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Trials Jun 2024Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the...
BACKGROUND
Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.
METHODS/DESIGN
We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.
DISCUSSION
The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.
Topics: Humans; Polycystic Ovary Syndrome; Female; Letrozole; Pregnancy; Embryo Transfer; Ovulation Induction; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Pregnancy Rate; Cryopreservation; Treatment Outcome; Fertility Agents, Female; Ovulation; China; Adult; Infertility, Female
PubMed: 38845035
DOI: 10.1186/s13063-024-08164-z -
Frontiers in Endocrinology 2024Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to...
OBJECTIVE
Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level.
METHODS
A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (<5×10) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results.
RESULTS
The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes.
CONCLUSION
Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Mendelian Randomization Analysis; Homocysteine; Polymorphism, Single Nucleotide; Vitamin B Complex; Folic Acid; Vitamin B 12; Genome-Wide Association Study; Vitamin B 6; Adult
PubMed: 38841299
DOI: 10.3389/fendo.2024.1393847 -
Journal of Ovarian Research Jun 2024Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues....
Enhancing angiogenesis and inhibiting apoptosis: evaluating the therapeutic efficacy of bone marrow mesenchymal stem cell-derived exosomes in a DHEA-induced PCOS mouse model.
BACKGROUND
Polycystic Ovary Syndrome (PCOS) is a widespread endocrine disorder among women, characterized by symptoms like ovarian cysts, hormonal imbalance, and metabolic issues. This research evaluates the therapeutic potential of Bone Marrow Mesenchymal Stem Cell-derived exosomes (BMSC-Exo) in treating PCOS symptoms within a mouse model.
METHODS
BMSC-Exo were isolated from NMRI mice, characterized using Transmission Electron Microscopy (TEM) and Nanoparticle Tracking Analysis (NTA), and administered to a PCOS mouse model induced by dehydroepiandrosterone (DHEA). The efficacy of BMSC-Exo was assessed in three groups of mice: a control group, a PCOS group, and a PCOS group treated with intravenous BMSC-Exo. Morphological changes in ovarian tissue were examined by Hematoxylin and Eosin (H&E) staining, apoptosis was determined using the TUNEL assay, and CD31 expression was analyzed through immunofluorescent staining to assess angiogenic activity.
RESULTS
The existence of BMSCs-Exo was confirmed via TEM and NTA, revealing their distinct cup-shaped morphology and a size range of 30 to 150 nanometers. H&E staining revealed that BMSCs-Exo treatment improved ovarian morphology in PCOS models, increasing corpora lutea and revitalizing granulosa cell layers, suggesting a reversal of PCOS-induced damage. TUNEL assays showed that BMSCs-Exo treatment significantly reduced apoptosis in PCOS-affected ovarian cells to levels comparable with the control group, highlighting its role in mitigating PCOS-induced cellular apoptosis. Immunofluorescence for CD31 indicated that BMSCs-Exo treatment normalized endothelial marker expression and angiogenic activity in PCOS models, suggesting its effectiveness in modulating the vascular irregularities of PCOS. Collectively, these findings demonstrate the therapeutic potential of BMSCs-Exo in addressing ovarian dysfunction, cellular apoptosis, and aberrant angiogenesis associated with PCOS.
CONCLUSION
The study substantiates the role of BMSC-Exo in mitigating the deleterious effects of PCOS on ovarian tissue, with implications for enhanced follicular development and reduced cellular stress. The modulation of CD31 by BMSC-Exo further highlights their potential in normalizing PCOS-induced vascular anomalies. These findings propel the need for clinical investigations to explore BMSC-Exo as a promising therapeutic avenue for PCOS management.
Topics: Animals; Female; Polycystic Ovary Syndrome; Exosomes; Apoptosis; Dehydroepiandrosterone; Mice; Disease Models, Animal; Mesenchymal Stem Cells; Neovascularization, Physiologic; Ovary; Angiogenesis
PubMed: 38840218
DOI: 10.1186/s13048-024-01445-w -
Gynecological Endocrinology : the... Dec 2024Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains...
OBJECTIVES
Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains elusive. This study aims to elucidate the association between these conditions and determine the potential impact of SCH on the physiological and metabolic characteristics of patients with PCOS.
