Dr Eliran

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Eliran Mor MD

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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 (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 (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.

 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 (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.