consumption of vegetables (including pulses), fruits, olive oil, unrefined carbohydrates, low-fat dairy and poultry, oily fish, and red wine, with a low consumption of red meat and simple sugars.

In a review summarizing the main findings of a prospective cohort including 22,786 participants with a mean age of 35 y, a positive association between adherence to the MeD and fertility was suggested. Moreover, studies show that healthy dietary patterns can also increase the chances of live birth among women using assisted reproductive technology (ART). In a large cohort study by Chavarro et al. in 17,544 women planning a pregnancy or who became pregnant during the study, there was an association between adherence to the pro-fertility diet (similar to the MeD) and a lower risk of infertility caused by ovulation disorders. The pro-fertility diet was characterized by a lower consumption of trans-fatty acids (TFAs) and a higher consumption of MUFAs and plant-derived protein, and decreased consumption of animal protein, low glycemic index foods, high-fiber foods, and—interestingly—high-fat dairy. Women following the pro-fertility diet consumed more nonheme iron and more frequently, i.e., at least 3 times/wk, took multivitamins, in particular group B vitamins (e.g., folic acid), consumed more coffee and alcohol, and were more physically active.

Kermack et al. reported that supplementation of omega-3, vitamin D, and olive oil, which imitated the MeD, before in vitro fertilization did not affect the rate of embryo cleavage. The MeD correlated with RBC folate and serum vitamin B-6. Additionally, higher adherence to the MeD by couples undergoing in vitro fertilization increased the probability of pregnancy. It should be noted that a part of the MeD is moderate wine drinking and, for women, this equals 1 glass of red wine daily, although it may be quite controversial in the context of female fertility. We explain what impact alcohol consumption has on fertility later in this article. However, while the majority of research studies indicate dose-dependent relations between fertility and alcohol consumption, it should be taken into account that a number of pregnancies remain unplanned. Nonetheless, there are evidence-based recommendations to exclude alcohol from the diet of pregnant women.

The Western-style diet 

In contrast to the MeD, the Western-style diet (WsD) is rich in refined and simple carbohydrates (mostly sugar, sweets, and sweetened beverages) and red and processed meat. Moreover, it is characterized by a low intake of fresh fruits and vegetables, unrefined grains, low-fat poultry, and fish. It could also be described according to its high caloric, fat, and high glycemic index intake, with a low consumption of dietary fiber and vitamins.

According to the conducted studies, the WsD decreased IL-1RA concentrations and the cortisol-cortisone ratio in the follicular fluid, and reduced the number of blastocysts. Moreover, a higher consumption of fast food and a lower intake of fruit were associated with infertility, and with a moderate increase in the time to become pregnant. Additionally, an animal study indicated that the WsD altered ovarian cycles and affected hormone concentrations, decreasing progesterone and anti-Müllerian hormone. The study also demonstrated that the WsD increased the number of antral follicles and delayed the time to the estradiol surge.

It has been shown that a diet with a high glycemic index and rich in animal protein, TFAs, and SFAs may negatively affect fertility. These aspects will be discussed later in the paper. However, it should be noted that studies investigating the direct relation between the WsD and fertility are still necessary. A comparison between the MeD and the WsD with regard to female fertility is presented in Table 2.

TABLE 2

Characteristics of the Mediterranean and the Western-style diets, and their influence on female fertility¹

¹ART, assisted reproductive technology; IR, insulin resistance; PCOS, polycystic ovary syndrome; T2D, type 2 diabetes; TFA, trans-fatty acid.

Dietary compounds and female fertility

Both insulin sensitivity and glucose metabolism can significantly affect ovulation and female fertility. In terms of carbohydrates, glycemic index and load are especially essential. Possibly, the consumption of high glycemic index products can increase insulin resistance, dyslipidemia, and oxidative stress, which negatively affects fertility and the ovarian functions.

Insulin regulates metabolism but also reproductive functions; it can modulate ovarian steroidogenesis as well as hyperinsulinemia which are correlated positively with hyperandrogenism and ovulation disorders. Insulin is also the primary regulator of the production of sex hormone–binding globulin (SHGB) among women with polycystic ovary syndrome (PCOS). High glycemic index and load have been associated with higher fasting glucose concentrations, hyperinsulinemia, and insulin resistance, and therefore with higher concentrations of insulin-like growth factor I (IGF-I) and androgens, which can lead to endocrine disturbances and, thus, may alter the maturation of oocytes. A large cohort study conducted in 18,555 women without a history of infertility, who planned or became pregnant during the study, showed that a higher consumption of carbohydrates at the cost of naturally occurring fats and with a high glycemic index was positively associated with infertility due to ovulation disorders. These results were confirmed by other studies where the higher consumption of high glycemic index products and carbohydrates, when compared with fiber intake, and a high consumption of simple sugars were related to lower chances of becoming pregnant. The main sources of added sugars are carbonated beverages, which can negatively affect fertility. Moreover, Machtinger et al. observed that the consumption of sweetened, carbonated beverages—independently of the caffeine intake—can decrease the chances of reproductive success by means of ART. It has also been shown that the consumption of carbonated beverages is associated with increased concentrations of free estradiol.

Undoubtedly, both the amount and the type of carbohydrates are essential in the context of a pro-fertility diet among women with lipid and glucose metabolism disturbances. However, this aspect is also essential in the diet of reproductive-aged women planning to become pregnant.

Fats constitute a vital dietary compound affecting fertility. Hohos and Skaznik-Wikiel suggested that a high-fat diet can be associated with changes in the reproductive functions, including menstrual cycle length, reproductive hormone concentrations [e.g., luteinizing hormone (LH)], and embryo quality in the ART cycles.

Furthermore, it seems that the quality of fat is more important than its amount. The Chavarro et al. study comprising 18,555 women planning a pregnancy or who became pregnant during the study demonstrated that increasing the intake of TFAs by even 2% resulted in a significant increase in infertility risk due to ovulation disorders. In contrast, Mumford et al. did not observe associations between TFAs, SFAs, and the relative risk of anovulation in the BioCycle Study. It is worth bearing in mind that the Chavarro et al. study was conducted in the United States between 1991 and 1995, and the first cohort study indicating the harmfulness of TFAs appeared only in 1993. On the other hand, the BioCycle Study was conducted between 2005 and 2007, when the United States already had mandatory labeling of the TFA content in foods containing ≥0.5 g TFAs/serving. Furthermore, in another study, the negative influence of TFA intake on fertility was observed among 1290 American women planning a pregnancy. However, this association was not observed among the Danish women and, as the authors suggested, may be associated with a low consumption of TFAs among this cohort due to the 2003 Danish law requiring a limit of TFAs in fats and oils to 2% of the total fatty acids (FAs).

TFAs have proinflammatory properties and may increase insulin resistance, increasing the risk of developing type 2 diabetes or other metabolic disturbances, including PCOS, which can negatively affect fertility. It has been assumed that the direct negative effect of TFAs is associated with their influence on and a decreased expression of peroxisome proliferator–activated receptor γ (PPAR-γ). Moreover, the intake of TFAs was associated with the incidence of endometriosis. According to the Global Burden of Diseases Study, differences in TFA consumption between countries in 2010 range from 0.2% to 6.5% of energy intake, whereas the mean global TFA intake is 1.4% of the total energy intake. The highest intake of TFAs is observed in Egypt, Pakistan, Canada, Mexico, and Bahrain, although the WHO recommends limiting consumption of TFAs to 1% of total energy intake. Some countries, following the example of Denmark, have taken action to limit the amount of TFAs in food by introducing TFA limits in food or by compulsory labeling of products containing TFAs. It seems that prohibiting TFAs is the most effective approach to reduce the amount of TFAs in the food supply. In countries where there are no limits on the amount of TFAs in food, products high in TFAs can still be found in supermarkets and are often cheaper than their TFA-free counterparts. Therefore, it seems that it is necessary to continuously increase the nutritional awareness of the public, as well as to learn how to read labels in order to make proper nutritional choices.

