Polycystic Ovary Research Articles

A CASE STUDY- AN AYURVEDA APPROACH ON POLYCYSTIC OVARIAN SYNDROME

A woman is the best and most precious creation of God. Women’s bodies undergo significant changes through-out their lives, leading to differences in health concerns for varying age groups. The reproductive cycle signifi-cantly affects in every stage of a woman’s life during the transition from a girl to a woman and a woman to a mother. PCOS is the most challenging lifestyle disorder that can affect women’s Multiple system and require a comprehensive perspective on health care for effective treatment. Metabolic derangement and associated com-plications include insulin resistance and diabetes, hyperlipidemia, fatty liver, hypertension, and sleep apnoea. Reproductive complications include oligomenorrhoea /amenorrhea, sub-fertility, endometrial hyperplasia, and cancer. Associate psychological concerns include depression and disordered eating. Additionally, cosmetic is-sues are hirsutism, androgenic alopecia, and acne. This particular feminine disorder is not described word for word in Ayurveda. Ayurveda literature is under the broad heading of Yoni vyapad, Artava dustya, and Artava kshaya. Analyzing the signs and symptoms of diseases, it can be assumed that vitiated Kapha causes Sroto-rodha (blockage of channels), resulting in Vata vaigunya. Agneya property of pitta depleted. Here is a case re-port of 25 a 25-year-old female patient who presented with irregular menstruation, rapid weight gain, and de-pression. On Ultrasonography, she has detected a bilateral polycystic ovary. Depending upon the clinical fea-tures, the patient was given Aampachan. Vatanuloman, Kaphavata hara, Medohara, and Artavajanana proper-ties of medicines and yoga. After almost three and half months of internal medicine, symptoms reduced marked-ly, and menstruation was normal.

The waist-to-height ratio is a good predictor for insulin resistance in women with polycystic ovary syndrome

ObjectiveThis study aimed to explore the role of the waist-to-height ratio (WHtR) in assessing insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS).Materials and methodsWe enrolled 882 PCOS-afflicted women in a cross-sectional analysis to evaluate the association of the WHtR with IR. Their demographic characteristics, anthropometric parameters, and fasting blood samples were collected and measured. Moreover, IR was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). We estimated the relationship between the WHtR and IR and the cut-off thresholds of the WHtR for IR using multivariable linear regression and logistic regression models, respectively.Result(s)The prevalence rate of IR was 51.9%. The patients with PCOS and IR displayed significantly increased values for body mass index (BMI), waist circumference (WC), WHtR, systolic blood pressure (SBP), diastolic blood pressure (DBP), free androgen index (FAI), HOMA-IR, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB). However, the patients with PCOS and IR showed a reduction in estradiol (E2), luteinizing hormone (LH), LH/FSH ratio, sex hormone binding globulin (SHBG), and high-density lipoprotein (HDL-C) values than those without IR. Moreover, BMI (log-transformed), WC, and HOMA-IR (log-transformed) were positively correlated with the WHtR. When adjusting for potential confounding variables, the WHtR was significantly associated with HOMA-IR (log-transformed), with a standardized regression coefficient of 0.271. Furthermore, the WHtR was significantly associated with an increased risk of IR, with the adjusted odds ratio (OR) of 3.15 (WHtR multiplied by 10). Additionally, the WHtR helped to identify IR in women with PCOS with an optimal cut-off point of 0.519 (Youden index = 0.433).Conclusion(s)The WHtR had a positive association with IR in women with PCOS. Hence, we suggest that the WHtR, as a simple, practical, and reliable anthropometric measure, can be used to predict the risk of IR in patients with PCOS.

Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.

