Ospedale Filippo Del Ponte Varese

The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term "Endometriosis" (ID:D004715) with "Etiology" (ID:Q000209), "Immunology" (ID:Q000276), "Genetics" (ID:D005823) and "Epigenesis, Genetic" (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.

Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings suggest that HMO composition to be regulated time-dependently by an enzyme as well as substrate availability and that ppBMI, mode of delivery, and parity may influence maternal physiology to affect glycosylation marginally within the initital period of lactation. Our observational study is the largest European standardized and longitudinal (up to 4 months) milk collection study assessing HMO concentrations and basic maternal characteristics. Time of lactation and milk groups had the biggest impact on HMO variation. Future studies need to elucidate these observations and assess the physiological significance for the breastfed infant.

Iron needs increase exponentially during pregnancy to meet the increased demands of the fetoplacental unit, to expand maternal erythrocyte mass, and to compensate for iron loss at delivery. In more than 80% of countries in the world, the prevalence of anemia in pregnancy is > 20% and could be considered a major public health problem. The global prevalence of anemia in pregnancy is estimated to be approximately 41.8%. Undiagnosed and untreated iron deficiency anemia (IDA) can have a great impact on maternal and fetal health. Indeed, chronic iron deficiency can affect the general wellbeing of the mother and leads to fatigue and reduced working capacity. Given the significant adverse impact on maternal-fetal outcomes, early recognition and treatment of this clinical condition is fundamental. Therefore, the laboratory assays are recommended from the first trimester to evaluate the iron status. Oral iron supplementation is the first line of treatment in cases of mild anemia. However, considering the numerous gastrointestinal side effects that often lead to poor compliance, other therapeutic strategies should be evaluated. This review aims to provide an overview of the current evidence about the management of IDA in pregnancy and available treatment options.

The recent COVID-19 pandemic has spread to Italy with heavy consequences on public health and economics. Besides the possible consequences of COVID-19 infection on a pregnant woman and the fetus, a major concern is related to the potential effect on neonatal outcome, the appropriate management of the mother-newborn dyad, and finally the compatibility of maternal COVID-19 infection with breastfeeding. The Italian Society on Neonatology (SIN) after reviewing the limited scientific knowledge on the compatibility of breastfeeding in the COVID-19 mother and the available statements from Health Care Organizations has issued the following indications that have been endorsed by the Union of European Neonatal & Perinatal Societies (UENPS). If a mother previously identified as COVID-19 positive or under investigation for COVID-19 is asymptomatic or paucisymptomatic at delivery, rooming-in is feasible, and direct breastfeeding is advisable, under strict measures of infection control. On the contrary, when a mother with COVID-19 is too sick to care for the newborn, the neonate will be managed separately and fed fresh expressed breast milk, with no need to pasteurize it, as human milk is not believed to be a vehicle of COVID-19. We recognize that this guidance might be subject to change in the future when further knowledge will be acquired about the COVID-19 pandemic, the perinatal transmission of SARS-CoV-2, and clinical characteristics of cases of neonatal COVID-19.

Abstract Introduction Measurement of breath hydrogen (H 2 ) and methane (CH 4 ) excretion after ingestion of test‐carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline. Methods This consensus‐based clinical practice guideline defines the clinical indications, performance, and interpretation of H 2 ‐CH 4 ‐breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria. Results The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro‐cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H 2 ‐CH 4 ‐breath tests in these indications and recommends approaches to mitigate these issues. Conclusion This clinical practice guideline should facilitate pan‐European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.

BACKGROUND: Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. METHODS: All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. RESULTS: Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. CONCLUSIONS: Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Chronic endometritis (CE) is a poorly investigated pathology which has been related to adverse reproductive outcomes, such as implantation failure and recurrent miscarriage. In this paper, we aim to provide an overview of diagnosis, etiology, pathophysiology and treatment of CE, its impact on endometrial microenvironment and its association with infertility. We present a narrative review of the current literatures, synthesizing the findings retrieved from searches of computerized databases. CE is more prevalent in infertile patients. Effective antibiotic treatment of CE seems to improve the pregnancy and live birth rate in patients with unexplained recurrent pregnancy loss (RPL), and increase ongoing pregnancy rate in patients with recurrent implantation failure. In order to increase the diagnostic accuracy, immunohistochemistry is recommended besides the conventional histology. In addition, hysteroscopy could be considered as gold standard tool for diagnosis, considering its high correlation with histological findings. CE, as the chronic inflammation of endometrium, is usually asymptomatic and probably underestimated. Interaction of bacteria with endometrial microenvironment promotes changes in leukocyte population, cytokine production and growth factors which support its negative impact on endometrial receptivity. Nevertheless, standardization of the criteria for histopathological diagnosis and immunohistochemistry technique needs to be defined.