On the other hand, ɷ-3 FAs can positively affect fertility, as they play an essential role in steroidogenesis and have significant anti-inflammatory properties. Currently, the available studies indicate that ɷ-3 FAs from oily fish or supplements have a beneficial effect on the growth and maturation of oocytes, decrease the risk of anovulation, and improve embryo morphology, and are associated with higher concentrations of progesterone. However, the results of the association between ɷ-3 FAs and fertility are contradictory. In numerous studies, no association, or insufficient evidence, has been observed. It seems, however, that ɷ-3 FAs—by increasing insulin sensitivity and improving the lipid profile—may be helpful in the treatment of PCOS, although more studies are required. The supplementation of ɷ-3 FAs decreases follicle-stimulating hormone (FSH) among women with normal weight, which has not been observed in women with obesity. On the basis of this study, it is possible to suggest that ɷ-3 FAs extend the reproductive lifespan. Nevertheless, further investigations among women with a diminished ovarian reserve are critical. Nassan et al. demonstrated that the consumption of fish, which is a good source of ɷ-3 FA, was associated with a higher probability of live birth following ART. On the other hand, according to the study by Stanhiser et al., no association was observed between concentration of ɷ-3 FAs and the probability of becoming pregnant naturally. Additionally, the consumption of seafood increases sexual intercourse frequency and provides greater fecundity.

Conversely, MUFAs can bind with the PPAR-γ receptor, thus decreasing inflammation and positively affecting fertility. In fact, studies have presented a positive correlation between the consumption and concentration in plasma of MUFAs, fertility, and the time to achieve pregnancy.

Studies investigating the influence of dairy-derived fats on fertility are interesting, although the results are often contradictory. On the one hand, according to the study by Chavarro et al., the consumption of low-fat dairy—including low-fat milk, yogurt, and cottage cheese—increased the risk of infertility due to anovulation, whereas high-fat dairy increased fertility. This may possibly be associated with a higher content of estrogen and fat-soluble vitamins in high-fat dairy. Moreover, it could also be assumed that the beneficial effect of dairy-derived fat may be associated with the presence of the trans-palmitoleic acid, which seems to improve insulin sensitivity. On the other hand, Wise et al. did not confirm that the consumption of high-fat dairy is correlated with increased fecundity, and they did confirm that consuming lactose and low-fat dairy did not negatively affect fertility.

It is vital to note that the consumption of >3 portions of dairy/d decreases the risk of endometriosis diagnosis by 18%, when compared with the consumption of 2 servings. Additionally, women consuming >4 portions of dairy daily during adolescence presented a 32% lower risk of endometriosis during adulthood than women consuming ≤1 portion. Moreover, the total dairy intake was positively associated with live birth among women aged ≥35 y.

Taking the abovementioned facts into consideration, a high consumption of MUFAs and PUFAs (including a high consumption of ɷ-3 from oily fish or from supplementation) with a low consumption of TFAs and SFAs should be recommended to childbearing-age women trying to become pregnant. Moreover, the evidence for a positive influence of reduced-fat dairy and an increased consumption of high-fat dairy is scarce; thus, it should not be recommended. However, more studies are necessary.

The next element of a fertility diet is protein. Chavarro et al. suggested that animal protein consumption has been associated with a higher risk of infertility due to a lack of ovulation. In turn, the intake of plant protein increases fertility among women >32 y. The difference may stem from the disparate impact of plant and animal protein on insulin and IGF-I secretion. Insulin response is lower after plant protein consumption than following animal protein.

According to Mumford et al., protein intake—in particular animal protein—correlated negatively with testosterone concentrations among healthy women. It seems that androgens, i.e., testosterone, play an important role in regulation of the ovarian function and female fertility. However, excessive androgen signaling seems to be a major factor in androgen-related reproductive disorders, since it disturbs the pathways regulating ovarian follicular dynamics. However, protein intake was not associated with estradiol, progesterone, LH, and FSH concentrations. Additionally, the study showed a lack of association between the total, plant, and animal (without protein from dairy products) protein intake and the amount of antral follicles among women experiencing infertility. On the other hand, a high protein intake from dairy products was connected with a decreased number of antral follicles, which is a biomarker predicting ovarian primordial follicle numbers.

Furthermore, increasing protein intake may improve carbohydrate-insulin balance, which seems to be important in treating infertility due to a lack of ovulation. It is vital to notice that protein presents the highest satiety properties, affects diet-induced thermogenesis, and protects muscle mass.

Future studies on protein's role in the diet of women attempting pregnancy are necessary. In fact, protein should be included in the diet in the amount recommended for the rest of the population, based on such elements as the level of physical activity. Additionally, the diet ought to contain especially plant protein sources.

Folic acid and vitamins B-12 and B-6 

It is possible that folic acid, vitamin B-12, and vitamin B-6 affect fertility. Studies indicate that the supplementation of folic acid (particularly in a dose higher than the recommended one for the prevention of congenital defects and combined with vitamin B-12) in the period prior to pregnancy may increase the chances of becoming pregnant and ART success. However, there is no randomized controlled trial on the impact of a high dose of folic acid associated with a positive response in observational studies.

In fact, fortification of cereals with folic acid increased the number of twin births in the United States. However, this possibly results from an increasing number of women using the ovulation-inducing drugs and not the increased folic acid intake. It is vital to note that folic acid supplementation has been negatively associated with a shorter length of the menstrual cycle. Murto et al. showed that women with unexplained infertility supplemented more folic acid than fertile women. Additionally, women experiencing infertility had higher concentrations of folic acid and lower concentrations of homocysteine when compared with the control group. On the other hand, the intake of synthetic folic acid was associated with an increase in progesterone and a decreased risk of sporadic anovulation.

Additionally, women with methylenetetrahydrofolate reductase (MTHFR) mutation achieved a lower percentage of in vitro fertilizations than subjects without a mutation. On the other hand, the prevalence of implantation and clinical pregnancy was similar in both groups. Moreover, the concentration of vitamin B-12 and folic acid was not associated with in vitro fertilization probability.

The impact of folic acid, vitamin B-12, and vitamin B-6 on fertility is possibly associated with homocysteine metabolism. A lack of vitamin B-12 disturbs the remethylation process, whereas vitamin B-6 deficiency directly leads to an accumulation of homocysteine due to the induction of an enzyme called cystathione b-synthase. Consequently, the transsulfuration process, through which histamine is converted to cysteine, decelerates. Clinical studies show that hyperhomocysteinemia combined with a low concentration of folic acid constitutes a risk factor for recurrent miscarriage. Additionally, a higher homocysteine concentration has been associated with a faulty vascularity of chorion among women with a recurrent early pregnancy loss. In fact, it is homocysteine that induces trophoblast apoptosis and decreases chorionic gonadotropin, whereas a high concentration of homocysteine causes endothelial inflammation through increased expression of proinflammatory cytokines. Moreover, an increased homocysteine concentration in the ovarian follicle liquid may affect the interaction between the ovarian follicle and the spermatozoon, decreasing the chances of fertilization. Additionally, hyperhomocysteinemia increases oxidative stress, which affects women's fertility.

A cohort study including 259 women who were regularly menstruating and not using hormonal contraceptives and diet supplements showed a connection between a higher homocysteine concentration and an increased risk of a lack of ovulation by 33%. Furthermore, a higher folic acid to homocysteine ratio decreased the risk of anovulation by 10%. In fact, mild homocysteinemia is often observed in mothers of children with neural tube defects. It is vital to note that women experiencing PCOS present homocysteine metabolism disorders and a higher concentration of homocysteine in comparison to healthy women. The supplementation of folic acid is recommended for women with PCOS.

Future studies are necessary to confirm whether lowering homocysteine concentrations through diet or supplementation with folic acid and vitamins B-6 and B-12 may improve ovarian function in women attempting pregnancy.

According to the recommendations, women should supplement with folic acid in the period prior to pregnancy, since supplementation is safe and does not cause side effects. Nevertheless, there is a further need for randomized trials confirming the impact of folic acid supplementation on fertility, as well as in doses higher than recommended for preventing neural tube defects.

Vitamin D likely participates in the modulation of female reproductive functions. Studies have demonstrated that vitamin D receptors are expressed in numerous tissues of the reproductive organs, such as ovaries, endometrium, placenta, pituitary gland, and hypothalamus. Additionally, vitamin D affects various endocrine processes and the steroidogenesis of sex hormones. A study indicated that serum concentration of vitamin D may be associated with PCOS and endometriosis and affects the success of ART. On the other hand, there was no association between vitamin D and fertility among healthy subjects. The deficiency of vitamin D affects calcium balance, increases the production and secretion of proinflammatory cytokines, as well as participates in glucose metabolism through stimulating the synthesis and secretion of insulin. Therefore, many studies discuss the impact of vitamin D on inflammatory diseases, including diabetes and cardiovascular disease. Moreover, vitamin D may be an essential component of PCOS development by means of regulating glucose metabolism. In fact, insulin resistance and hyperinsulinemia are associated with enhanced androgen synthesis in the ovaries and a lower concentration of SHGB.

