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Frontiers in Endocrinology 2024Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS...
High coverage of targeted lipidomics revealed lipid changes in the follicular fluid of patients with insulin-resistant polycystic ovary syndrome and a positive correlation between plasmalogens and oocyte quality.
BACKGROUND
Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown.
METHODS
A total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified.
RESULTS
The number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10 mol/L and 10 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality.
CONCLUSIONS
This study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte maturation (IVM).
Topics: Humans; Female; Polycystic Ovary Syndrome; Follicular Fluid; Oocytes; Adult; Lipidomics; Insulin Resistance; Plasmalogens; Fertilization in Vitro; Lipids; Infertility, Female; Lipid Metabolism; Embryo Transfer; Case-Control Studies
PubMed: 38904043
DOI: 10.3389/fendo.2024.1414289 -
SAGE Open Medicine 2024The purpose of this scoping review is to explore research studies on the association between chronic pain and polycystic ovary syndrome to create local (U.S.-based) and... (Review)
Review
OBJECTIVES
The purpose of this scoping review is to explore research studies on the association between chronic pain and polycystic ovary syndrome to create local (U.S.-based) and global recommendations to improve access to and quality of affordable symptom management and treatment options for patients with polycystic ovary syndrome.
METHODS
The study sections used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews as a checklist reference. The review followed the York methodology by Arksey and O'Malley for the extraction, analysis, and presentation of results in scoping reviews.
RESULTS
Final analysis included two conference abstracts published in peer-reviewed journals and two peer-reviewed articles. The relationship between pain perception and health-related quality of life warrants further investigation in patients with polycystic ovary syndrome as the interconnected pathophysiology of symptoms renders exploring associations between the two factors difficult. A comprehensive understanding of the causes of polycystic ovary syndrome-associated symptoms, particularly those relating to pain perceptions can provide more insight into polycystic ovary syndrome pathophysiology and aid in the development of innovative therapeutic approaches for long-term polycystic ovary syndrome management and care.
CONCLUSION
Future studies are necessary to examine associations between the disease and pathophysiological symptoms for a better quality of life for patients with polycystic ovary syndrome.
PubMed: 38903491
DOI: 10.1177/20503121241262158 -
BMC Women's Health Jun 2024Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary...
BACKGROUND
Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS.
METHODS
We employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association.
RESULTS
We utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39-0.78, P = 8.30 × 10) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings.
CONCLUSIONS
Through a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.
Topics: Humans; Sex Hormone-Binding Globulin; Polycystic Ovary Syndrome; Female; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Genome-Wide Association Study; Genetic Predisposition to Disease; Risk Factors
PubMed: 38902677
DOI: 10.1186/s12905-024-03144-6 -
BMJ Open Diabetes Research & Care Jun 2024We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2... (Randomized Controlled Trial)
Randomized Controlled Trial
Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics.
INTRODUCTION
We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines.
RESEARCH DESIGN AND METHODS
In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications.
RESULTS
In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m, HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes.
CONCLUSIONS
Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events.
TRIAL REGISTRATION NUMBER
NCT04049149.
Topics: Humans; Female; Male; Diabetes Mellitus, Type 2; Adult; Precision Medicine; Insulin Secretion; Middle Aged; China; Age of Onset; Young Adult; Insulin; Hypoglycemic Agents; Follow-Up Studies; Blood Glucose; Glycated Hemoglobin; Asian People; Biomarkers; Prognosis; East Asian People
PubMed: 38901858
DOI: 10.1136/bmjdrc-2024-004120 -
Current Stem Cell Research & Therapy Jun 2024In vitro maturation has been considered an approach to mature oocytes derived from women with polycystic ovary syndrome (PCOS). It is suggested that the IVM of oocytes...
BACKGROUND
In vitro maturation has been considered an approach to mature oocytes derived from women with polycystic ovary syndrome (PCOS). It is suggested that the IVM of oocytes may benefit from mesenchymal stem cells derived conditioned medium (CM-MSC).