METHODS
This cross-sectional study enrolled 133 patients with PCOS from our Hospital. Participants were categorized into two groups: those with PCOS + SCH ( = 58) and those with PCOS ( = 75). Serum hormonal levels, metabolic markers, ovarian volume, and follicle count were compared between the groups.
RESULTS
There was a significant difference in BMI between the two groups, with a higher prevalence of obesity in the PCOS + SCH group ( = .014). Compared to the PCOS group, patients with PCOS + SCH had significantly higher levels of TSH ( < .001), triglycerides ( = .025), and HOMA-IR ( < .001), while LH levels were significantly lower ( = .048). However, multivariate linear regression analysis revealed that TSH, triglycerides, LH, and HOMA-IR were not determinants for the occurrence of SCH in patients with PCOS. Additionally, there was a notable reduction in follicle count in the left ovary for the PCOS + SCH group compared to the PCOS group ( = .003), and the overall follicle diameter of the PCOS + SCH group was also smaller ( = .010).
CONCLUSION
SCH may exert effects on the physiological and metabolic profiles of patients with PCOS. Further investigation into the relationship between these disorders is warranted to delineate their clinical implications.
Topics: Humans; Polycystic Ovary Syndrome; Female; Hypothyroidism; Cross-Sectional Studies; Adult; Ovary; Young Adult; Thyrotropin; Insulin Resistance; Luteinizing Hormone; Body Mass Index; Triglycerides; Ovarian Follicle
PubMed: 38835150
DOI: 10.1080/09513590.2024.2358219 -
PeerJ 2024To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer...
Effect of GnRH agonist down-regulation combined with hormone replacement treatment on reproductive outcomes of frozen blastocyst transfer cycles in women of different ages.
OBJECTIVE
To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages.
METHODS
This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (<35 years old) and group B (≥35 years old), and each group was further divided into HRT and GnRHa-HRT groups. The clinical outcomes were compared between groups.
RESULTS
There was no statistically significant difference in clinical outcomes between the HRT and GnRHa-HRT groups among women aged <35 years. In women of advanced age, higher rates of clinical pregnancy and live birth were seen in the GnRHa-HRT group. Logistic regression analysis showed that female age and number of embryos transferred influenced the live birth rate in FET cycles, and in women aged ≥ 35 years, the use of GnRH-a down-regulation prior to HRT improved pregnancy outcomes.
CONCLUSIONS
In elderly woman without adenomyosis, endometriosis, PCOS, severe uterine adhesions, and RIF, hormone replacement treatment with GnRH agonist for pituitary suppression can improve the live birth rate of FET cycles.
Topics: Humans; Female; Embryo Transfer; Retrospective Studies; Adult; Gonadotropin-Releasing Hormone; Pregnancy; Down-Regulation; Hormone Replacement Therapy; Age Factors; Pregnancy Outcome; Pregnancy Rate; Embryo Implantation
PubMed: 38832029
DOI: 10.7717/peerj.17447 -
Gynecological Endocrinology : the... Dec 2024
Statement of Retraction: Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial.
PubMed: 38828774
DOI: 10.1080/09513590.2024.2349424 -
Frontiers in Endocrinology 2024Reproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with...
BACKGROUND
Reproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with high metabolic activity as it produces adipokines such as leptin and adiponectin. Our aim is to examine potential associations between women of reproductive age's ovarian reserves and their levels of leptin and adiponectin.
METHOD
74 women between 19 and 40 years of age consented to take part. Based on the patterns of their ovarian reserves, the women were divided into three main groups: women with adequate ovarian reserves (AOR - Group A, n=30), women with polycystic ovary syndrome (PCOS - Group B, n=31) and women with depleted ovarian reserves (DOR - Group C, n=13). Among these groups, several biochemical and demographic parameters were statistically compared.
RESULTS
Compared to the other two groups, women with DOR had statistically higher age and follicle stimulation hormone (FSH) levels. For estradiol (E2) and thyroid-stimulating hormone (TSH), no statistically significant difference was seen between the groups. In addition, women with PCOS had higher body mass index (BMI), luteinizing hormone (LH), total testosterone (TT), 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), anti-Mullerian hormone (AMH), and antral follicle count (AFC) than the other two groups. In line with expectations, women with DOR also had lower levels of AMH and AFC than the other two groups. Women with PCOS had higher leptin levels than the other two groups, but there was no statistically significant difference. Women with PCOS had lower levels of adiponectin than the other groups, however the difference was not statistically significant.