The meta-analysis by He et al. showed a lack of significant differences in vitamin D concentration between women with PCOS and healthy individuals. Nevertheless, the authors emphasized a significantly varied prevalence of vitamin D deficiency among women with PCOS that was associated with comorbidities. In fact, women with PCOS with vitamin D deficiency more frequently presented endocrine and metabolic disorders than women with the normal vitamin D concentrations. It is vital to note that vitamin D has anti-inflammatory and immunomodulating properties, and its deficiency may be associated with endometriosis, which is one of the causes of infertility. In vitro animal studies showed that vitamin D has beneficial effects on endometrial tissues, although clinical studies on the role of vitamin D in the diagnosis and treatment of endometriosis provide inconclusive evidence.

Furthermore, in a meta-analysis, Chu et al. suggest that there is an association between vitamin D status and ART results. Additionally, the authors highlighted that vitamin D deficiency may be an essential factor in infertility treatment using ART. On the other hand, Abadia et al. reported that vitamin D may be linked to a higher rate of fertilization in women undergoing ART. Nevertheless, this was not associated with a higher probability of live birth, or pregnancy.

Future studies are necessary to assess the association between vitamin D and PCOS, endometriosis, and with women's fertility. It is vital to note that a deficiency of vitamin D is common. Individuals presenting too-low concentrations of this vitamin should supplement vitamin D in doses of ≥1500–2000 IU/d.

The proper concentration of minerals is essential for many physiological processes, including maintaining the normal quality of oocytes and embryo fertilization, maturation, and implantation. A deficiency of minerals may disturb fertility; therefore, women should pay attention to the proper intake of minerals and supplement the elements that could be deficient. One study showed that many women fail to meet nutrient needs—particularly in terms of folic acid, calcium, iodine, iron, selenium, vitamin D, and vitamin B-12—and thus have lower blood concentrations. Calcium, iron, zinc, magnesium, iodine, and selenium are especially essential with regard to fertility.

Calcium affects blood vessels, muscle contractions, nerve conduction, and hormone secretion. Additionally, the fetus uses the mother's skeletal calcium for bone growth. Therefore, the recommended dose of calcium constitutes a crucial element in the diet of women of childbearing age. Additionally, calcium deficiency may decrease vitamin D concentrations and increase the risk of hypertension, and pre-eclampsia. However, no studies refer to the validity of the supplementation of or fortification with calcium in the period before pregnancy to prevent pregnancy complications.

Few studies have reported on the association between serum iron concentration and fertility. However, both excess and deficiency of iron may negatively affect fertility. According to Hahn et al., total or heme iron intake was poorly associated with fecundity, particularly among women with a potential risk of iron deficiency, e.g., women with frequent and heavy periods. On the other hand, a prospective study showed that the supplementation of total and nonheme iron may decrease the risk of infertility due to disorders of ovulation.

Another key element is iodine, affecting thyroid gland function, which is essential for proper fertility. In a study conducted in 501 women experiencing moderate or severe iodine deficiency, pregnancy was delayed, and the chances of becoming pregnant in each cycle decreased by 46% when compared with women who were not iodine deficient. Among women with mild iodine deficiency, this association was minimal. It is vital to note that mild and moderate iodine deficiency is common among women of reproductive age around the world.

Grieger et al. reported that low serum concentrations of zinc and selenium were associated with a 1-mo longer period before achieving pregnancy. Additionally, a deficiency of selenium and copper, but not zinc, was linked to a higher risk of infertility. On the basis of limited studies, the impact of zinc and copper concentration on women's fertility remains unclear, and future research is required.

Selenium also affects thyroid gland function. Additionally, it is an antioxidant participating in the reduction of oxidative stress. In fact, selenium possibly influences the growth and maturation of oocytes. Therefore, an adequate supply of selenium is necessary.

Magnesium takes part in glucose metabolism; hence, it may be vital for women with PCOS and metabolic disorders. The proper serum concentration of magnesium is probably associated with increased insulin sensitivity of tissues.

A balanced and varied diet allows for covering the requirements of daily nutrients. However, supplementation is necessary in the case of mineral deficiency, especially with regard to iodine.

The impact of phytoestrogens on fertility has been a highly controversial topic for years. Phytoestrogens are compounds of plant origin, including isoflavones found in soy products; lignans found in nuts, seeds, and cruciferous vegetables; as well as coumestans found in sprouts, peas, and beans.

On one hand, numerous scientific studies indicate the preventive effect of phytoestrogen consumption on the development of breast and endometrial cancer, fibroids, osteoporosis, cardiovascular diseases, inflammation, metabolic syndrome, and obesity. In fact, soy isoflavone supplementation was associated with an increase in the number of live births following clomiphene therapy, increased endometrial thickness, pregnancy rates following insemination, and in vitro fertilization. Furthermore, soy consumption was associated with an increased chance of live birth using ART.

On the other hand, certain studies point to endocrine system disorders as negative effects of phytoestrogen consumption. In the Adventist Health Study, women who consumed a greater amount of isoflavones were at an increased risk of never becoming pregnant and being childless. In contrast, a cohort study by Mumford et al. found no association between soy intake and fertility.

In an analysis of 2 cohorts comprising women planning a pregnancy in North America and Denmark, which included 4880 and 2898 women, respectively, no strong association was observed between dietary phytoestrogen intake and the chances of becoming pregnant. At the same time, it is worth considering that, in Western countries, the average intake of phytoestrogen is 2 mg, and in European countries, the intake is even lower than 1 mg compared with the ∼50 mg consumed in Asian countries.

Undoubtedly, phytoestrogens are still not fully understood; therefore, further research in this area is desirable

Among women struggling with infertility, a discussion of the negative influence of gluten on fertility is relatively common—for instance, the study by Harper and Bold asked subjects about their motivations for eliminating gluten from their diet. However, according to the recommendations, the exclusion of gluten from the diet is not recommended for the general population, and there is no evidence that it is beneficial in non-celiac individuals.

Castaño et al. conducted a meta-analysis that included a total of 23 research studies, and aimed to assess the prevalence of celiac disease seroprevalence in women with fertility disorders. The study group consisted of women with overall infertility, women with idiopathic infertility, and women with recurrent spontaneous abortions. The studies included in the meta-analysis did not comprise women with a diagnosed celiac disease or allergy to wheat proteins. The meta-analysis demonstrated that celiac disease seroprevalence among women with infertility amounted to ∼1.3–1.6%, which allows estimating that women experiencing such disorders are 3 times more likely to develop celiac disease. However, due to the small number of respondents, it is impossible to precisely calculate the total incidence of the association between celiac disease and fertility disorders.

There are no recommendations indicating the benefits of eliminating gluten from the diet of all women experiencing infertility. It should be noted that many research studies indicate a much lower nutritional value of gluten-free diets compared with traditional diets. Nevertheless, such frequent diagnoses of previously undiagnosed celiac disease among women experiencing infertility raises the question of whether it is not reasonable to conduct celiac disease screening tests in women with infertility. However, there can be no doubt that women diagnosed with celiac disease attempting pregnancy should follow a gluten-free diet.

The current knowledge indicates that oxidative stress, i.e., the imbalance between reactive oxygen species (ROS) and antioxidants leading to cell damage, plays an essential role in the development of infertility.

It is assumed that cytochrome P450 is involved in the production of ROS, and oxidative stress subsequently promotes the development of endometriosis, hydrosalpinx, and PCOS. Importantly, oxidative stress has also been shown to be associated with idiopathic infertility, recurrent miscarriage, and pre-eclampsia.

It has been proven that ROS entering the ovum causes damage, which has an important impact on the fertilization process and its further success, as well as the entire process of embryogenesis, which constitutes the reason for a wider use of antioxidants in the treatment of infertility. The possible mechanisms of their action include improving blood circulation in the endometrium, lowering sex hormone concentrations, increasing tissue insulin sensitivity, and affecting ovulation, prostaglandin synthesis, and steroidogenesis.

The most common environmental causes that exacerbate oxidative stress comprise environmental pollutants, smoking, drug use, alcohol abuse, malnutrition, poor diet, and chronic diseases, including obesity and autoimmune diseases.

A Cochrane review indicates that there is evidence based on very-low-quality research suggesting that women experiencing infertility may benefit from antioxidant supplementation. The researchers emphasize that the quality of the available studies is not good enough to establish the possible side effects of the antioxidant supplementation. However, it is worth briefly discussing the individual antioxidants and their potential impact on fertility.

