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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 (É·-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 (1, 2). 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 (3, 4). According to the WHO, infertility may affect ∼80 million women worldwide (5). 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 (6). 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 (7, 8).
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 (9). 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 (9–12). 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 (11, 13). 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 (14).
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.
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 (15). In this section, we compared 2 different nutritional approaches which differently affect both female and male fertility.
EliranAs 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 (5, 15). 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 (16).
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 (16). Moreover, studies show that healthy dietary patterns can also increase the chances of live birth among women using assisted reproductive technology (ART) (17, 18). In a large cohort study by Chavarro et al. (19) 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. (20) 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 (21). 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 (22).
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 (23, 24).
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 (25). 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 (26). 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 (27).
It has been shown that a diet with a high glycemic index and rich in animal protein, TFAs, and SFAs may negatively affect fertility (5). 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.
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 (15, 33).
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 (5). 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 (34). 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 (33). The main sources of added sugars are carbonated beverages, which can negatively affect fertility (35). Moreover, Machtinger et al. (36) 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 (37).
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 (38) 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 (39) 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. (40) 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 (41). 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 (42). 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) (42, 43).
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 (39, 44–47). 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 (48). 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 (39). 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 (40). 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 (49). 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 (44).
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 (50, 51). 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 (40, 51, 52). 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 (39, 43, 53–56). 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 (57). 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 (58). Nevertheless, further investigations among women with a diminished ovarian reserve are critical. Nassan et al. (59) 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. (60), 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 (61).
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 (62) and concentration in plasma (53) 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. (63), 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 (64, 65). On the other hand, Wise et al. (66) 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 (67). Additionally, women consuming >4 portions of dairy daily during adolescence presented a 32% lower risk of endometriosis during adulthood than women consuming ≤1 portion (68). Moreover, the total dairy intake was positively associated with live birth among women aged ≥35 y (69).