Impact of energy balance on polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of repro­duc­tive age , affecting one in five women worldwide . Overweight and obesity increase the prevalence of PCOS, which together with dyslipidemia is con­si­dered to be the dominant feature in 40 to 60% of cases. Diagnostic criteria include irregular menstrua­tion, androgen excess, and/or polycystic ovaries, with long-term consequences being hyperinsu­line­mia and infertility. Many studies suggest that met­formine and oral contraceptive combinations are com­monly prescribed to alleviate reproductive com­plaints; However, for overweight and obese patients planning pregnancy, weight loss of 5 to 10% through lifestyle modification is recommended as first-line treatment .

A Ketogenic Diet Followed by Gradual Carbohydrate Reintroduction Restores Menstrual Cycles in Women with Polycystic Ovary Syndrome with Oligomenorrhea Independent of Body Weight Loss: Results from a Single-Center, One-Arm, Pilot Study

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of fertile age. Some studies suggest that a ketogenic diet (KD) may have a role in treating PCOS. We aimed to demonstrate the long-term effectiveness of a KD in PCOS. Methods: Eighteen patients with PCOS phenotype A were enrolled: 28% were of normal weight, 28% were overweight, and 44% had obesity. All participants followed a KD without meal replacements for 45 days. After this period, patients underwent gradual carbohydrate reintroduction over 45 days, and thereafter healthy eating indications were given. Twelve patients completed the study. The patients were assessed at baseline and after 6 months. Anthropometric data, body composition, pelvic ultrasound, blood chemistry, hirsutism, and menstrual cycles frequency were recorded; Results: Besides improvement in anthropometric parameters, menstrual cycles (p 0.012), ovarian volume (p 0.029), FSH (p 0.05), LH (p 0.037), and progesterone (p 0.017) improved independently of weight or fat loss. However, testosterone and hirsutism improvements were influenced by weight and fat mass reduction. Conclusions: Our study showed that a KD followed by gradual carbohydrate reintroduction in PCOS has beneficial effects medium term, mostly independent of body weight loss, even in normal-weight women, suggesting that nutritional ketosis exerts beneficial effects per se.

Nicotinamide Mononucleotide Alleviates Bile Acid Metabolism and Hormonal Dysregulation in Letrozole-Induced PCOS Mice

Polycystic ovary syndrome (PCOS) involves complex genetic, metabolic, endocrine, and environmental factors. This study explores the effects of nicotinamide mononucleotide (NMN) in a letrozole-induced PCOS mouse model, focusing on metabolic regulation. Letrozole-induced aromatase inhibition elevated androgen and reduced bile acid levels, linking liver dysfunction and gut imbalance to PCOS. Letrozole-treated mice exhibited disrupted estrous cycles, ovarian congestion, and elevated testosterone. NMN intervention alleviated hyperandrogenism, ovarian abnormalities, and bile acid decline but did not fully restore the estrous cycle or improve lipid profiles. Metabolomic analysis showed that NMN partially reversed bile acid and lipid metabolism disturbances. These findings highlight NMN’s protective role in reducing hyperandrogenism and ovarian cyst formation. However, effective PCOS treatment should target liver and gut metabolism, not just ovarian symptoms, to mitigate systemic effects. Bile acid dysregulation may play a key role in PCOS progression and warrants further investigation.

A retrospective analysis of the Svayampurna Upacara Therapy in addressing PCOD symptoms