It is worth noting that women with endometriosis have been shown to have a lower supply of vitamins A, C, and E, as well as copper and zinc, than healthy women without fertility disorders. In fact, a 4-mo-long supplementation of vitamins C and E resulted in a reduction in oxidative stress. Additionally, higher levels of oxidative stress markers and lower serum concentrations of vitamins C and E have been observed in women suffering from PCOS.

Vitamin C, vitamin E, and vitamin A are among some of the most potent antioxidants. Vitamin C, which is present in high concentrations in the cytosol of the oocyte, is essential, as it participates in collagen synthesis, which is significant for the growth of the Graaf follicle, ovulation, and the luteal phase. Moreover, vitamin C also helps restore oxidized vitamin E and glutathione. The benefits of vitamin E supplementation include improved epithelial growth in the blood vessels and the endometrium.

Moreover, inositol supplementation may be essential, particularly in PCOS, due to its insulin sensitivity–enhancing and insulin response–modulating effects. Furthermore, inositol derivatives are important secondary messengers of the gonadotropins LH and FSH. Inositol has been shown to regulate the menstrual cycle, improve ovulation, and favorably influence metabolic parameters in women with PCOS, although there is a lack of research evaluating its association with the chances of pregnancy, miscarriage, or the number of deliveries.

Additionally, l-carnitine appears to be an important antioxidant. Research studies indicate that its supplementation relieves disorders of the reproductive system, such as PCOS, endometriosis, or amenorrhea. The alleviating effect of l-carnitine on endometriosis may be due to its impact on the hormonal balance, decreased cytokine release, and apoptosis. By means of its effect on the hypothalamic-pituitary-gonadal axis, l-carnitine regulates the concentrations of gonadotropins and sex hormones and thus may be beneficial for the course of PCOS and the menstrual cycle. l-Carnitine also increases energy production by oocytes through B-oxidation, and is involved in combating oxidative stress . Interestingly, the bioavailability of carnitine from food is much higher than from supplements. Sharkwy et al. conducted research to compare the clinical and metabolic profiles between N-acetylcysteine (NAC) and l-carnitine among women with clomiphene citrate–resistant PCOS. The study demonstrated that both NAC and l-carnitine were effective in improving pregnancy and ovulation rates among women with clomiphene citrate–resistant PCOS. However, although NAC was superior in increasing insulin sensitivity, only l-carnitine improved the lipid profile. In contrast, a study by Behrouzi Lak et al. indicates that, in patients with PCOS without clomiphene citrate resistance, NAC is ineffective in inducing or augmenting ovulation in the PCOS patients who are able to undergo intrauterine insemination and, according to the authors, it cannot be recommended as an adjuvant to clomiphene citrate in such patients.

The composition of the diet also plays an essential role in shaping the intestinal microbiota. Dietary components can either directly impact the gut microbiota by promoting or inhibiting its growth, or indirectly by means of influencing metabolism and the immune system, which can also lead to changes in the gut microbiota composition.

Studies indicate that the consumption of a Western diet has been associated with an increase in Bacteroides phyla and Ruminococcus. On the other hand, a high-fat diet has been positively correlated with the amount of Bacteroides and Actinobacteria simultaneously decreasing Firmicutes and Proteobacteria, which are positively correlated with the consumption of a high-fiber diet. Moreover, diets that are based on animal products have been associated with higher levels of Alistipes, Bilophila, and Bacteroides and with reduced levels of Firmicutes. In contrast, diets high in complex carbohydrates contribute to a beneficial increase in Bifidobacteria, with Prevotella being the most dominant bacterial type among vegetarians. The composition of the intestinal microbiota, largely dependent on diet, plays a vital role in the proper functioning of the immune system. Additionally, intestinal dysbiosis induces local inflammation and an increase in intestinal permeability, which is associated with a decrease in Bifidobacteria. These bacteria, in turn, can reduce LPS and improve the state of the intestinal barrier. All of the above-mentioned facts mean that the Western diet may, in fact, increase the risk of systemic inflammation.

A significant majority of research studies indicate that high caffeine consumption may constitute a potential factor associated with an increased time to achieving pregnancy and an increased risk of pregnancy loss. In addition, a dose-dependent association has been observed between caffeine consumption during pregnancy and stillbirth, childhood acute leukemia, delayed fetal growth, and the negative effects on a child's birth weight, as well as on overweight and obesity in children. According to the European Food Safety Authority, for pregnant women and for women attempting pregnancy, up to 200 mg of caffeine/d is recommended. Similarly, the American College of Obstetricians and Gynecologists indicates that the intake of up to 200 mg of caffeine does not appear to be a main factor leading to miscarriage or preterm delivery. Nevertheless, in the latest review paper including 48 original observational studies and meta-analyses, James emphasized that the assumptions about safe maternal caffeine consumption levels are not supported by the current evidence, and indicated a necessity for a radical revision of the current recommendations. Simultaneously, it is worth noting that the source of caffeine is not only coffee, but also tea, soft drinks, cocoa, or certain drugs.

On the other hand, there is evidence suggesting that alcohol consumption, especially heavy drinking and chronic alcohol consumption, has been connected to reduced fertility and a higher risk of developing menstrual disorders. However, the mechanism in which excessive alcohol consumption negatively affects fertility has not been determined. A suggested hypothesis for the negative influence of alcohol intake on female fertility includes altering endogenous hormone concentrations, a direct impact on the maturation of the ovum, ovulation, early blastocyst development, and implantation. It is also crucial to stress that alcohol consumption during pregnancy can result in adverse effects in offspring development, such as fetal alcohol spectrum disorders.

Diet and nutritional patterns are undoubtedly significant for both male and female fertility; thus, it is worth investigating the components of the diet and their influence on fertility. Further research is needed to develop standardized dietary recommendations for women planning a pregnancy. The current knowledge on the effects of individual nutrients and their sources is summarized in Table 3. Further research is necessary to develop standardized dietary recommendations, which should be given to women planning a pregnancy, and individualized in case of problems with achieving pregnancy. It is important to emphasize the valid role of a clinical dietitian, who should actively participate in the care of women planning a pregnancy and, above all, be a member of a multidisciplinary team in infertility treatment centers.

TABLE 3

The effects of the selected dietary components on female fertility¹

¹ART, assisted reproductive technology; NAC, N-acetylcysteine; PCOS, polycystic ovary syndrome; TFA, trans-fatty acid.

Conclusions

Numerous questions remain unanswered, although there is no doubt that diet has an impact on female fertility. On the basis of the current knowledge, it can be confirmed that the consumption of TFAs, refined carbohydrates, and added sugars negatively affects female fertility. In contrast, a diet based on the recommendations of the MeD—rich in dietary fiber, ɷ-3 FAs, vegetable protein, vitamins, and minerals—has a positive effect on female fertility.

There are no clear guidelines on supplementation to enhance fertility in women. A properly balanced diet should provide all minerals and vitamins, except for vitamin D and folic acid, which should be supplemented. It may also be challenging to provide adequate amounts of iodine with the diet, especially in low-sodium diets and in elimination diets. Additionally, women in the period prior to pregnancy are also recommended to consume folic acid. Particularly in women considered as a risk group, serum concentrations of micronutrients and vitamins should be monitored, and in the case of deficiencies, supplementation should be introduced.

Abstract

Despite growing evidence of the impact of diet on human fertility, few studies have examined the public health implications of this association in the United States (U.S.). This narrative review summarizes current scientific evidence on associations between dietary intake and fertility, discusses challenges in the public health landscape surrounding infertility, and proposes evidence-based recommendations to address these issues. Diets high in unsaturated fats, whole grains, vegetables, and fish have been associated with improved fertility in both women and men. While current evidence on the role of dairy, alcohol, and caffeine is inconsistent, saturated fats, and sugar have been associated with poorer fertility outcomes in women and men. Furthermore, women and men with obesity [body mass index (BMI) ≥ 30 kg/m²] have a higher risk of infertility. This risk is extended to women who are underweight (BMI 20 kg/m²). Diet and BMI influence outcomes during clinical treatment for infertility. Further, women in the U.S. who belong to an underrepresented minority group, have low income, or have low educational attainment, have significantly higher rates of infertility outcomes as compared to women who are non-Hispanic white, have high income, or have high educational attainment. Given this, it may be prudent to integrate nutrition counseling into both clinical guidelines for infertility as well as national dietary guidelines for individuals of reproductive age. Further studies on diet and reproductive health may enhance our ability to improve existing fertility programs across the U.S. and to deliver tailored care to women and men within at-risk groups.

