More and more women are turning to nutritional supplements to increase their chances of becoming pregnant.
The leading cause of female infertility known today is ovulatory dysfunction, which accounts for about 25% of diagnoses. Approximately 70% of women with anovulation are affected by ovarian polycystosis or Pcos. This syndrome is a multifactorial disorder and is characterized by a combination of clinical alterations, such as anovulation and hyperandrogenism, biochemical, such as excessive concentrations of androgens and luteinizing hormone, and morphological, in the case of polycystic ovary. Although the etiology of Pcos is complex and controversial, the role of insulin resistance is a key etiologic component. Based on these premises, several nutrients have been proposed as novel therapeutic strategies for infertile patients with Pcos.
Endometriosis is a condition characterized by chronic gynecologic inflammation due to the presence of functional endometrial glands outside the uterine cavity. It affects 7-10% of women of reproductive age and up to 50% of women with infertility. Although the pathophysiologic mechanisms of endometriosis have not been fully elucidated, several data have shown that it is characterized by a systemic inflammatory pattern and an altered immune system. In addition, a pathogenetic role by environmental factors, including dietary habits and nutritional components, has been suggested. Since the development of endometriosis requires alterations in several biological pathways, several nutrients have been proposed as supplemental treatment for patients with endometriosis-associated infertility.
Idiopathic infertility identifies unexplained forms and occurs in 11% of infertile couples seeking IVF treatments. Although it is universally accepted that nutrition and lifestyle influence preconception reproductive performance, nutritional care is often inadequate. Recent studies have shown that women with idiopathic infertility often have undiagnosed dietary imbalances that can adversely affect fertility.
In order to increase the chances of pregnancy, many women require adjuvant treatments with dietary supplements. In a recent study conducted in women who were undergoing in vitro fertilization at a fertility center in the United Kingdom, 55% of them reported using some type of supplement with various ingredients. In addition, 16% of patients reported taking only folic acid. The total value of the European supplement market in 2019 reached €13.2 billion, with Italy being the largest market with a 27% share of the value. In 2019 alone, 28.6 million supplements were prescribed and the gynecological area reached 14% of all prescriptions. The rationale for use is to make up for a deficiency of nutritional substances or to ensure the optimal intake that can exert a positive effect on various fertility parameters, such as hormonal balance, ovulation, oocyte quality, embryo quality and probability of achieving a full-term pregnancy.
The most common ingredient is myo-inositol, contained in 87.5% of formulations. Inositols comprise a family of nine stereoisomers, of which myo-inositol and D-chiro-inositol are the most common isoforms in eukaryotic cells. These molecules participate in a multitude of biological functions, including: signaling pathways, reproductive function, and cell growth and survival.
In relation to female fertility, inositols have been shown to facilitate ovulatory processes through an insulin-sensitizing action. In addition, myo-inositol has been shown to exert a positive action on the in vitro maturation of rat oocytes, suggesting an ameliorative effect on oocyte quality and embryo development. In addition, a recent systematic review showed that daily use of 4 g of myo-inositol was effective in reducing chorionic gonadotropin administered to women undergoing in vitro fertilization. These data suggest that this molecule may have an ovarian sensitizing action toward gonadotropin. The levels of myo-inositol in the various formulations, were unsatisfactory. The minimum effective dose, or mED, of 4 g/day, was only guaranteed in 13.4% of cases. In the remaining supplements, the myo-inositol concentration was 2 g or even lower. D-chiro inositol was present in satisfactory amounts in four products and underdosed in four other formulations.
Folic acid was the second most common ingredient, included in 83% of the products evaluated. In four supplements, its dosage did not reach the mED of 400 mcg. This is relevant because the WHO recommends that all women of reproductive age should receive daily supplementation of 400 mcg of folic acid, in addition to consuming folate-rich foods, in order to prevent neural tube defects, so-called Ntd. In addition, peri-conception folic acid supplementation has been shown to reduce the incidence of non-Ntd birth defects, including cleft palate, limb reduction deficits, and genitourinary defects. Therefore, those supplements containing low doses of folic acid, less than 400 mcg/day, probably do not reduce the risk of Ntd and non-Ntd birth defects.
Vitamin D3 was included in about 30% of the supplements evaluated. It is a fat-soluble steroid hormone that underlies several autocrine, paracrine, and endocrine physiologic functions in the female reproductive system. This hormone modulates follicle recruitment through the regulation of anti-mullerian hormone secretion. In addition, this substance is involved in the regulation of ovarian and endometrial cell proliferation. However, serum levels of vitamin D in women undergoing in vitro fertilization do not seem to influence the outcome in clinical practice, and the effects of vitamin D3 supplementation on female fertility are still under evaluation.
Melatonin was contained in two supplements. Melatonin is a low-molecular-weight hormone that modulates multiple metabolic pathways in humans, including the regulation of certain biological rhythms, reproductive mechanisms, and immune pathways. With regard to female fertility, its supplementation has been shown to have a positive effect on oocyte and embryo quality and lutein function. For these reasons, it is currently considered as a promising molecule in the field of female infertility.
N-acetyl-cysteine, or Nac, has been included in one supplement. This molecule has strong antioxidant and mucolytic activities as well as insulin-sensitizing properties. For these reasons, Nac is commonly used as an adjuvant for the treatment of several pathological conditions, especially those affecting the lungs, heart and liver. In the gynecological field, it has been shown that an integration with Nac improves spontaneous ovulation, even in women with polycystic ovary syndrome, the quality of the oocyte and the embryo in infertile women undergoing in vitro fertilization.
CoenzymeQ10 is a powerful scavenger of free radicals and therefore acts as an antioxidant in mitochondria. These organelles play a crucial role in the regulation of energy metabolism and are the site of significant oxidative attacks. The CoQ10 plays an important role in the protection of female gametes from oxidative stress; in fact, its concentration in the follicular fluid is significantly lower in older women than in young ones. Supplementation with this molecule has been associated with an improvement in oocyte quality both in animals and in human studies, thus suggesting its potential role as an adjuvant in improving fertility in infertile women.
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