Introduction: This study assesses the efficacy of Svayampurna Upacara therapy, a holistic energy-based treatment, in managing Polycystic Ovarian Syndrome (PCOS). Conducted retrospectively on 150 women treated from 1995 to 2024 at Niraamay Wellness Center in Maharashtra, the study included energy healing, yoga, and meditation counselling over 12 weeks. The therapy aims to balance Panch Tattva (five elements) and align Chakras to address the root causes of PCOS symptoms. Materials and Methods: The study was conducted on 150 women with PCOS, using Svayampurna Upacara therapy. Over 12 weeks, participants underwent energy healing, Yoga, and meditation counselling, focusing on balancing Panch Tattva and Chakra alignment. Outcomes were assessed using McNemar's Chi-square test. Results: The results showed significant improvements in menstrual cycle regularity and reduced dysmenorrhea severity. Body Mass Index (BMI) management was more effective in underweight and normal BMI participants, with modest changes observed in higher BMI individuals, likely due to Pruthvi and Jal Tattva imbalances. Additionally, there were notable improvements in hirsutism, hair shedding, acne severity, and emotional parameters, as measured by the Depression, Anxiety, and Stress Scale-10. Discussion: The study highlights the potential of Svayampurna Upacara therapy in stabilizing mood swings and enhancing emotional well-being by addressing Tattva imbalances. However, the findings underscore the need for further research with larger, controlled studies to validate these results and establish the treatment's clinical efficacy. Overall, Svayampurna Upacara therapy offers a comprehensive approach to managing PCOS, addressing both physical and emotional health through energy balancing techniques.

Effect of acupuncture on primary hypothyroidism and irregular menstruation in infertile women: a randomised controlled study

IntroductionThis study aimed to examine the impact of acupuncture and a low-caloric diet on primary hypothyroidism and irregular menstruation in infertile women.MethodsSixty infertile women participated in the trial. All women were diagnosed with hypothyroidism, polycystic ovarian syndrome (PCOS), and oligomenorrhea. They were between the ages of 20 and 35, with a BMI between 30 and 34.9 kg/m2. They were divided at random into two equal groups. For four months, a control group was given thyroxine tablets once daily with a low-calorie diet (1200 kcal/day). The study group was given the same treatment and acupuncture sessions, twice a week for four months. BMI, waist, waist-to-stature ratio (WSR), free thyroxine (FT4), thyroid-stimulating hormone (TSH), luteinising hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio, menstrual cycle period, and a health-related quality-of-life questionnaire (PCOSQ) were evaluated for all patients.ResultsThere was a significant reduction in waist circumference, WSR, BMI, LH, LH/FSH ratio, TSH, and menstrual cycle period in both groups (<i>p</i> < 0.05) and a significant increase (<i>p</i> < 0.05) in FT4 and PCOSQ scores. Also, there was a significant increase in FSH in the study group. Compared to the control group, the study group revealed a significant reduction (<i>p</i> < 0.05) in waist circumference, WSR, LH, TSH, LH/FSH ratio, menstrual cycle period, and a significant increase in PCOSQ scores and FSH.ConclusionsAdding acupuncture to a low-caloric diet and medical treatment has an effective role in decreasing abdominal adiposity and improving the hormonal profile and menstrual cycle, which in turn improves reproductive health in infertile women with hypothyroidism.

Dietary Antrodia cinnamomea Polysaccharide Intervention Modulates Clinical Symptoms by Regulating Ovarian Metabolites and Restructuring the Intestinal Microbiota in Rats with Letrozole-Induced PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.

Six-month randomized, placebo controlled trial of synbiotic supplementation in women with polycystic ovary syndrome undergoing lifestyle modifications.

To determine whether long-term administration of synbiotics affects clinical, endocrine and metabolic aspects of polycystic ovary syndrome (PCOS) in overweight and obese subjects undergoing intensive lifestyle modifications. During six-month trial, all subjects underwent intensive lifestyle modifications (diet and exercise). The subjects were randomized (1:1) to receive synbiotic supplementation (Synbiotic Group) or placebo (Placebo Group). Subjects in the Placebo Group and the Synbiotic Group experienced significant reduction of BMI (-8% and -11%, respectively; both at P < 0.0001) and body fat percentage (-11% and -14%, respectively; both at P < 0.0001). These effects were statistically comparable for both groups. Total testosterone was not significantly changed in the Placebo Group (-5%, P = 0.41) while it greatly declined in the Synbiotic Group (-40%; P < 0.0001); the difference between these groups was significant (P = 0.0002). Synbiotic supplementation was superior to placebo in reducing LH (-21%; P = 0.047), total cholesterol (-6%; P = 0.002), low-density lipoprotein cholesterol (-6%; P = 0.044), triglycerides (-29%; P = 0.049), LPS (-23%; P = 0.001) and LPS-binding protein (-21%; P = 0.001). Synbiotic supplementation led to a marked improvement of several key clinical and laboratory aspects of PCOS including an improvement of hyperandrogenism, lipid profile, and markers of endotoxemia. Clinical Trial Registration Number: NCT03325023 (URL, clinicaltrials.gov; date of registration 10/26/2017).