The experience of infertility can exact a significant physical, psychosocial, and economic toll on couples. An estimated 15% of couples in the United States (U.S.) are affected by infertility, defined as the failure to achieve pregnancy after 12 months of unprotected sexual intercourse. Although infertility is often associated with women, male physiological factors have been shown to be responsible for ~25% of cases, underscoring the need to consider both partners. The incidence of infertility has remained high despite increased use of assisted reproductive technologies (ART) in recent years. As such, research has aimed to identify modifiable risk factors for infertility; to date, nutritional factors have been the subject of much of this investigation. Evidence suggests that nutrition can play an important role in altering fertility-related outcomes in both men and women. The purpose of this article is to summarize the literature on the nutritional factors related to infertility and to consider the public health implications of this body of research within the landscape of the U.S (Figure ​(Figure11).

Figure 1

The interconnection between dietary, lifestyle, sociodemographic, and psychosocial factors on fertility outcomes. This conceptual framework shows the interconnections between dietary, lifestyle, sociodemographic, and psychosocial factors on fertility outcomes. Dietary factors, both protective and harmful, have bidirectional relationships with sociodemographic, psychosocial, and lifestyle risk factors. Dietary factors independently, as well as together with these correlated factors, impact multiple fertility outcomes.

There is strong evidence that healthy preconception dietary patterns among both men and women of reproductive age have a beneficial effect on fertility. A dietary pattern consistent with the recommendations put forth by the U.S. Dietary Guidelines for Americans, which recommends a high consumption of whole grains, monounsaturated or polyunsaturated oils, vegetables, fruits, and fish, has been associated with improved fertility in women and higher semen quality in men. In the Nurses' Health Study (NHS) II, a large prospective cohort, women who had the highest intake of a “fertility diet” comprised of plant protein from vegetable sources, full-fat dairy foods, iron, and monounsaturated fats, during the preconception period, were found to have a 66% (95% CI, 52, 77%) lower risk of infertility related to ovulatory disorders and a 27% (95% CI, 5, 43%) lower risk of infertility due to other causes compared to women with the lowest intake of this diet pattern, controlling for age, body mass index (BMI), alcohol intake, coffee intake, smoking, and oral contraceptive use. Population attributable risk calculations based on this sample suggest that not following the “fertility diet” was the attributable factor in 46% of cases of infertility, which was higher than all other independent risk factors (e.g., BMI, physical activity). In another study of college-educated women in Spain, those in the highest quartile of adherence to a Mediterranean-style diet, which similarly included high intake of vegetables, fish, and polyunsaturated oils, had 44% (95% CI, 35, 95%) lower odds of seeking medical help for difficulty getting pregnant compared to women in the lowest quartile. The Mediterranean diet yielded similar benefits on achieving clinical pregnancy and live birth among non-obese women in Greece, but only for those below the age of 35. Furthermore, data indicate that a healthy diet, consisting of the aforementioned food groups, improves measures of semen quality, including morphology, motility, and concentration.

Data on the associations of specific nutrients and foods with fertility may yield important insight into the possible mechanisms linking diet and reproductive health. In addition to being linked to neural tube defects in infants, low levels of folate are associated with a lower frequency of sporadic anovulation. In a randomized controlled trial of subfertile women who took a multivitamin containing 400 μg of folic acid for 3 months, 26% had a pregnancy compared to 10% of women in the placebo group. However, the dose-response benefit of folate appears to extend beyond the current recommended dose for reproductive-aged women (400 μg). Gaskins et al. found that higher levels of pre-pregnancy folate supplementation were associated with a lower risk of spontaneous abortion, but only when comparing those who consumed greater than 730 μg per day of supplemental folate with those who did not consume any folate from supplements.

Preliminary data suggest that red meat may have an adverse effect on fertility. Results from an infertility cohort study showed that consumption of red meat was negatively associated (OR: 0.81; 95% CI, 0.65, 0.99) with likelihood of blastocyst formation during embryo development. Notably, iron intake may be reduced if red meat intake is restricted; yet it has been shown that consuming iron supplements and non-heme iron from other sources may decrease the risk of ovulatory infertility. Saturated fat content, which can be particularly high in red meat, has independently been linked to lower semen concentration in males. Polyunsaturated fats, conversely, have been shown to yield reproductive benefits in both men and women. A cross-sectional study of men showed that higher intake of omega-3 fatty acids was associated with significantly more favorable sperm morphology. Women who consumed higher levels of omega-6, linoleic acid, and omega-3 had a higher incidence of pregnancy than those with lower intake of these nutrients.

Current research examining the effect of dairy on fertility is limited in scope. One study found few and inconsistent associations between preconception dairy intake and fertility in two cohorts of reproductive-aged women. In the NHS II, however, while no relationship was found between total intake of dairy products and risk of infertility, full-fat dairy products were associated with a lower risk of ovulatory infertility while low-fat dairy products (including skim, 1%, and 2% milk, yogurt, or cottage cheese) were associated with a higher risk.

Studies have similarly yielded inconclusive evidence on the effect of alcohol and caffeine intake on fertility. Chavarro et al. found that neither alcohol nor caffeine intake appeared to impair ovulation to the point of decreasing fertility in NHS. While men with caffeine intake greater than 272 mg/day and alcohol intake over 22 g/day have been linked to lower adjusted live birth rates after use of ART, intake of these substances has not been shown to affect semen quality. In another prospective cohort study of 3,628 women planning to become pregnant, women who reported consuming 3 or more servings of soda per day had a 52% lower (95% CI, 0.21, 1.13) rate of pregnancy compared to women who did not report any soda consumption, while there was no association found between coffee consumption and fertility. These results may be indicative of the adverse effects of sugar intake on fertility among women, although further studies on this topic are needed. Existing data suggest that high consumption of sugar is associated with lower semen quality and increased infertility among men.

Current research indicates a roughly “J”-shaped relationship between BMI and fertility, such that the risk of infertility is highest among those at the lowest and highest ends of the BMI distribution. In the NHS II, compared to women classified as having recommended weight (BMI 20–25 kg/m²), a higher risk of ovulatory disorder infertility was observed for women classified as underweight (BMI 20 kg/m²; RR: 1.38; 95% CI, 1.03, 1.85) and for women with obesity (BMI ≥ 30 kg/m²; RR: 2.35; 95% CI, 1.78, 3.11), after controlling for diet, age, smoking, and oral contraceptive use. Additionally, a review of the literature related to male obesity and fertility concluded that male obesity is associated with increased risk of infertility, potentially through endocrine dysregulation mechanisms. Obesity status has also been linked to ART treatment success. Among a nationally representative sample of U.S. women using ART, a BMI between 30 and 35 kg/m² was associated with significantly greater odds (OR: 1.14; 95% CI, 1.09, 1.19) of failing to achieve a clinical intrauterine gestation compared to women in a reference group with BMI 18.5-25 kg/m².

There is limited data on the extent to which BMI modifies the relationship between dietary (and other) factors and infertility. Chavarro et al. found that the relationship between an ideal dietary pattern and risk of infertility was not modified by BMI; although the absolute risk of ovulatory disorder infertility was higher in those with a BMI over 25 kg/m² compared to those with a recommended BMI; the extent to which dietary improvements attenuated that risk was similar in both groups. Furthermore, physical activity levels also reduced the risk of ovulatory disorder infertility similarly across BMI categories.

A recent systematic review explored the impact of weight loss interventions among participants with overweight or obesity status on fertility-related outcomes. Among women, a pooled analysis of randomized studies found that participants randomized to active diet and exercise interventions were more likely (RR: 1.59; 95% CI, 1.01, 2.50) to become pregnant compared to control participants. While the literature was more sparse for men, one diet and exercise intervention in a cohort of subfertile men yielded significant improvements in the degree of sperm DNA fragmentation.

Given the rigorous evidence presented above that suggests that various aspects of nutrition contribute to a reduced risk of fertility problems in the general reproductive-aged population and may also be an effective treatment for men and women already experiencing infertility, nutrition, and/or obesity counseling is likely to be central in fertility treatment. Obesity assessment is customary during the treatment process; 43% of U.S.-based infertility clinics included in a survey had a BMI cutoff for performing ART procedures, while 83% of the directors of clinics surveyed believed that a standard cutoff should exist. When asked about the weight loss method that they recommended to patients with an elevated BMI, 95% of respondents reported that they counseled their patients on proper diet and exercise, and 90% reported referring their patients to a nutritionist. This course of action is promising given the effectiveness of weight loss interventions on fertility outcomes. However, as noted above, evidence suggests that following a healthy diet provides a similar magnitude of benefit on fertility regardless of BMI status. Thus, it may be prudent to consider expanding weight-loss or nutritional advice to all individuals accessing infertility treatment, while continuing to prioritize those who are below or above certain BMI cutoffs. One way to support this would be to include nutritional counseling in national clinical guidelines for fertility. For example, the National Institute for Health and Care Excellence in the United Kingdom included in their 2013 fertility treatment guidelines that providers should inform patients experiencing difficulty becoming pregnant that either partner having a BMI > 30 kg/m² may have a reduced chance of conception, and that losing weight might improve the chances of becoming pregnant. Nonetheless, fertility-promoting diets are not specifically mentioned in these clinical practice guidelines.