Endometriosis is an estrogen-dependent disease defined by the presence and growth of functional endometrial-like tissue, glands and stroma, outside the uterine cavity. Macrophages are broadly classified into pro-inflammatory M1 macrophages, and M2 macrophages, which have selective anti-inflammatory and pro-fibrotic activities and are able to induce immunotolerance and angiogenesis. Based on these elements, the aim of our study was to evaluate CD14+CD68+CD197+CD80+ M1 and CD14+CD68+CD163+CD206+ M2 macrophages in tissue samples from ovarian endometriomas of women affected by endometriosis at different stages of the disease. For each patient, we collected a biological sample of the cyst (ovarian endometriomas for cases and ovarian functional cyst for controls) during laparoscopy. We found that the number of both M1 and M2 macrophages was significantly higher in endometriosis group than controls, regardless of stage (p < .0001 for each stage versus controls). Moreover, our data analysis shows a trend in progressive decrease of M1 macrophages from stage I to stage IV; on the contrary, M2 macrophages show a specular trend compared to M1 macrophages, with a progressive increase from stage I to stage IV. This may contribute to the pro-inflammatory microenvironment in the early stages of the disease, and to the pro-fibrotic activity of the advanced stages.

The aim of this study is to analyse the changes in select gait parameters following anterior cruciate ligament (ACL) reconstruction. The study was performed on 15 subjects who underwent ACL reconstruction by the bone-patellar tendon-bone technique. Gait analysis was performed using the Elite three-dimensional (3D) optoelectronic system (BTS), a Kistler force platform and the Telemg telemetric electromyograph (BTS). Kinematic data were recorded for the principal lower limb joints (hip, knee and ankle). The examined muscles include vastus lateralis, rectus femoris, biceps femoris and semitendinosus. The results obtained from the operated subjects were compared with those of 10 untreated subjects and 5 subjects without ACL damage. In the operated subjects the knee joint angular values regained a normal flexion pattern for the injured limb during the stance phase. The analysis of joint moments shows: (a) sagittal plane: recovery of the knee flexion moment at loading response and during preswing; (b) frontal plane: recovery of the normal patterns for both hip and knee adduction-abduction moments during the entire stance phase. The examination of ground reaction forces reveals the recovery of frontal component features. The EMG traces show the normal biphasic pattern for the operated subjects as compared to the untreated subjects. The results suggest that the gait parameters shift towards normal value patterns.

Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

The advent of laparoscopy marked a fundamental change in the evolution of medicine. The procedure progressed consistently after the first time it was performed in a human being nearly a hundred years ago. The 1960's and 1980's witnessed groundbreaking changes. During this time, laparoscopy evolved from a purely diagnostic procedure into an independent surgical approach. Outstanding pioneers of the times were Palmer, Frangenheim and Semm. Laparoscopy advanced rapidly and influenced gynecology as well. The procedure was initially attacked most vociferously by the surgical fraternity. However, within a short period of time the pendulum shifted: laparoscopy became the preferred surgical approach for a variety of diseases-whether benign or malignant-in several medical disciplines. Laparoscopy has become a routine approach in the twenty-first century. Technical advancements have led to robot-assisted surgery. Future developments will include artificial intelligence and augmented reality. In the present article we address past milestones, current practices, and future challenges in laparoscopy.

We investigated menstrual irregularities after the first and second doses of the COVID-19 vaccine. Women answered a customised online questionnaire (ClinicalTrial.gov ID: NCT05083065) aimed to assess the vaccine type, the phase of the menstrual cycle during which the vaccine was administered, the occurrence of menstrual irregularities after the first and second doses, and how long this effect lasted. We excluded women with gynaecological and non-gynaecological diseases, undergoing hormonal and non-hormonal treatments, in perimenopause or menopause, as well as those who had irregular menstrual cycles in the last 12 months before vaccine administration. According to our data analysis, approximately 50-60% of reproductive-age women who received the first dose of the COVID-19 vaccine reported menstrual cycle irregularities, regardless of the type of administered vaccine. The occurrence of menstrual irregularities seems to be slightly higher (60-70%) after the second dose. Menstrual irregularities after both the first and second doses of the vaccine were found to self-resolve in approximately half the cases within two months. Based on these results, we suggest to consider these elements during the counselling of women who receive the COVID-19 vaccine, letting them know about the potential occurrence of temporary and self-limiting menstrual cycle irregularities in the subsequent month(s).

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

The latest scientific acquisitions are demonstrating what has already been hypothesized for more than twenty years about the development of the state of health/illness of individuals. Indeed, certain stimuli, if applied to a sensible phase of development, are able to modify, through epigenetic mechanisms, gene expression of DNA, resulting in adaptive modifications of phenotype to the environment, which may reflect negatively on the health of every individual. This concept, applied to nutrition, has opened up important prospects for research in this area. The nutritional history of an individual, linked to the development of a healthy state, would begin very early. In fact, since the pregnancy and for the next two years (for a total of about 1000 days), the maternal eating habits, the type of breastfeeding and then the main stages of nutrition in the evolutionary phase represent those sensitive moments, essential for the development of important endocrine, metabolic, immunological alterations, better known as metabolic syndrome. This condition would represent the physiopathogenetic basis for explaining a series of disorders, known as non communicable diseases (NCDs) such as obesity, diabetes, hypertension, cardiovascolar disease and all those conditions that today affect the health of most industrialized countries and through the years are emerging especially in developing countries (South America, Asia), where new environmental conditions and increased food availability are changing food habits, with far-reaching public health impacts. This paper analyzes these new nutritional perspectives and the main implications of what has been termed the 1000-day theory.