OBJECTIVE
The purpose of this study was to determine the efficacy of a cocktail of menstrual blood stem cell (MenSCs)-derived secretome, along with follicular fluid and melatonin, in oocyte maturation and embryo development in PCOS.
METHODS
Four hundred left germinal vesicle oocytes were collected from 100 PCOS patients and randomly divided into four treatment groups: 1) control, 2) secretome, 3) follicular fluid, and 4) melatonin. Oocyte maturation, fertilization rate, and embryo development were monitored, as well as the expression levels of oocyte-secreted factors (GDF9- BMP15), oocyte maturation (MPK3), and apoptosis (BAX- Bcl2).
RESULTS
The rate of oocyte maturation increased in all test groups, but only the results for the SEC group were significant (P= 0.032). There were no significant differences in oocyte fertilization and embryo yield among groups. However, the quality of embryos significantly increased in the melatonin group compared to the control. Cytoplasmic maturation was confirmed by the expression of oocyte maturation-related genes using Real-time PCR. Additionally, the expression level of BCL-2 was significantly higher in the SEC-FF-MEL group than in the control group (p ≤ 0.01).
CONCLUSION
Enrichment of IVM media using MenSCs-secretome, particularly along with melatonin, could be an effective strategy to improve oocyte maturation and embryo development in PCOS.
PubMed: 38899597
DOI: 10.2174/011574888X298902240523103352 -
Reproductive Medicine and Biology 2024In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients...
In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients of about 2% was found. It is necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long-term effects in women with undiagnosed FHA.
PubMed: 38898999
DOI: 10.1002/rmb2.12591 -
Obstetrical & Gynecological Survey Jun 2024Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of... (Review)
Review
IMPORTANCE
Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of menstrual disorders in women of childbearing age. It has been found that branched-chain amino acids (BCAAs), a class of essential amino acids that cannot be synthesized by the human body, play a significant role in the metabolic changes of PCOS, which may be involved in the pathogenesis of PCOS.
OBJECTIVE
The purpose of this review is to summarize the relevance between BCAAs and metabolic abnormalities in PCOS and to explore their possible mechanisms.
EVIDENCE ACQUISITION
The evidence is mainly obtained by reviewing the literature on PubMed related to PCOS, BCAAs, and related metabolic abnormalities and conducting summary analysis.
RESULTS
The metabolism of BCAAs can affect the homeostasis of glucose metabolism, possibly by disrupting the balance of gut microbiota, activating mTORC1 targets, producing mitochondrial toxic metabolites, and increasing the expression of proinflammatory genes. The correlation between obesity and BCAAs in PCOS patients may be related to the gene expression of BCAA metabolism-related enzymes in adipose tissue. The association between BCAA metabolic changes and nonalcoholic fatty liver disease in PCOS patients has not been fully clarified, which may be related to the lipid accumulation caused by BCAAs. At present, it is believed that hyperandrogenism in patients with PCOS is not related to BCAAs. However, through the study of changes in BCAA metabolism in prostate cancer caused by hyperandrogenism, we speculate that the relationship between BCAAs and hyperandrogenism may be mediated by mTORC1 and amino acid transporters.
CONCLUSIONS AND RELEVANCE
Review of prior articles reveals that BCAAs may be related to insulin resistance, obesity, nonalcoholic fatty liver, and hyperandrogenism in PCOS patients, and its mechanisms are complex, diverse, and interrelated. This review also discussed the mechanism of BCAAs and these metabolic disorders in non-PCOS patients, which may provide some help for future research.
Topics: Humans; Polycystic Ovary Syndrome; Amino Acids, Branched-Chain; Female; Hyperandrogenism; Non-alcoholic Fatty Liver Disease; Obesity; Insulin Resistance
PubMed: 38896430
DOI: 10.1097/OGX.0000000000001272 -
Journal of the Endocrine Society May 2024Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive.
