Polycystic ovary syndrome (PCOS) is a common endocrine disorder amongst reproductive-aged women associated with cardiometabolic, reproductive and psychological abnormalities. Lifestyle modification, including a healthy diet, is considered first-line treatment for management of clinical symptoms. However, there is limited high-quality evidence to support one superior therapeutic dietary intervention for PCOS management that is beyond general population-based dietary guidelines. Adherence to a Mediterranean diet (MedDiet) has been shown to decrease cardiometabolic disease risk and attenuate depressive symptoms, particularly in patients with metabolic perturbations. This narrative review summarises the proposed biological mechanisms underpinning the potential therapeutic benefits of a MedDiet for the management of cardiometabolic, reproductive and psychological features related to PCOS. Observational evidence suggests an inverse relationship between MedDiet adherence and PCOS features, particularly insulin resistance and hyperandrogenemia. Although the exact mechanisms are complex and multifaceted, they are likely related to the anti-inflammatory potential of the dietary pattern. These mechanisms are underpinned by anti-inflammatory bioactive constituents present in the MedDiet, including carotenoids, polyphenols and n-3 polyunsaturated fatty acids (PUFAs). Synthesis of the available literature suggests the MedDiet could be a promising therapeutic dietary intervention to attenuate short and long-term symptoms associated with PCOS and may aid in reducing the longer-term risks associated with cardiometabolic diseases and reproductive and psychological dysfunction. Nevertheless, current evidence remains insufficient to inform clinical practice and well-designed clinical trials are needed. As such, we provide recommendations for the design and delivery of future MedDiet interventions in women with PCOS, including exploring the acceptability, and feasibility to enhance adherence.

Polycystic ovary syndrome (PCOS) is a complex reproductive and endocrine disorder affecting 5–10% of women of reproductive age, but the pathophysiology of PCOS still remains unknown. Here, the aim of our study was to analyze the effects of rapamycin treatment that may regulate impaired hormonal levels and folliculogenesis in dehydroepiandrosterone (DHEA)-treated PCOS mouse. We hypothesized that rapamycin may ameliorate the negative effects of PCOS in DHEA-induced PCOS mouse model. The target of rapamycin (TOR) gene product is a serine/threonine kinase that has been implicated in the control of cell growth, proliferation and autophagy, and rapamycin is a potent inhibitor of mTORC1 pathway. In this study, for the first time, mTORC1 and activation products are presented at protein and mRNA levels after rapamycin treatment in DHEA-induced PCOS mouse ovary. We showed that rapamycin treatment may regulate follicular development, hormonal levels and provide ovulation in DHEA-induced PCOS mouse. Additionally, we assessed decreased primordial follicle reserve, increased number of primary and secondary follicles, corpus luteum structure forms again after 10 days of rapamycin treatment. This study presented here suggests rapamycin treatment regulates hormonal phenotype and folliculogenesis in the ovary and also mTOR signalling pathway in granulosa cells of DHEA-induced PCOS mouse ovary which may have potential to attenuate understanding the mechanism of dominant follicle selection and anovulatory infertility.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age, associated with increased risks of metabolic disorders, depression and reduced quality of life. This study examined the impact of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on mental health, PCOS-related quality of life (PCOSQ), anthropometric indices, hirsutism, and metabolic/hormonal parameters in women with PCOS. Total of 52 women with PCOS, aged between 18 and 45 years, were randomly assigned to either the low calorie MIND diet group or the control group. Anthropometric data, depression and anxiety scores, serum levels of gonadotropins (luteinizing hormone [LH], follicle-stimulating hormone [FSH]), PCOSQ, and Ferriman-Gallwey score were evaluated before and after the intervention. Outcomes were assessed at baseline and at the end of the 8-week follow-up period. After 8 weeks, the MIND diet significantly reduced depression (β –3·03; 95 % CI: [–5·36, –0·70]; P = 0·011) and anxiety (β –3·54; 95 % CI: [–6·60, –0·49]; P = 0·024) scores compared with the control group. The MIND diet group exhibited significant increases in the emotion (β 0·63; 95 % CI: [0·18, 1·08]; P = 0·007) and body hair (β 0·65; 95 % CI: [0·03, 1·28]; P = 0·04) domains of the PCOSQ compared to the control group. The changes in other parameters did not show significant differences between the two groups. Both the MIND diet and control groups showed improvements in weight and BMI, with a slight advantage for the MIND diet group. These findings suggest that the MIND diet may be beneficial for improving mental health and some aspects of PCOSQ in women with PCOS.