Women who experience issues with fertility are at an increased risk of depression relative to women not experiencing such problems. Moreover, women with pre-existing depression may be more likely to experience infertility due to physiological changes in hormone production and ovulation. A recent meta-analysis reported higher achievement of pregnancies or live births among women with lower pre-pregnancy depression or anxiety. Moreover, among men, exposure to occupational stressors was negatively associated with semen quality. As such, it is critical to understand how to manage depression and other psychosocial factors in women and men who are contemplating or having difficulty becoming pregnant. Beyond the effect of a healthy diet on fertility-related outcomes, certain dietary patterns have been shown to protect against depression. For example, participants randomized to a Mediterranean diet had a lower risk of depression compared to control participants who were assigned to a low-fat diet, especially among those with preexisting type 2 diabetes. Furthermore, the relationship between low folate status, a risk factor for subfertility, and depression has been well-characterized in the literature. Therefore, promoting healthy dietary patterns and higher folate intake among individuals experiencing infertility may improve their chances of achieving a pregnancy and concomitantly temper the psychological burden associated with their experience. However, current guidelines for psychosocial counseling in infertility treatment do not include nutritional advice as a factor that clinicians should consider.

While several foods and nutrients that may protect against infertility are consistent with current federal nutrition guidelines—such as the USDA Dietary Guidelines for Americans—the connection between diet and fertility is not mentioned. This omission may limit recommendations of foods and nutrients that have strong evidence for improved fertility at the population level. For example, women of reproductive age are recommended to consume 400 μg of folic acid per day, but evidence suggests that higher consumption pre-pregnancy may lower the risk of some infertility outcomes. Furthermore, while fish high in omega-3 fatty acid content are generally recommended as part of a healthy diet, there is potential for environmental contamination from mercury and other toxins in some specific type of fish. Although studies have reported mostly null associations between mercury intake and fertility or reproductive outcomes, specific recommendations for fish intake are made for pregnant women or women of childbearing age. Nonetheless, omega-3 fatty acid intake should still be recommended to these groups as part of a healthy fertility diet. Recognizing the types and quantities of foods that contribute to reproductive health may improve national nutrition guidelines.

In the U.S., women with lower income or lower educational attainment experience a higher prevalence of infertility outcomes compared to those with higher income or educational attainment, while Hispanic and non-Hispanic Black women have a higher prevalence of infertility compared to non-Hispanic white women. The disparity in fertility rates may partially be explained by nutritional intake, as recent data from a large cohort (n = 7,511) of nulliparous women showed that in the months prior to conception, women with lower educational attainment or who were Hispanic or non-Hispanic Black, had a poorer general diet than women with higher educational attainment or who were non-Hispanic White. Disparities have also been reported in receipt of preventive services for optimal diet and health for conception among U.S. women and men of reproductive age. These results reflect the current state in the general U.S. population, as groups who are racial/ethnic minorities or have lower education tend to have poorer diet quality as well as a higher prevalence of obesity, which is another risk factor for infertility.

This mini-review summarizes existing evidence on the relationship between fertility and nutrition. While there is a well-characterized association between high intake of folic acid, polyunsaturated fats, and plant-based foods on fertility outcomes, further research is required to more clearly understand the roles of other foods. Future research should also consider the need for randomized controlled trials and studies examining the combined effects of diets of both male and female partners on fertility. Despite recent progress in the amount of literature on the relationship between fertility and diet, this is the first article, to our knowledge, to specifically focus on the public health implications of this connection; a few articles have briefly and partly discussed the topic. Thus, there is a need for more standardized integration of nutrition counseling into treatment delivery for infertility. Incorporating specific guidelines for individuals of reproductive age when developing federal nutritional guidelines may also impact the reach of this information. Furthermore, there is an urgent need to develop targeted messaging and interventions among individuals with extreme BMI categories, racial/ethnic minorities, and low-income and low-education groups in order to improve existing disparities in both fertility and overall health outcomes in the U.S.

Given the positive effect of a healthy diet on fertility outcomes, and the implications for public health and clinical practice noted above, several recommendations can be noted. First, clinicians should provide counseling to improve dietary behaviors among patients accessing ART services, regardless of BMI while prioritizing those with unfavorable BMI. Specifically, a diet consistent with the U.S. Dietary Guidelines for Americans and adequate levels of folic acid intake for women could be recommended. Moreover, patients with a BMI consistent with underweight, overweight, or obesity status should be referred to nutritional and weight-loss counseling to help improve the likelihood of positive fertility outcomes. In order for health care providers to have the best and most current information on the effects of specific dietary components on fertility, there should be clear and effective communication between researchers and clinicians.

A second recommendation is to improve the delivery of nutritional programs and interventions aimed at the general reproductive-aged population, as well as targeted at-risk groups. For example, considering accessibility of an intervention has been cited as an important factor contributing to young adults' willingness to participate in a weight loss program. Thus, leveraging the ubiquity of mobile technology, such as text messaging or a Smartphone application, to deliver a healthy eating or weight loss intervention has been shown to be an effective strategy to engage this sector of the population. Given the sociodemographic and racial/ethnic disparities in infertility, efforts to improve the diets of reproductive-aged adults should target low socioeconomic or education groups and racial/ethnic minority populations. Interventions should consider the unique barriers these groups face related to optimal nutrition, including structural barriers such as access to healthy foods in terms of geographic accessibility as well as price. Approaches that considers the structural barriers to a healthy diet among this target population may involve limiting the extent to which the U.S. government-assisted food benefit program Supplemental Nutrition Assistance Program can be used to purchase foods that contribute to infertility, such as sugary beverages, or incentivizing the purchase of foods consistent with a healthy diet pattern for reproductive-aged adults through a program similar to the Healthy Incentive Program.

In order to lend further support to fertility-promoting diets for the population, a third recommendation is to include evidence-based messaging in population-wide nutritional guidelines such as the U.S. Dietary Guidelines for Americans. The public health implications of nutrition and fertility in the U.S. are multifaceted. Future research and collaboration across stakeholders in research institutions, clinical practice, and the community will help drive and implement more evidence-based recommendations and interventions.

Research consistently shows that lifestyle factors—what you eat, how well you sleep, where you live, and other behaviors—have profound effects on health and disease. Fertility is no exception.

A number of lifestyle factors affect fertility in women, in men, or in both. These include but are not limited to nutrition, weight, and exercise; physical and psychological stress; environmental and occupational exposures; substance and drug use and abuse; and medications.

For example, research shows that:

• Obesity is linked to lower sperm count and quality in men.
• Among obese women who have polycystic ovary syndrome (PCOS), losing 5% of body weight greatly improves the likelihood of ovulation and pregnancy.
• Being underweight is linked to ovarian dysfunction and infertility in women.
• Strenuous physical labor and taking multiple medications are known to reduce sperm count in males.
• Excessive exercise is known to affect ovulation and fertility in women.
• Research shows that using body-building medications or androgens can affect sperm formation.
• Substance use, including smoking tobacco, using other tobacco products, marijuana use, heavy drinking, and using illegal drugs such as heroin and cocaine reduce fertility in both men and women.
• Having high blood pressure changes the shape of sperm, thereby reducing fertility.
• The type of underwear a man chooses is not related to his infertility.
• Radiation therapy and chemotherapy can cause infertility in females and males. Those who have to undergo these types of treatments may want to consider fertility preservation.

NICHD research also shows that exposure to persistent organic pollutants and endocrine-disrupting chemicals (EDCs) in the environment can also affect male and female fertility.

Persistent organic are currently used or were formerly used in industrial processes and remain in the environment much longer than other chemicals. Animal studies suggest that exposure to certain persistent organic pollutants affects fertility. NICHD's Longitudinal Investigation of Fertility and the Environment (LIFE) Study is examining whether exposure to persistent organic pollutants affects the length of time it takes for couples to become pregnant, a measure of fecundity. It is the only study to measure chemicals in both partners and to follow couples trying to become pregnant for 1 year.