Polycomb in female reproductive health: patterning the present and programming the future.

Epigenetic modifications regulate chromatin accessibility, gene expression, cell differentiation and tissue development. As epigenetic modifications can be inherited via mitotic and meiotic cell divisions, they enable a heritable memory of cell identity and function and can alter inherited characteristics in the next generation. Tight regulation of epigenetic information is critical for normal cell function and is often disrupted in diseases including cancer, metabolic, neurological and inherited congenital conditions. The ovary performs critical functions in female reproductive health and fertility, including oocyte and sex-hormone production. Oocytes undergo extensive epigenetic programming including the establishment of maternal genomic imprints, which are critical for offspring health and development. Epigenetic modifiers also regulate ovarian somatic cells, such as granulosa and theca cells which support oocytes and produce hormones. While ovarian dysfunction contributes to serious ovarian conditions such as primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS) and ovarian cancers, the roles of epigenetic modifications in the ovary and their contribution to ovarian dysfunction are not properly understood. Here we review recent advancements in understanding Polycomb proteins, important epigenetic modifiers that have emerging roles in ovarian development and maternal epigenetic inheritance. Polycomb group proteins (PcGs) contribute to the faithful establishment of epigenetic information in oocytes, a process essential for normal offspring development in mice. Emerging evidence also indicates that PcGs regulate ovarian function and female fertility. Understanding these and similar mechanisms will provide greater insight into the epigenetic regulation of ovarian and oocyte function, and how its disruption can impact reproductive health and maternal inheritance.

The impact of a lifestyle promotion program on anthropometric and clinical manifestations in adolescents with polycystic ovarian syndrome: a randomized controlled trial

BackgroundLifestyle modification can have beneficial effects on improving symptoms of ovary syndrome and anthropometric changes, particularly in obese individuals… However, it is not clear whether these affects in obese adolescents with PCOS are the same as non-PCOS adolescents. We had a study question” Can lifestyle promotion programs, which focus on changing behavioral habits, have an effect on anthropometric parameters and the manifestation of polycystic ovary syndrome (PCOS) in adolescents?”MethodsThis was a cluster randomized trial (CRT) that started from January 2021 and follow-up ended in March 2022. 128 participants included adolescent girls (from 14 to 18 years old). The status of PCOS was determined for the participants, following which both the PCOS-afflicted and non-PCOS cohorts were subjected to randomization to either partake in a lifestyle promotion program or to proceed without it. This program included eight sessions that were designed to be implemented for two months. This intervention provides recommendations for a balanced diet and regular exercise, as well as advice on behavior change for adolescents, including those with PCOS, regardless of their weight. All participants were followed up for 12 months and were evaluated at three time points: baseline, 6 and 12 months. Outcomes included changes in the anthropometric indices (weight, hip and waist circumstance), regularity of menstrual cycle, hirsutism score by the modified-Ferriman-Gallwey scale, acne score by the Investigator’s Global Assessment Scale, hair loss scores by the Sinclair Graphic Instrument and then physical activity by the Caspian tool and dietary intake status by the Food Frequency Questionnaire. Data was analyzed using the non-parametric Mann-Whitney test for variables with two-time point assessments and generalized estimation equations (GEE) for variables with three time point assessments.ResultsIn the study, the intervention group of girls with PCOS exhibited a significant reduction in weight and waist circumference, with an average decrease of 3.14 kg and 4.68 cm, respectively (P < 0.001), compared to the PCOS control group. Similarly, the non-PCOS intervention group showed a decrease in these factors by 2.60 kg and 4.95 cm (P < 0.001) when compared to the non-PCOS control group. After 12 months of intervention, the odds ratio (OR) for menstrual regularity in the PCOS intervention group increased to 3.30 (95% CI: 2.06, 5.25), and the acne score significantly decreased with an OR of 0.46 (95% CI: 0.31, 0.70). In contrast, the non-PCOS intervention group experienced an increase in the OR for menstrual regularity to 2.45 (95% CI: 1.33, 4.25) and an improved in acne score with an OR of 0.44 (95% CI: 0.28, 0.69). No notable differences were observed in the nutritional status among all groups post-intervention. However, a significant increase in physical activity levels, measured in metabolic equivalent minutes per week (met/min/week), was recorded in both intervention groups (p < 0.05).ConclusionManifestations of PCOS in adolescents are improved by a lifestyle promotion program and high schools are considered an appropriate setting to identify those with PCOS and the implementation of a lifestyle modification program. This program was also shown to promote healthy lifestyles for non-PCOS adolescents.Trial registrationTrial registration number: irct.ir number: IRCT20200114046123N1.