CONCLUSION
The way we classified women in our study according to their ovarian reserves is completely consistent with what has been published internationally. The ovarian reserve in women of reproductive age is not strongly correlated with leptin and adiponectin levels. For safe conclusions, more research including a greater number of samples is required.
Topics: Humans; Female; Leptin; Adiponectin; Ovarian Reserve; Adult; Young Adult; Polycystic Ovary Syndrome; Body Mass Index; Reproduction; Ovary
PubMed: 38828407
DOI: 10.3389/fendo.2024.1369248 -
Journal of Pathology Informatics Dec 2024Endometrial CD138+ plasma cells serve as a diagnostic biomarker for endometrial inflammation, and their elevated occurrence correlates positively with adverse pregnancy...
AI-algorithm training and validation for identification of endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF).
BACKGROUND
Endometrial CD138+ plasma cells serve as a diagnostic biomarker for endometrial inflammation, and their elevated occurrence correlates positively with adverse pregnancy outcomes. Infertility-related conditions like polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) are closely associated with systemic and local chronic inflammatory status, wherein endometrial CD138+ plasma cell accumulation could also contribute to endometrial pathology. Current methods for quantifying CD138+ cells typically involve laborious and time-consuming microscopic assessments of only a few random areas from a slide. These methods have limitations in accurately representing the entire slide and are susceptible to significant biases arising from intra- and interobserver variations. Implementing artificial intelligence (AI) for CD138+ cell identification could enhance the accuracy, reproducibility, and reliability of analysis.
METHODS
Here, an AI algorithm was developed to identify CD138+ plasma cells within endometrial tissue. The AI model comprised two layers of convolutional neural networks (CNNs). CNN1 was trained to segment epithelium and stroma across 28,363 mm (2.56 mm of epithelium and 24.87 mm of stroma), while CNN2 was trained to distinguish stromal cells based on CD138 staining, encompassing 7345 cells in the object layers (6942 CD138- cells and 403 CD138+ cells). The training and performance of the AI model were validated by three experienced pathologists. We collected 193 endometrial tissues from healthy controls ( = 73), women with PCOS ( = 91), and RIF patients ( = 29) and compared the CD138+ cell percentages based on cycle phases, ovulation status, and endometrial receptivity utilizing the AI model.
RESULTS
The AI algorithm consistently and reliably distinguished CD138- and CD138+ cells, with total error rates of 6.32% and 3.23%, respectively. During the training validation, there was a complete agreement between the decisions made by the pathologists and the AI algorithm, while the performance validation demonstrated excellent accuracy between the AI and human evaluation methods (intraclass correlation; 0.76, 95% confidence intervals; 0.36-0.93, = 0.002) and a positive correlation (Spearman's rank correlation coefficient: 0.79, < 0.01). In the AI analysis, the AI model revealed higher CD138+ cell percentages in the proliferative phase (PE) endometrium compared to the secretory phase or anovulatory PCOS endometrium, irrespective of PCOS diagnosis. Interestingly, CD138+ percentages differed according to PCOS phenotype in the PE ( = 0.03). On the other hand, the receptivity status had no impact on the cell percentages in RIF samples.
CONCLUSION
Our findings emphasize the potential and accuracy of the AI algorithm in detecting endometrial CD138+ plasma cells, offering distinct advantages over manual inspection, such as rapid analysis of whole slide images, reduction of intra- and interobserver variations, sparing the valuable time of trained specialists, and consistent productivity. This supports the application of AI technology to help clinical decision-making, for example, in understanding endometrial cycle phase-related dynamics, as well as different reproductive disorders.
PubMed: 38827567
DOI: 10.1016/j.jpi.2024.100380 -
Cureus May 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood.
AIM
This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS.
METHODS
The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA).
RESULTS
The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels.
CONCLUSION
The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target.
PubMed: 38826895
DOI: 10.7759/cureus.59430 -
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0270102.].
Correction: Prevalence and associated risk factors for mental health problems among patients with polycystic ovary syndrome in Bangladesh: A nationwide cross-sectional study.
[This corrects the article DOI: 10.1371/journal.pone.0270102.].
PubMed: 38820325
DOI: 10.1371/journal.pone.0304879