So far, the study has found that certain kinds of organochlorine pesticides and many polychlorinated biphenyls (PCBs) were linked to increased time-to-pregnancy or decreased couple fecundity. The study found that many chemicals only affected time-to-pregnancy when found in high levels in the male partner, whereas other chemicals only affected fecundity when detected in the female partner. Other studies have linked exposure to TCCD dioxin and select polybrominated diethers and perfluorochemicals to reduced fecundity.

EDCs alter the function of the hormonal system, a key component in fertility. The LIFE study found that the EDC methyl paraben affects fertility in women, while phthalates and the UV filter benzophenone-2 affect fertility in men.

What is infertility?

In general, infertility is defined as not being able to get pregnant (conceive) after one year (or longer) of unprotected sex. Because fertility in women is known to decline steadily with age, some providers evaluate and treat women aged 35 years or older after 6 months of unprotected sex. Women with infertility should consider making an appointment with a reproductive endocrinologist—a doctor who specializes in managing infertility. Reproductive endocrinologists may also be able to help women with recurrent pregnancy loss, defined as having two or more spontaneous miscarriages.

Pregnancy is the result of a process that has many steps.

To get pregnant

• A woman’s body must release an egg from one of her ovaries (ovulation).
• A man’s sperm must join with the egg along the way (fertilize).
• The fertilized egg must go through a fallopian tube toward the uterus (womb).
• The fertilized egg must attach to the inside of the uterus (implantation).

Infertility may result from a problem with any or several of these steps.

Impaired fecundity is a condition related to infertility and refers to women who have difficulty getting pregnant or carrying a pregnancy to term.

Yes. In the United States, among married women aged 15 to 49 years with no prior births, about 1 in 5 (19%) are unable to get pregnant after one year of trying (infertility). Also, about 1 in 4 (26%) women in this group have difficulty getting pregnant or carrying a pregnancy to term (impaired fecundity).

Infertility and impaired fecundity are less common among women with one or more prior births. In this group, about 6% of married women aged 15 to 49 years are unable to get pregnant after one year of trying and 14% have difficulty getting pregnant or carrying a pregnancy to term.

No, infertility is not always a woman’s problem. Both men and women can contribute to infertility.

Infertility in men can be caused by different factors and is typically evaluated by a semen analysis. When a semen analysis is performed, the number of sperm (concentration), motility (movement), and morphology (shape) are assessed by a specialist. A slightly abnormal semen analysis does not mean that a man is necessarily infertile. Instead, a semen analysis helps determine if and how male factors are contributing to infertility.

Disruption of testicular or ejaculatory function

• Varicocele, a condition in which the veins within a man’s testicle are enlarged. Although there are often no symptoms, varicoceles may affect the number or shape of the sperm.
• Trauma to the testes may affect sperm production and result in lower number of sperm.
• Heavy alcohol use, smoking, anabolic steroid use, and illicit drug use.
• Cancer treatment involving certain types of chemotherapy, radiation, or surgery to remove one or both testicles.
• Medical conditions such as diabetes, cystic fibrosis, certain types of autoimmune disorders, and certain types of infections may cause testicular failure.

Hormonal disorders

• Improper function of the hypothalamus or pituitary glands. The hypothalamus and pituitary glands in the brain produce hormones that maintain normal testicular function. Production of too much prolactin, a hormone made by the pituitary gland (often due to the presence of a benign pituitary gland tumor), or other conditions that damage or impair the function of the hypothalamus or the pituitary gland may result in low or no sperm production.
• These conditions may include benign and malignant (cancerous) pituitary tumors, congenital adrenal hyperplasia, exposure to too much estrogen, exposure to too much testosterone, Cushing’s syndrome, and chronic use of medications called glucocorticoids.

Genetic disorders

• Genetic conditions such as a Klinefelter’s syndrome, Y-chromosome microdeletion, myotonic dystrophy, and other, less common genetic disorders may cause no sperm or low numbers of sperm to be produced.

• Age. Although advanced age plays a much more important role in predicting female infertility, couples in which the male partner is 40 years old or older are more likely to report difficulty conceiving.
• Being overweight or obese.
• Smoking.
• Excessive alcohol and drug use (opioids, marijuana).
• Exposure to testosterone. This may occur when a doctor prescribes testosterone injections, implants, or topical gel for low testosterone, or when a man takes testosterone or similar medications illicitly for the purposes of increasing their muscle mass.
• Exposure to radiation.
• Frequent exposure of the testes to high temperatures, such as that which may occur in men confined to a wheelchair, or through frequent sauna or hot tub use.
• Exposure to certain medications such as flutamide, cyproterone, bicalutamide, spironolactone, ketoconazole, or cimetidine.
• Exposure to environmental toxins including exposure to pesticides, lead, cadmium, or mercury.

Women need functioning ovaries, fallopian, and a uterus to get pregnant. Conditions affecting any one of these organs can contribute to female infertility. Some of these conditions are listed below and can be evaluated using several different tests.

Disruption of ovarian function (presence or absence of ovulation and effects of ovarian “age”)

A woman’s menstrual cycle is, on average, 28 days long. Day 1 is defined as the first day of “full flow.” Regular predictable periods that occur every 21 to 35 days likely reflect ovulation. A woman with irregular periods is likely not ovulating.

Ovulation can be predicted by using an ovulation predictor kit and can be confirmed by a blood test to check the woman’s progesterone level on day 21 of her menstrual cycle. Although several tests exist to evaluate a woman’s ovarian function, no single test is a perfect predictor of fertility. The most commonly used markers of ovarian function include follicle-stimulating hormone (FSH) value on day 3 to 5 of the menstrual cycle, anti-müllerian hormone value (AMH), and antral follicle count (AFC) using a transvaginal ultrasound.

Disruption in ovarian function may be caused by several conditions and warrants an evaluation by a doctor.

When a woman doesn’t ovulate during a menstrual cycle, it’s called anovulation. Potential causes of anovulation include the following

• Polycystic ovary syndrome (PCOS). PCOS is a condition that causes women to not ovulate, or to ovulate irregularly. Some women with PCOS have elevated levels of testosterone, which can cause acne and excess hair growth. PCOS is the most common cause of female infertility.
• Diminished ovarian reserve (DOR). Women are born with all of the eggs that they will ever have, and the number of eggs declines naturally over time. DOR is a condition in which there are fewer eggs remaining in the ovaries than expected for a given age. It may occur due to congenital (condition present at birth), medical, surgical, or unexplained causes. Women with DOR may be able to conceive naturally, but will produce fewer eggs in response to fertility treatments.
• Functional hypothalamic amenorrhea (FHA). FHA is a condition caused by excessive exercise, weight loss, stress, or often a combination of these factors. It is sometimes associated with eating disorders such as anorexia.
• Improper function of the hypothalamus and pituitary glands. The hypothalamus and pituitary glands in the brain produce hormones that maintain normal ovarian function. Production of too much of the hormone prolactin by the pituitary gland (often as the result of a benign pituitary gland tumor), or improper function of the hypothalamus or pituitary gland, may cause a woman not to ovulate.
• Premature ovarian insufficiency (POI). POI, sometimes referred to as premature menopause, occurs when a woman’s ovaries fail before she is 40 years of age. Although certain exposures, such as chemotherapy or pelvic radiation therapy, and certain medical conditions may cause POI, the cause is often unexplained. About 5% to 10% of women with POI conceive naturally and have a normal pregnancy.
• Menopause. Menopause is a natural decline in ovarian function that usually occurs around age 50. By definition, a woman in menopause has not had a period for at least one year. Many women experience hot flashes, mood changes, difficulty sleeping, and other symptoms as well.

Fallopian tube obstruction (whether fallopian tubes are open, blocked, or swollen)

Risk factors for blocked fallopian tubes (tubal occlusion) can include a history of pelvic infection, ruptured appendix, gonorrhea, chlamydia, endometriosis, or prior abdominal surgery.

Fallopian tubes may be evaluated by hysterosalpingogram or by chromopertubation.

• Hysterosalpingogram is an X-ray of the uterus and fallopian tubes. A radiologist injects dye into the uterus through the cervix and simultaneously takes X-ray pictures to see if the dye moves freely through fallopian tubes indicating they are open.
• Chromopertubation is similar to a hysterosalpingogram but is done in the operating room at the time of a laparoscopy. Blue-colored dye is passed through the cervix into the uterus and through the fallopian tubes. This test is used to evaluate if the fallopian tubes are open and to assess if they are dilated.

