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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 -
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 -
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 -
Diagnostics (Basel, Switzerland) May 2024This study assesses the efficacy of ChatGPT-4, an advanced artificial intelligence (AI) language model, in delivering precise and comprehensive answers to inquiries...
This study assesses the efficacy of ChatGPT-4, an advanced artificial intelligence (AI) language model, in delivering precise and comprehensive answers to inquiries regarding managing polycystic ovary syndrome (PCOS)-related infertility. The research team, comprising experienced gynecologists, formulated 460 structured queries encompassing a wide range of common and intricate PCOS scenarios. The queries were: true/false (170), open-ended (165), and multiple-choice (125) and further classified as 'easy', 'moderate', and 'hard'. For true/false questions, ChatGPT-4 achieved a flawless accuracy rate of 100% initially and upon reassessment after 30 days. In the open-ended category, there was a noteworthy enhancement in accuracy, with scores increasing from 5.53 ± 0.89 initially to 5.88 ± 0.43 at the 30-day mark ( < 0.001). Completeness scores for open-ended queries also experienced a significant improvement, rising from 2.35 ± 0.58 to 2.92 ± 0.29 ( < 0.001). In the multiple-choice category, although the accuracy score exhibited a minor decline from 5.96 ± 0.44 to 5.92 ± 0.63 after 30 days ( > 0.05). Completeness scores for multiple-choice questions remained consistent, with initial and 30-day means of 2.98 ± 0.18 and 2.97 ± 0.25, respectively ( > 0.05). ChatGPT-4 demonstrated exceptional performance in true/false queries and significantly improved handling of open-ended questions during the 30 days. These findings emphasize the potential of AI, particularly ChatGPT-4, in enhancing decision-making support for healthcare professionals managing PCOS-related infertility.
PubMed: 38893609
DOI: 10.3390/diagnostics14111082 -
Healthcare (Basel, Switzerland) May 2024(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called...
Usefulness of the Sympto-Thermal Method with Standardized Cervical Mucus Assessment (InVivo Method) for Evaluating the Monthly Cycle in Women with Polycystic Ovary Syndrome (PCOS).
(1) Background: FABMs (fertility awareness-based methods) are methods that rely on the observation of clinical signs related to fertility found in women, the so-called fertility bioindicators. They can be a valuable tool for diagnosing monthly cycle disorders and infertility, for example, among patients with PCOS (polycystic ovary syndrome). Until now, it has been difficult for women with PCOS to use FABM, due to the difficulty of describing fertility bioindicators and their disorders due to the biology of the syndrome. The new InVivo sympto-thermal method with standardized cervical mucus assessment may provide a valuable diagnostic and therapeutic tool for observing the monthly cycle in this group of women. (2) Methods: The monthly cycle was evaluated in a group of 32 women of reproductive age. A total of 108 monthly cycle observation cards were analyzed: 35 monthly cycle cards were collected from 18 women with PCOS, and 73 monthly cycle cards collected from 14 healthy women. In addition, 32 pairs of macroscopic and microscopic images were evaluated: 17 pairs from the study group (four subjects) and 15 pairs from women in the control group (six subjects). (3) Results: We showed that in the group of patients with PCOS, menstruation was longer ( = 0.000814), the number of mucus peaks was statistically higher ( = 0.040747), and the interquartile range (IQR) of the duration of the follicular phase (calculated according to the BBT) was significantly higher (8 days) compared to women in the control group. We also observed that among all the women studied, the microscopic image of cervical mucus correlated with the cycle phase described in the observation card, as determined by reference to the BBT chart, provided that it showed the correct features. (4) Conclusions: Systematic maintenance of monthly cycle observation charts using the InVivo method can be an important supplement to the medical history, as it allows for a thorough assessment of, among others, the timing of monthly bleeding, cervical mucus symptoms, BBT changes, and the duration of the follicular and luteal phases among both healthy and PCOS women.
PubMed: 38891183
DOI: 10.3390/healthcare12111108 -
Frontiers in Cell and Developmental... 2024Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive...
Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). We performed this cohort study on patients receiving fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. All of these results reveal EDCs may disrupt female reproduction.
PubMed: 38887521
DOI: 10.3389/fcell.2024.1335028 -
Biomarker Insights 2024Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors.
OBJECTIVES
This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (; rs662799) and perilipin 1 (; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics.
DESIGN AND METHODS
This was a case-control study conducted on women with ( = 104) and without ( = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays.
RESULTS
Significant and direct associations were detected between PCOS susceptibility and SNP rs662799 and SNP rs894160 ( < .001). For SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, < .001) and hypertriglyceridaemia (OR = 17.0, = .5) than women with the G allele. For SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, < .001). For SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, = .02) and an irregular period (OR = 0.07, = .040) than women with the AT genotype.
CONCLUSION
We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.
PubMed: 38887365
DOI: 10.1177/11772719241258585 -
Research Square Jun 2024In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported...
In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART. This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1,054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated the associations between leukocyte TL and fecundability, infertility, and the use of ART. We also repeated the analyses using instrumental variables for TL, including genetic risk scores for TL and genetically predicted TL. Approximately 11% of couples had experienced infertility and 4% had used ART. TL was not associated with fecundability among women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility among women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing TL among men (OR, 1.22; CI, 1.03-1.46), but not among women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables. Our results indicate that TL is a poor biomarker of fecundability, infertility and use of ART in MoBa. Additional studies are required to replicate the association observed between TL and ART in men.
PubMed: 38883734
DOI: 10.21203/rs.3.rs-4430021/v1