Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol’s family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.

A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected by an endocrine and metabolic issue. The term PCOS might not be appropriate to indicate the phenotypes described by the Rotterdam criteria, since the only phenotype with a gynecological issue alone is PCOS phenotype D. This novel perspective regarding how PCOS is currently defined leads the way to a reinterpretation of the entire pathological context and the treatment prescribed, such as inositols. A new point of view on the etiopathogenesis of the disease completely changes the current meaning of PCOS and consequently the therapeutic rationale evaluated to date.

Purpose: The study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment. Methods: A total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening. Results: VD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered. Conclusion: Supplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values. Trial registration number: 07/2018.

Background: The aim of the present study is to investigate the effects produced by a treatment with myo-Inositol (myo-Ins) in women presenting polycystic ovary syndrome (PCOS) of different phenotypes. Methods: We performed a retrospective study to evaluate whether patients presenting different PCOS phenotypes, treated for 6 months with myo-Ins, might exhibit a differential response to the treatment. On this premise, we clustered women with PCOS phenotypes A, B, and C in the first study group (hyperandrogenic PCOS or H-PCOS), and women presenting PCOS phenotype D in a separate study group (non-hyperandrogenic PCOS or NH-PCOS) to evaluate if the presence of hyperandrogenism, shared by H-PCOS, might imply a metabolic/endocrine condition rather than a gynecological issue. Results: The administration of myo-Ins induced a significant improvement in metabolic and endocrine parameters in H-PCOS, while the effects on NH-PCOS were negligible. Additionally, myo-Ins treatment improved the endometrial thickness of H-PCOS. Conclusions: Subjects selected for the study exhibited a differential response to myo-Ins therapy according to their PCOS phenotypes. The data suggest that the same treatment might not equally improve the parameters of the PCOS condition in each sub-group of patients. It is crucial to distinguish the various phenotypes to properly select the therapeutical approach.

Accumulating evidence suggests that oral supplementation with myo-Inositol (myo-Ins) is able to reduce the amount of gonadotropins and days of controlled ovarian hyperstimulation (COS) necessary to achieve adequate oocyte maturation in assisted reproduction technology (ART) protocols, particularly in women affected by polycystic ovary syndrome (PCOS). We used computational calculations based on simulation modellings. We simulated in vitro fertilization (IVF) procedures—with or without intracytoplasmic sperm injection (ICSI)—with 100,000 virtual patients, accounting for all the stages of the entire IVF procedure. A Monte Carlo technique was used to account for data uncertainty and to generate the outcome distribution at each stage. We considered virtual patients with PCOS undergoing IVF cycles to achieve pregnancy. Computational data were retrieved from clinical experience and published data. We investigated three parameters related to ART protocols: cost of single procedure; efficacy to achieve ongoing pregnancy at 12 gestational weeks; overall cost per single pregnancy. The administration of oral myo-Ins during COH protocols, compared to the standard COH with recombinant Follicle Stimulating Hormone (rFSH) only, may be considered a potential strategy to reduce costs of ART for the Italian Health System.

Background: The study aimed to evaluate the efficacy of a combination of Dioscorea villosa (containing diosgenin), vitamin D, and α-lactalbumin, in women with Polycystic Ovary Syndrome (PCOS) phenotype D. The primary objective was to investigate improvements in menstrual cycle regularity. Methods: A total of 24 women aged 22–34 years with PCOS phenotype D received daily supplementation with 600 mg Dioscorea villosa (120 mg diosgenin), 100 mg α-lactalbumin, and 50 μg vitamin D for six months. Clinical and biochemical assessments, including hormonal profiling and menstrual cycle monitoring, were conducted at baseline (T0), after 3 months (T1), and after 6 months (T2). Results: The treatment led to a statistically significant improvement in menstrual cycle regularity: eumenorrhea was achieved in 50% of patients at T2, compared to 0% at baseline. Significant changes were also observed in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH/FSH ratio, alongside a reduction in insulin and HOMA-index at T1. No adverse events were reported. Conclusions: The combination of Dioscorea villosa, vitamin D, and α-lactalbumin promotes menstrual cycle regularization in women with PCOS phenotype D. The positive result suggests a beneficial role of the treatment when administered to this specific subtype of PCOS and supports the use of targeted nutraceutical therapy as an alternative to conventional treatments, especially in non-hyperandrogenic PCOS patients.