Physical characteristics of the uterus

Depending on a woman’s symptoms, the uterus may be evaluated by transvaginal ultrasound to look for fibroids or other problems, including intrauterine adhesions, endometrial polyps, adenomyosis, and congenital anomalies of the uterus. A sonohystogram or hysteroscopy may also be performed to further evaluate the uterine environment.

Female fertility is known to decline with

• Age. About 1 in 5 (22%) married couples in which the woman is 30-39 have problems conceiving their first child compared to about 1 in 8 (13%) married couples in which the woman is younger than 30. Fertility declines with age primarily because egg quality declines over time. In addition, older women have fewer eggs left and they are more likely to have health conditions that can cause fertility problems. Aging also increases a woman’s chances of miscarriage and of having a child with a genetic abnormality.
• Smoking.
• Excessive alcohol use.
• People with overweight or obesity or underweight.
• Extreme weight gain or loss.
• Excessive physical or emotional stress that results in amenorrhea (absent periods).

A woman’s chances of having a baby decrease rapidly every year after the age of 30. Most experts suggest women younger than age 35 with no apparent health or fertility problems and regular menstrual cycles should try to conceive for at least one year before seeing a doctor. However, for women aged 35 years or older, couples should see a health care provider after 6 months of trying unsuccessfully. Women over 40 years may consider seeking more immediate evaluation and treatment.

Some health problems also increase the risk of infertility. So, couples with the following signs or symptoms should not delay seeing their health care provider when they are trying to become pregnant:

For women:

• Irregular periods or no menstrual periods
• Endometriosis
• A history of pelvic inflammatory disease
• Known or suspected uterine or tubal disease
• A history of more than one miscarriage
• Genetic or acquired conditions that predispose to diminished ovarian reserve (chemotherapy, radiation)

For men:

• A history of testicular trauma
• Prior hernia surgery
• Prior use of chemotherapy
• A history of infertility with another partner
• Sexual dysfunction

It is a good idea for any woman and her partner to talk to a health care provider before trying to get pregnant. They can help you get your body ready for a healthy baby, and can also answer questions on fertility and give tips on conceiving.

Doctors will begin by collecting medical and sexual history from both partners. The initial evaluation usually includes a semen analysis, a tubal evaluation, and ovarian reserve testing.

Infertility can be treated with medicine, surgery, intrauterine insemination, or assisted reproductive technology.

Often, medication and intrauterine insemination are used at the same time. Doctors recommend specific treatments for infertility on the basis of:

• The factors contributing to the infertility.
• The duration of the infertility.
• The age of the female.
• The couple’s treatment preference after counseling about success rates, risks, and benefits of each treatment option.

Male infertility may be treated with medical, surgical, or assisted reproductive therapies depending on the underlying cause. Medical and surgical therapies are usually managed by a urologist who specializes in infertility. A reproductive endocrinologist may offer intrauterine inseminations (IUIs) or in vitro fertilization (IVF) to help overcome male factor infertility.

Some common medicines used to treat infertility in women include:

• Clomiphene citrate (Clomid®*) is a medicine that causes ovulation by acting on the pituitary gland. It is often used in women who have polycystic ovary syndrome (PCOS) or other problems with ovulation. It is also used in women with normal ovulation to increase the number of mature eggs produced. This medicine is taken by mouth.
• Letrozole (Femara®*) is a medication that is frequently used off-label to cause ovulation. It works by temporarily lowering a woman’s progesterone level, which causes the brain to naturally make more follicle-stimulating hormone (FSH). It is often used to induce ovulation in woman with PCOS, and in women with normal ovulation to increase the number of mature eggs produced in the ovaries. It is taken by mouth.
• Human menopausal gonadotropin or hMG (Menopur®*; Repronex®*; Pergonal®*) is an injectable medication often used for women who don’t ovulate because of problems with their pituitary gland—hMG acts directly on the ovaries to stimulate development of mature eggs.
• Follicle-stimulating hormone or FSH (Gonal-F®*; Follistim®*) is an injectable medication that works much like hMG. It stimulates development of mature eggs within the ovaries.
• Gonadotropin-releasing hormone (GnRH) analogs and GnRH antagonists are medications that act on the pituitary gland to prevent a woman from ovulating. They are used during in vitro fertilization cycles, or to help prepare a woman’s uterus for an embryo transfer. These medications are usually injected or given with a nasal spray.
• Metformin (Glucophage®*) is a medicine doctors use for women who have insulin resistance or diabetes and PCOS. This drug helps lower the high levels of male hormones in women with these conditions. This helps the body to ovulate. Sometimes clomiphene citrate or FSH is combined with metformin. This medicine is taken by mouth.
• Bromocriptine (Parlodel®*) and Cabergoline (Dostinex®*) are medications used for women with ovulation problems because of high levels of prolactin. These medications are taken by mouth.

*Note: Use of trade names and commercial sources is for identification only and does not imply endorsement by the US. Department of Health and Human Services.

Many fertility drugs increase a woman’s chance of having twins, triplets, or other multiples. Women who are pregnant with multiple fetuses may have more problems during pregnancy. Multiple fetuses have a higher risk of being born prematurely (too early). Premature babies are at a higher risk of health and developmental problems.

Intrauterine insemination (IUI) is an infertility treatment that is often called artificial insemination. In this procedure, specially prepared sperm are inserted into the woman’s uterus. Sometimes the woman is also treated with medicines that stimulate ovulation before IUI.

IUI is often used to treat:

• Mild male factor infertility.
• Couples with unexplained infertility.

Assisted Reproductive Technology (ART) includes all fertility treatments in which either eggs or embryos are handled outside of the body. In general, ART procedures involve removing mature eggs from a woman’s ovaries using a needle, combining the eggs with sperm in the laboratory, and returning the embryos to the woman’s body or donating them to another woman. The main type of ART is in vitro fertilization (IVF).

Success rates vary and depend on many factors, including the clinic performing the procedure, the infertility diagnosis, and the age of the woman undergoing the procedure. This last factor—the woman’s age—is especially important.

CDC publishes ART success rates for all fertility clinics in the United States. In addition, CDC created an IVF Success Estimator – a tool to estimate the chance of having a live birth using IVF based on the experiences of women and couples with similar characteristics.

ART can be expensive and time-consuming, but it has allowed many couples to have children that otherwise would not have been conceived. The most common complication of ART is a multiple pregnancy. This is a problem that can be prevented or minimized by limiting the number of embryos that are transferred back to the uterus. For example, transfer of a single embryo, rather than multiple embryos, greatly reduces the chances of a multiple pregnancy and its risks such as preterm birth.

• In vitro fertilization (IVF), meaning fertilization outside of the body, is the most common form of ART. Eggs and sperm are combined in a laboratory to create embryos. After about three to five days, the embryo (or embryos) is transferred into the woman’s uterus. Embryos can also be frozen for a future transfer. When a frozen embryo is thawed and transferred into a woman’s uterus it is called a frozen embryo transfer (FET).
• Intracytoplasmic sperm injection (ICSI) is a type of IVF that is often used for couples with male factor infertility. With ICSI, a single sperm is injected into a mature egg. The alternative to ICSI is “conventional” fertilization where the egg and many sperm are placed in a petri dish together and the sperm fertilizes an egg on its own.
• Zygote intrafallopian transfer (ZIFT) or tubal embryo transfer and gamete intrafallopian transfer (GIFT) are other ART methods that are rarely used in the United States today. With ZIFT, fertilization occurs in the laboratory similar to IVF. Then the very young embryo is transferred to the fallopian tube instead of the uterus. GIFT involves transferring eggs and sperm into the woman’s fallopian tube and fertilization occurs in the woman’s body.

ART procedures sometimes involve the use of donor eggs (eggs from another woman), donor sperm, or donated embryos. Donor eggs are sometimes used for women who cannot produce eggs. Also, donor eggs or donor sperm are sometimes used when the woman or man has a genetic disease that can be passed on to the baby. An infertile couple may also use donated embryos that were created by other couples in infertility treatment and were not used. When donated embryos are used the child will not be genetically related to either parent. Donor eggs, sperm, or donated embryos may also be used by same-sex couples.

Women with ovaries but no uterus may be able to use a gestational carrier. This may also be an option for women who shouldn’t become pregnant because of a serious health problem. In this case, a woman uses her own egg and it is fertilized by her partner’s sperm. Then, the embryo is placed inside the carrier’s uterus.

Preimplantation genetic testing is a procedure used to identify genetic disorders or chromosomal abnormalities in embryos created during an IVF cycle. One or more cells are biopsied from each embryo and sent for testing. These procedures used to be referred to as preimplantation genetic screening and preimplantation genetic diagnosis.