CONTEXT
Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive.
OBJECTIVE
We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis.
METHODS
Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed using MRI fat fraction and VCTE-based controlled attenuation parameter (CAP). Hepatosteatosis was defined as MRI fat fraction ≥5.0%. The area under the receiver-operating characteristic curves (AUROCs) for CAP against MRI was calculated, and optimal CAP using the Youden index for hepatosteatosis diagnosis was determined.
RESULTS
Data from 82 adolescents (age 15.6 ± 1.4 years, body mass index 36.5 ± 5.9 kg/m, 81% female) were included. Fifty youth had hepatosteatosis by MRI (fat fraction 9.3% ; 95% CI 6.7, 14.0), and 32 participants did not have hepatosteatosis (fat fraction 3.1%; 95% CI 2.2, 3.9; < .001). The hepatosteatosis group had higher mean CAP compared with no hepatosteatosis (293 dB/m; 95% CI 267, 325 vs 267 dB/m; 95% CI 248, 282; = .0120). A CAP of 281 dB/m had the highest sensitivity (60%) and specificity (74%) with AUROC of 0.649 (95% CI 0.51-0.79; = .04) in the entire cohort. In a subset of participants with polycystic ovary syndrome (PCOS), a CAP of 306 dB/m had the highest sensitivity (78%) and specificity (52%) and AUROC of 0.678 (95% CI 0.45-0.90; = .108).
CONCLUSION
CAP of 281 dB/m has modest diagnostic performance for hepatosteatosis compared with MRI in youth with significant obesity. A higher CAP in youth with PCOS suggests that comorbidities might affect optimal CAP in hepatosteatosis diagnosis.
PubMed: 38895640
DOI: 10.1210/jendso/bvae110 -
Frontiers in Endocrinology 2024Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use... (Review)
Review Meta-Analysis
BACKGROUND
Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception.
METHODS
Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals.
RESULTS
Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants].
CONCLUSION
Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.
Topics: Humans; Acupuncture Therapy; Female; Bibliometrics; Infertility, Female; Male; Infertility; Pregnancy; Infertility, Male
PubMed: 38894745
DOI: 10.3389/fendo.2024.1351281 -
Reproduction, Fertility, and Development Jun 2024Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFβ) during foetal development have been implicated in the...
Expression of transforming growth factor β signalling molecules and their correlations with genes in loci linked to polycystic ovary syndrome in human foetal and adult tissues.
Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFβ) during foetal development have been implicated in the predisposition to polycystic ovary syndrome (PCOS) in later life, aside from its genetic predisposition. In foetal ovarian fibroblasts, TGFβ1 has been shown to regulate androgen signalling and seven genes located in loci associated with PCOS. Since PCOS exhibits a myriad of symptoms, it likely involves many different organs. Aims To identify the relationships between TGFβ signalling molecules and PCOS candidate genes in different tissues associated with PCOS. Methods Using RNA sequencing data, we examined the expression patterns of TGFβ signalling molecules in the human ovary, testis, heart, liver, kidney, brain tissue, and cerebellum from 4 to 20weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFβ signalling molecules and PCOS candidate genes. Key results TGFβ signalling molecules were dynamically expressed in most tissues prenatally and/or postnatally. FBN3 , a PCOS candidate gene involved in TGFβ signalling, was expressed during foetal development in all tissues. The PCOS candidate genes HMGA2, YAP1 , and RAD50 correlated significantly (P TGFBR1 in six out of the seven tissues examined. Conclusions This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFβ signalling molecules in multiple tissues, particularly during foetal development. Implications Thus, alteration in TGFβ signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.
Topics: Humans; Female; Polycystic Ovary Syndrome; Signal Transduction; Transforming Growth Factor beta; Adult; Ovary; Fetus; Male; Pregnancy; Gene Expression Regulation, Developmental; Testis; Fibrillins
PubMed: 38894494
DOI: 10.1071/RD23174