Butyrate as a Potential Modulator in Gynecological Disease Progression

This review investigates the therapeutic potential of butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, in the prevention and treatment of various gynecological diseases, including polycystic ovary syndrome (PCOS), endometriosis, and gynecologic cancers like cervical and ovarian cancer. These conditions often pose treatment challenges, with conventional therapies offering limited and temporary relief, significant side effects, and a risk of recurrence. Emerging evidence highlights butyrate’s unique biological activities, particularly its role as a histone deacetylase (HDAC) inhibitor, which allows it to modulate gene expression, immune responses, and inflammation. In PCOS, butyrate aids in restoring hormonal balance, enhancing insulin sensitivity, and reducing chronic inflammation. For endometriosis, butyrate appears to suppress immune dysregulation and minimize lesion proliferation. Additionally, in cervical and ovarian cancers, butyrate demonstrates anticancer effects through mechanisms such as cell cycle arrest, apoptosis induction, and suppression of tumor progression. Dietary interventions, particularly high-fiber and Mediterranean diets, that increase butyrate production are proposed as complementary approaches, supporting natural microbiota modulation to enhance therapeutic outcomes. However, butyrate’s short half-life limits its clinical application, spurring interest in butyrate analogs and probiotics to maintain stable levels and extend its benefits. This review consolidates current findings on butyrate’s multifaceted impact across gynecological health, highlighting the potential for microbiota-centered therapies in advancing treatment strategies and improving women’s reproductive health.

Advances in cardiometabolic outcomes in polycystic ovary syndrome.

Advances in cardiometabolic outcomes in polycystic ovary syndrome.

Psychometric properties of the Iranian version of the polycystic ovary syndrome quality of life questionnaire for married and unmarried women with PCOS: PCOSQoL-47 and PCOSQoL-42