OBJECTIVE: Being overweight or obese is one of the most common reasons that children and adolescents are teased at school. We carried out a study in order to investigate: i) the relation between weight status and school bullying and ii) the relation between weight status categories and types of victimization and bullying in an outpatient sample of Italian children and adolescents with different degrees of overweight from minimal overweight up to severe obesity. PARTICIPANTS/METHODS: Nine-hundred-forty-seven outpatient children and adolescents (age range 6.0-14.0 years) were recruited in 14 hospitals distributed over the country of Italy. The participants were classified as normal-weight (N = 129), overweight (N = 126), moderately obese (N = 568), and severely obese (N = 124). The nature and extent of verbal, physical and relational bullying and victimization were assessed with an adapted version of the revised Olweus bully-victim questionnaire. Each participant was coded as bully, victim, bully-victim, or not involved. RESULTS: Normal-weight and overweight participants were less involved in bullying than obese participants; severely obese males were more involved in the double role of bully and victim. Severely obese children and adolescents suffered not only from verbal victimization but also from physical victimization and exclusion from group activities. Weight status categories were not directly related to bullying behaviour; however severely obese males perpetrated more bullying behaviour compared to severely obese females. CONCLUSIONS: Obesity and bullying among children and adolescents are of ongoing concern worldwide and may be closely related. Common strategies of intervention are needed to cope with these two social health challenges.

The authors declare that there is no conflict of interest.

BACKGROUND: Late preterm infants account for the majority of preterm births. They are at an increased risk of neonatal mortality and morbidity and are less likely to initiate breastfeeding and to be exclusively breastfed at discharge compared to infants born at term. The aim of this study was to identify the facilitators and barriers to breastfeeding during hospital stays according to the experiences of mothers of late preterm infants. METHODS: We conducted a cross-sectional questionnaire survey. Mothers who intended to breastfeed and had given birth to a newborn admitted to level I and II care, with a gestational age of 34 0/7 to 36 6/7 weeks, were enrolled. Sociodemographic data, neonatal variables, mode of feeding and feeding status at discharge were also collected. RESULTS: A total of 92 mothers who had given birth to 121 infants were enrolled. At discharge, any human milk was fed to 94 % of infants, with exclusively human milk being fed in 43 % of cases; exclusively formula was fed to 6 % of infants. In the multivariate analysis, having expressed breast milk was independently associated with an increased risk of being fed with either any human milk or formula only (OR = 2.73, 95 % CI 1.05-7.1, p = 0.039), whereas being encouraged to practice kangaroo mother care tended to have a protective effect (OR = 0.46, 95 % CI 0.2-1.06, p = 0.07). CONCLUSIONS: Based on the present findings, health care professionals should strive to fully implement breastfeeding support for mothers of late preterm infants who intend to breastfeed, in particular optimizing breast milk expression and promoting kangaroo mother care. Further studies are needed to gain further insight into the complex interplay of the factors that modulate breastfeeding outcome in late preterm infants.

BACKGROUND: To identify obstetric risk factors for de novo pelvic floor disorders after vaginal delivery. METHODS: Antenatally asymptomatic women who delivered vaginally were interviewed on urinary, anal and sexual disorders antenatally, 6 and 12 months postpartum. RESULTS: Of 967 women, 336 were included for final analysis. Urinary symptoms occurred in 27 and 23% of women at 6 and 12 months postpartum: univariate analysis showed a significant relation to the use of epidural analgesia (p =0.04) and to a second stage of labour >1 h (p =0.02), the latter was confirmed significant by multivariate analysis. Anal incontinence occurred in 7.1 and 6.8% of women at 6 and 12 months postpartum, respectively. Dyspareunia was reported by 24% at 6 months, decreasing to 8% at 12 months (p <0.0001). CONCLUSIONS: Our study shows that a second stage longer than 1 h is associated with the development of postpartum urinary incontinence. Except for dyspareunia, pelvic floor dysfunction rarely resolves spontaneously.

Polycystic ovary syndrome (PCOS) is a heterogenous disorder characterized by chronic ovulation dysfunction and hyperandrogenism. It is considered the most common endocrinological disorder, affecting up to 25% of women of reproductive age, and associated with long-term metabolic abnormalities predisposing to cardiovascular risk, such as insulin resistance (IR), dyslipidemia, endothelial dysfunction, and systemic inflammation. PCOS is also characterized by elevated serum levels of luteinizing hormone (LH), causing a condition of hyperandrogenism and a consequent altered ratio between LH and the follicle stimulating hormone (FSH). Over the years, several different approaches have been proposed to alleviate PCOS symptoms. Supplementation with natural molecules such as inositols, resveratrol, flavonoids and flavones, vitamin C, vitamin E and vitamin D, and omega-3 fatty acids may contribute to overcoming PCOS pathological features, including the presence of immature oocyte, IR, hyperandrogenism, oxidative stress and inflammation. This review provides a comprehensive overview of the current knowledge about the efficacy of natural molecule supplementation in the management of PCOS.