Polycystic ovary syndrome is associated with increased risks for certain metabolic disorders such as insulin resistance, non-alcoholic fatty liver disease and suppressed ovarian follicular development. This study aimed to examine whether soya isoflavones (ISF) mitigate these polycystic ovary syndrome-associated metabolic disorders in a rat model. Weanling Sprague-Dawley female rats were randomly divided into six groups and were treated with either 0 or 83 µg/d dihydrotestosterone (DHT) to induce polycystic ovary syndrome and fed diets containing 0, 0·5, or 1 g ISF/kg diet for 8 weeks. DHT treatment increased food intake, body weight gain (P < 0·001), percentage of primordial follicles (60 % v. 50·9 %, P < 0·05) and accumulation of lipid droplets in the livers. It also elevated serum total cholesterol, free cholesterol, TAG, NEFA and leptin and hepatic total cholesterol and NEFA. Additionally, DHT treatment reduced the percentage of primary follicles (13·8 % v. 30·2 %, P < 0·05), ovary weight and length (P < 0·001), as well as insulin sensitivity (P < 0·01) compared with the Control. ISF intake at 1 g/kg reduced body weight gain, serum total cholesterol, free cholesterol, NEFA, leptin and hepatic TAG and DHT-induced insulin resistance (P < 0·01). ISF intake at both levels decreased DHT-induced lipid droplet accumulation in the livers and changes in the percentages of primordial and primary follicles. Dietary soya ISF alleviated DHT-induced body weight gain, insulin resistance and hepatic lipid droplet accumulation, as well as suppressed ovarian follicular development. This suggests that the consumption of soya foods or ISF supplements may be beneficial for individuals with polycystic ovary syndrome, mitigating the associated metabolic disorders such as diabetes and non-alcoholic fatty liver disease.

Polycystic Ovary Syndrome (PCOS) is a common hormonal condition affecting women of reproductive age(1). Women with PCOS experience a broad range of clinical symptoms, collectively grouped into reproductive, metabolic, psychological and anthropometric features(2). Complementary therapies, such as nutrient supplementation, have been identified as potential adjunct therapeutic approaches to support currently recommended lifestyle and pharmacological interventions(3). However, evidence for their overall efficacy and safety is inconsistent and unclear. This review aimed to systematically map the available literature on the use of nutrient supplementation for the management of PCOS features, including metabolic, reproductive, psychological and anthropometric. This review followed a systematic approach with literature searches using CINHAL, Cochrane reviews, Medline, PsycINFO, Scopus and LILACS conducted up to April 2022. All types of study designs were included if they reported on the efficacy or association between micronutrient supplementation and/or nutraceuticals on features of PCOS in women (≥ 18 years) with a confirmed diagnosis of PCOS. A total of 317 articles were included involving n = 23,926 women. Forty-three different supplements examined various clinical features of PCOS grouped into metabolic, reproductive, psychological and anthropometric. The most studied supplements included Inositols (n = 83), Vitamin D (n = 51), N-acetylcysteine (n = 25), Omega-3 fatty acids (n = 18) and Biotics (n = 14). Most studies (n = 262; 83%) reported on reproductive features followed by metabolic (n = 212; 66%), anthropometric (n = 181; 57%) and psychological (n = 5; 2%). Less than half (n = 148; 47%) of the included studies reported on the potential for adverse events. Our results highlight that the potential therapeutic benefit of micronutrient and nutraceutical supplementation on psychological features of PCOS warrants future exploration. Additional primary studies that are adequately powered are needed to investigate therapeutic doses needed for clinical benefits. Lastly, a more rigorous approach to monitoring and recording adverse event data is recommended.

People with polycystic ovary syndrome (PCOS) have higher weight gain and psychological distress compared to those without PCOS(1). While COVID-19 restrictions led to population level adverse changes in lifestyle, weight gain and psychological distress(2), their impact on people with PCOS is unclear. The aim of this study was to investigate the impact the 2020 COVID-19 restrictions had on weight, physical activity, diet and psychological distress for Australians with PCOS. Australian reproductive-aged women participated in an online survey with assessment of weight, physical activity, diet and psychological distress. Multivariable logistic and linear regression were used to examine associations between PCOS and residential location with health outcomes. On adjusted analysis, those with PCOS gained more weight (2.9%; 95% CI; 0.027–3.020; p = 0.046), were less likely to meet physical activity recommendations (OR 0.50; 95% CI; 0.32–0.79; p = 0.003) and had higher sugar-sweetened beverage intake (OR 1.74; 95% CI 1.10–2.75; p = 0.019) but no differences in psychological distress compared to women without PCOS. People with PCOS were more adversely affected by COVID-19 restrictions, which may worsen their clinical features and disease burden. Additional health care support may be necessary to assist people with PCOS to meet dietary and physical activity recommendations.