IntroductionThe incidence of PCOS is notably elevated in Iran, making it crucial to examine the quality of life among these individuals. This study aimed to thoroughly evaluate the psychometric properties of the Iranian adaptations of the PCOSQoL-47 and PCOSQoL-42 questionnaires. The application of these tools is significant as they could enhance further research in in communities with similar social norms concerning marriage and sexuality.MethodsThis study employed a cross-sectional design. Following the linguistic validation of the Iranian adaptation of the PCOSQoL-47 and PCOSQoL-42, a panel of experts reviewed the items through an evaluation of the content validity index (CVI) and content validity ratio (CVR). Subsequently, a semi-structured interview was carried out to evaluate face validity. Consequently, discriminant validity was assessed using the known groups comparison. Convergent validity was evaluated by assessing the correlation between similar content on the PCOSQoL-47 and PCOSQoL-42, SF-12 and body image questionnaire. Responsiveness was assessed by comparing two scales scoring in baseline and eight-week follow-up data of prescription contraceptive Daine-35. In addition, reliability analyses including internal consistency and test–retest analysis were carried out.ResultsThe CVR in this study for the total scale was 0.98 for two scales, indicating a satisfactory result. The CVI for the scale was found to be 0.98 and 0.99 for PCOSQoL-42 and PCOSQoL-47, respectively suggesting that it had a good content validity. Known groups comparison revealed that the two scales effectively distinguished between sub-groups of women with varying symptoms specific to PCOS, thereby supporting their discriminant validity. Additionally, convergent validity was evaluated and, as anticipated, a strong positive correlation was observed between corresponding subscales of the two instruments. The paired t-test showed significant changes in PCOSQoL-47 and PCOSQoL-42 scores (p < 0.001) indicating as a responsive outcome measure to detect significant changes over time before and after treatment. Additional analyses indicated satisfactory results of PCOSQoL-42 for internal consistency (Cronbach’s alpha ranging from 0.72 to 0.78) and intraclass correlation coefficients (ranging 0.67 to 0.92; P < 0.05). regarding PCOSQoL-47, Cronbach’s alpha ranging from 0.80 to 0.82 and intraclass correlation coefficients (ranging 0.61 to 0.73; P < 0.05).ConclusionThe PCOSQoL-47 and PCOSQoL-42 have undergone thorough testing in Iran and may be utilized as outcome measures in forthcoming studies within this demographic.

Exploring Bioinformatics Tools to Analyze the Role of CDC6 in the Progression of Polycystic Ovary Syndrome to Endometrial Cancer by Promoting Immune Infiltration

Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration.

MicroRNAs as Biomarkers and Therapeutic Targets in Female Infertility

The study of microRNAs (miRNAs) has emerged in recent decades as a key approach to understanding the pathophysiology of many diseases, exploring their potential role as biomarkers, and testing their use as future treatments. Not only have neurological, cardiovascular diseases, or cancer benefited from this research but also infertility. Female infertility, as a disease, involves alterations at multiple levels, such as ovarian and uterine alterations. This review compiles the latest studies published in humans that link female disorders that affect fertility with altered miRNA profiles. Studies on ovarian alterations, including diminished ovarian reserve (DOR), poor ovarian response to stimulation (POR), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are summarized and classified based on the expression and type of sample analyzed. Regarding uterine disorders, this review highlights upregulated and downregulated miRNAs primarily identified as biomarkers for endometriosis, adenomyosis, decreased endometrial receptivity, and implantation failure. However, despite the large number of studies in this field, the same limitations that reduce reproducibility are often observed. Therefore, at the end of this review, the main limitations of this type of study are described, as well as specific precautions or safety measures that should be considered when handling miRNAs.

Nutritional Studies Evaluating Ketogenic Diets as a Treatment for Obesity and Obesity-Associated Morbidities: Underlying Mechanisms and Potential for Clinical Implementation

Background: The ketogenic diet (KD), characterized by high-fat content, virtually no carbohydrates, and adequate protein intake, induces a metabolic state resembling fasting, as the absence of carbohydrates forces the body to rely on the energetic supply from hepatically produced ketone bodies using free fatty acids as substrate. While the KD is clinically used in pharmacologically refractory epilepsy and specific genetic conditions such as GLUT1 deficiency, recent research suggests that, due to its “fasting mimicking” properties, the KD may also beneficially affect obesity and obesity-associated metabolic diseases. Results: Here, we present a narrative review discussing completed and ongoing nutritional studies in human volunteers specifically addressing the potential of the ketogenic diet as an anti-obesity approach and, from a larger perspective, as an intervention to ameliorate the metabolic state in conditions such as type 1 and 2 diabetes and polycystic ovary syndrome (PCOS). Published studies as well as ongoing clinical trials will be discussed. Efficacy and safety considerations will be discussed, as well as the potential physiological mechanisms mediating the effects of the KD in humans in the context of the (i) energy balance model (EBM) and (ii) carbohydrate–insulin model (CIM) of body weight control. Conclusion: Ketogenic diets may be beneficial to attenuate obesity and improve obesity-related metabolic disease, and here, we try, based on current evidence, to define the boundaries of the KD’s nutritional and clinical usefulness.

