Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. METHODS: A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. RESULTS: Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. CONCLUSION: The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

The role of antioxidant vitamins in hypertensive disorders of pregnancy.

Preeclampsia (PE) is an important and a leading cause of both maternal morbidity and adverse perinatal outcomes. Despite progress in perinatal medicine for patients with an established diagnosis of PE, a therapeutic approach other than termination of pregnancy was unsuccessful. Women predisposed to PE begin pregnancy with a certain degree of endothelial dysfunction, a lesion that precedes shallow placentation. The proposed sequence of events comprises endothelial dysfunction, defective trophoblast invasion, and consequential impaired placental perfusion, immune maladaptation and inflammation. The possible link between these could be oxidative stress by excessive production of reactive oxygen species coupled with inadequate or overwhelmed antioxidant defense mechanisms. These defense mechanisms, involving antioxidant vitamins and enzyme systems, may restrain the extent of damage caused by oxidative stress. Markers of oxidative stress in women with established PE were confirmed. Accordingly, these findings support an expected beneficial effect of antioxidant therapy in the prevention of PE and other pregnancy-related disorders. Numerous studies have been carried out in order to investigate this possible and simple prophylactic and/or therapeutic approach in prevention of oxidative stress and eventual reduction of PE and its perinatal complications. In this review the role of vitamin antioxidants in prevention and treatment of PE is discussed. Despite the logic behind using antioxidant vitamins, the data, thus far, are at best conflicting.

Micronutrients in women's reproductive health: I. Vitamins.

Proper nutritional status of women before, during, and after pregnancy is an important element of reproductive health. It maintains maternal health and reduces the risk of adverse pregnancy outcome, birth defects and chronic disease in children later in postnatal life. Pregnancy creates a special metabolic demand for high-quality nutrients. With careful food selection, it is possible to obtain most of the recommended levels of nutrients. Apart from the dietary intake, nutrition is highly dependant on economic status, social and cultural environment, and personal habits of the mother. Nutritional imbalance could cause detrimental effects to the pregnant woman, influence pregnancy outcome, and impair breast milk composition. Despite the extensive research, we still do not have a complete understanding how nutritional status of the mother influences her health as well as fetal growth and development. It is well known that fetal growth and development is strongly linked with maternal supply of essential nutrients, e.g. vitamins. The exact role of the variety of micronutrients in fetal growth and development has yet to be explored in detail. It is estimated that up to 30% of pregnant women suffer from a vitamin deficiency. Without supplementation, about 75% would show a deficit of at least one vitamin. Moreover, multivitamin deficit combinations often co-exist, and subclinical depletations are probably common; consequences could be severe. Studies carried on in developing countries have shown that improving micronutrient intake in deficient women can reduce maternal morbidity and mortality. Also, proper maternal intake of important micronutrients directly enhances the quality of breast milk. To meet the increasing demands during pregnancy and the breastfeeding period women should not be dependent only upon the dietary intake: adequate reserve is essential for the successful pregnancy outcome.

Micronutrients in women's reproductive health: II. Minerals and trace elements.

It is widely accepted that micronutrients have a major function in many periods of women's life, particularly during pregnancy and lactation. Inadequate stores or intake of micronutrients might have adverse effects both to the mother (hypertension, anemia, complications of labor) and the fetus (congenital malformations, pre-term delivery, intrauterine growth retardation). The effect of improper nutrition is influenced by gestational age, severity of deficiency, or both. Generally, the daily requirements in minerals and trace elements are easily met in women having a balanced diet. Such diet during pregnancy should provide the recommended daily allowance of all nutrients except elemental iron. Consequently, deficiency states are supposed to be rare in developed countries, and supplementation should be made on an individual basis. On the other hand, nutritional deficiencies during pregnancy might be difficult to detect. Studies from developing countries where micronutrient malnutrition is common during pregnancy gave us strong evidence that supplementation of certain trace elements and minerals could prevent some of the most severe adverse pregnancy outcomes. While some micronutrients have been studied extensively (e.g. calcium, iron, zinc, iodine), much less is known about others. It has been shown that multiple micronutrient deficiencies, rather than single deficiencies, are common. Our knowledge about the significance of interactions between micronutrients in relation to pregnancy outcome is limited. The role of these interactions in improving pregnancy outcome need to be investigated more precisely. According to the summarized data, the potential benefits of routine supplementation seem to outweigh any potential adverse reaction that can be attributed to their consumption.