Polycystic Ovary Syndrome PCOS is an endocrine disorder affecting 8 to 13% of reproductive aged women(1). Dietary and physical activity changes are the first-line therapy to assist with symptom and weight management and to reduce the risk of reproductive, metabolic and psychological comorbidities(2). However, women with PCOS have a higher weight, experience weight gain, and a higher prevalence of living in a larger body. Health care professionals (HCPs) play a crucial role in delivering diet and physical activity advice for people with PCOS. Thus, the aim of this systematic review is to understand the barriers, facilitators, experiences, and perceptions of engagement and compliance with diet and physical activity modifications in people with PCOS and in HCPs providing or referring people with PCOS to diet and physical activity modifications. A mixed-method systematic review was conducted with quantitative studies narratively synthesised and all studies thematically analysed. There were 68 eligible papers, including n = 59 (n = 5198) people with PCOS and n = 17 (n = 2,622) HCPs. Several themes were identified as impacting people with PCOS’ ability to make diet and physical activity changes. HCP education on PCOS management through diet and physical activity was viewed by HCPs and people with PCOS to be inadequate, further impacting the quality of care and health outcomes. Dietary and physical activity advice delivered by a multidisciplinary team, including dietitians, was identified as a key component for change. Both people with PCOS and HCPs agreed that there was a need for individualised and PCOS-specific diet and physical activity advice. However, HCPs viewed that there was limited evidence supporting these recommendations and a lack of time to deliver this care. Weight stigma was identified as impacting both those in larger and smaller bodies with PCOS, reducing the quality of care and affecting self-perception and mental health. People with PCOS perceived that diet and physical activity are overly focused on weight loss and fertility, independent of their own personal motivations and goals. Systemic changes, including receiving diet and physical activity advice that meet the individual’s needs, are necessary for leading to long-term sustainable changes and improvements in health outcomes. A multidisciplinary team approach and an overhaul of HCPs’ perceptions and mentality of weight and weight-centric care for those with PCOS are essential in delivering effective diet and physical activity advice.

In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.

This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8–12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5–10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.

In recent years, obesity is a growing pandemic in the world and has likely contributed to increasing the incidence of obesity-related diseases. Fat mass and obesity-associated gene (FTO) is the first gene discovered which has a close connection with fat. Recent studies suggested that FTO gene has played an important role in the molecular mechanisms of many diseases. Obesity is considered to be a hereditary disease and can evoke many kinds of diseases, including polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), cancer, etc., whose exact possible molecular mechanisms responsible for the effect of FTO on obesity and obesity-related diseases remain largely unknown. In this review, we comprehensively discuss the correlation between FTO gene and obesity, cancer, PCOS, T2DM, as well as the molecular mechanism involved in these diseases.