Comparative evaluation of ChatGPT-4, ChatGPT-3.5 and Google Gemini on PCOS assessment and management based on recommendations from the 2023 guideline.

Artificial intelligence (AI) is increasingly utilized in healthcare, with models like ChatGPT and Google Gemini gaining global popularity. Polycystic ovary syndrome (PCOS) is a prevalent condition that requires both lifestyle modifications and medical treatment, highlighting the critical need for effective patient education. This study compares the responses of ChatGPT-4, ChatGPT-3.5 and Gemini to PCOS-related questions using the latest guideline. Evaluating AI's integration into patient education necessitates assessing response quality, reliability, readability and effectiveness in managing PCOS. To evaluate the accuracy, quality, readability and tendency to hallucinate of ChatGPT-4, ChatGPT-3.5 and Gemini's responses to questions about PCOS, its assessment and management based on recommendations from the current international PCOS guideline. This cross-sectional study assessed ChatGPT-4, ChatGPT-3.5, and Gemini's responses to PCOS-related questions created by endocrinologists using the latest guidelines and common patient queries. Experts evaluated the responses for accuracy, quality and tendency to hallucinate using Likert scales, while readability was analyzed using standard formulas. ChatGPT-4 and ChatGPT-3.5 attained higher scores in accuracy and quality compared to Gemini (p = 0.001, p < 0.001 and p = 0.007, p < 0.001 respectively). However, Gemini obtained a higher readability score compared to the other chatbots (p < 0.001). There was a significant difference between the tendency to hallucinate scores, which were due to the lower scores in Gemini (p = 0.003). The high accuracy and quality of responses provided by ChatGPT-4 and 3.5 to questions about PCOS suggest that they could be supportive in clinical practice. Future technological advancements may facilitate the use of artificial intelligence in both educating patients with PCOS and supporting the management of the disorder.

Exploring Causal Associations Between Serum Inflammatory Markers and Female Reproductive Disorders: A Mendelian Randomisation Study

Although inflammation may disrupt immunoendocrine crosstalk essential for female reproductive function, causal links to disorders like polycystic ovary syndrome (PCOS) and endometriosis remain unestablished. This study aimed to utilise Mendelian randomisation (MR) methods to explore causal associations between serum inflammatory markers and common reproductive disorders, aiming to identify novel mechanisms and potential avenues for treatment. Total causal effects of serum inflammatory markers (interleukins, monocyte chemoattractant protein-1, etc.) on female reproductive disorders in large sample cohorts of Finnish ancestry were assessed using univariable two-sample MR methods, including the inverse variance weighted (IVW) method as the primary analysis, with relevant quality assessments (e.g., leave-one out, heterogeneity, and horizontal pleiotropy testing). The main outcome measures were PCOS (642 cases and 118,228 controls) and endometriosis (8288 cases and 68,969 controls) from the FINNGEN cohort. Monocyte chemoattractant protein-1/C-C motif chemokine ligand demonstrated a positive causal association with polycystic ovary syndrome (odds ratio [95% CI]: 1.48 [1.10, 2.00], p = 0.0097), while higher interleukin-9 levels were positively associated with endometriosis (1.15 [1.02, 1.30], p = 0.0277), both via the IVW method. These markers should be investigated as key candidates for future research into the mechanistic pathways underpinning these conditions.