Although the role of myo-inositol (MYO) in promoting the oocyte quality of PCOS patients has been documented in human studies; the cellular effects of this supplement on oocytes have not been directly examined due to ethical limitations. In the first phase of this study, MYO dosimetry was carried out simultaneously with the PCOS model development. An effective dose was obtained following the assessment of fasting insulin and testosterone levels using ELISA and ovarian morphology appraisal by histopathology. In the second phase, following the continuous administration of the effective dose of MYO and dehydroepiandrosterone (DHEA), cellular evaluation was performed. The quality of oocytes from superovulation was analyzed by examining maturity and normal morphology percentage using a stereomicroscope, intracellular reactive oxygen species (ROS) and glutathione (GSH) levels using fluorometry, and ATP count evaluation using ELISA. The results revealed that, among the four different MYO concentrations, the 0.36 mg/g dose compared with the DHEA group reduced testosterone levels and large atretic antral follicles (LAtAnF) diameter. This dose also increased the corpus luteum count and the granulosa:theca (G/T)layer thickness ratio in antral follicles. Furthermore, this dose increased mature oocytes and normal morphology percentage, ATP count, and GSH levels; however, it decreased ROS levels in mature oocytes. Our findings provide the grounds for further cellular and molecular studies on the PCOS mouse model, suggesting that the improvement in mitochondrial function and its antioxidant properties is probably one of the mechanisms by which MYO increases oocyte quality.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases characterised by unusual levels of sex hormones and dysfunction of the ovaries. The infertility rate is high among patients with PCOS. Unusual hormonal status can lead to the inability of ovaries to release functional and mature follicles. Clinical trials on the effects of N-acetylcysteine (NAC) supplementation on ovulation and sex hormones profile in women with PCOS have been controversial. We performed a systematic review and meta-analysis to evaluate the potential effects of NAC supplementation on ovulation and sex hormones profile. PubMed, Scopus, Embase, Web of Science and Cochrane Central library international databases were searched till September 2021. Meta-analysis was performed using a random-effects approach in case of significant between-study heterogeneity. Eighteen studies, including 2185 participants, were included in the present meta-analysis. NAC significantly reduced total testosterone (TT) levels (standardised mean difference (SMD): −0·25 ng/ml; 95 % CI (−0·39, −0·10); ‘P < 0·001’, I 2 = 53·9 %, P = 0·034) and increased follicle-stimulating hormone (FSH) levels (SMD: 0·39 mg/ml; 95 % CI (0·07, 0·71); P = 0·01, I 2 = 70·9 %, P = 0·002). Oestrogen levels also increased after correcting publication bias. However, no significant effect was observed on the number of follicles, endometrial thickness, progesterone, serum luteinising hormone levels and sex hormone-binding globulin. The results indicated that NAC supplementation decreased TT levels and increased FSH levels. Overall, NAC supplementation might be effective in the improvement of reproductive system function in patients with PCOS.

Polycystic ovary syndrome (PCOS) is a complex disorder and genetic factors are believed to play a role. The main aim was to investigate expression levels of genes involved in PI3K/AKT signalling pathway pretreatment and post-treatment. Mouse models of PCOS were generated. Group one included control mice with no polycystic ovaries (n = 4), Group 2 included a PCOS mouse model (n = 8), Group 3 included PCOS mice treated with clomiphene citrate (n = 7) and Group 4 included PCOS mice treated with clomiphene citrate, metformin and pioglitazone (n = 8). Histochemical analyses were performed. Total RNA was extracted and cDNA was synthesized. Irs, Akt1 and Akt2, mTor and Pdpk1 gene expression levels were evaluated by RT-PCR amplification. In Group 1, cortex and medulla were evaluated as normal; in Group 2, ovarian cortex was composed of immature oocytes and cystic follicles with atretic follicles. In Groups 3 and 4, follicles were in the process of normal follicle differentiation. The expression levels of Akt1 and Pi3k were significantly different (P < 0.0001) between Groups 1 and 2. The significant differences in expression levels of Pi3k and Akt1 were also observed between the Group 1 and both Groups 3 and 4 (P < 0.0001). Furthermore, significant variations of the expression levels of mTor between Groups 1 and 4 were observed. The extrapolation of results of this study may imply that follicular development may be regulated by molecular pathways involving Pi3k, Akt1 and mTor expression. Therefore, genes in the PI3K/AKT pathway may have a direct regulatory role in the development of PCOS.

Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

Intake of resveratrol has been associated with improved ovarian morphology under in vitro and in the animal models; however, this finding has not been confirmed in trials. The aim of our study was, therefore, to use a placebo-controlled approach with the detailed assessment of the ovarian morphology by applying transvaginal ultrasound to examine the effectiveness of this therapeutic approach in this group of women. The mean age of all participants was 28·61 (sd 4·99) years, with the mean BMI of 28·26 (sd 5·62) kg/m2. Resveratrol therapy, as compared with placebo, was associated with a significantly higher rate of improvement in the ovarian morphology (P = 0·02). Women who received resveratrol had a more dominant follicle than those getting placebo, with a significant reduction in the ovarian volume (P < 0·05). However, the number of follicle count per ovary (FNPO), stromal area (SA), ovarian echogenicity and distribution of follicles were not significantly altered (P > 0·05). Forty-one women with polycystic ovary syndrome (PCOS) were randomly assigned (1:1) to 3 months of daily 1000 mg resveratrol or placebo. Random assignment was done by blocked randomisation. Our primary endpoints were the change in the ovarian volume, SA and antral FNPO from the baseline to 3 months. Secondary endpoints were improvement in the distribution of follicles and ovarian echogenicity. Differences between the resveratrol and control groups were evaluated by Chi-square, Fisher’s exact test and repeated-measures ANOVA. Treatment with resveratrol significantly reduced the ovarian volume and polycystic ovarian morphology, thus suggesting a disease-modifying effect in PCOS.