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Current Medical Research and Opinion Jun 2024Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is... (Review)
Review
Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is drastically increasing in the Indo-Asian ethnicity over the recent years. According to Rotterdam criteria, PCOS is characterized by clinical or biochemical excess androgen and polycystic ovarian morphology; however, it has been established in the recent years that PCOS exacerbates to further serious metabolic conditions on the long term. This is a narrative literature review and not systematic review and is based on PubMed searches with relevant keywords "Polycystic ovarian syndrome AND acarbose OR metformin OR myoinositol; PCOS AND metabolic syndrome OR cardiovascular disease OR menstrual irregularity OR infertility OR chronic anovulation OR clinical hyperandrogenism" used in the title and are limited to articles published in English language with no time limits. A prominent aspect of PCOS is hyperandrogenaemia and hyperinsulinemia. About 50-70% of afflicted women have compensatory hyperinsulinemia and close to one tierce suffer from anovulation and infertility. Insulin resistance leads to metabolic complications and works with luteinizing hormone in increasing the ovarian androgen production. This excess androgen leads to clinical manifestations, irregular menstrual cycles and infertility. There isn't an entire cure, only the symptomatic clinical factors are considered rather than focusing on the underlying long-term complications. Therefore, the article focuses on a potent alpha glucosidase inhibitor, acarbose which suppresses the post meal glucose and insulin by delaying the absorption of complex carbs. It exhibits cardio-metabolic and hormonal benefits and is well tolerable in the south asian population. This review highlights the safety, effectiveness of acarbose in ameliorating the long-term complications of PCOS.
PubMed: 38771729
DOI: 10.1080/03007995.2024.2358237 -
The Journal of Steroid Biochemistry and... May 2024Polycystic ovary syndrome (PCOS) is the most common cause of anovulation and infertility in women. Inflammation and oxidative stress are considered to be the causes of...
Polycystic ovary syndrome (PCOS) is the most common cause of anovulation and infertility in women. Inflammation and oxidative stress are considered to be the causes of ovarian dysfunction in PCOS. Dimethyl itaconate, as a macrophage-derived immunometabolite, has anti-inflammatory and antioxidative properties, but limited data are available about its effect on female reproductive dysfunctions. The present study aimed to determine the effects of dimethyl itaconate, a cell-permeable derivative of itaconate, on the histological changes, oxidative stress, and inflammation in the ovaries of PCOS rats. In this experimental study, 48 mature female Wistar rats (160-180 g) were randomly divided into the six groups including control, PCOS, PCOS+DMI, PCOS+ metformin, control DMI and control metformin. Following PCOS induction by using testosterone enanthate (1 mg/100 g/day for 35 days), the animals were treated with DMI (50 mg/kg) or metformin (300 mg/kg) for 30 days. At the end of the experimental period, the insulin resistance markers (serum insulin and glucose concentrations, and the homeostasis model assessment of basal insulin resistance (HOMA-IR), oxidative stress index (OSI), and inflammatory cytokines were measured. The process of Folliculogenesis was evaluated by histological examination of the ovary. The results showed that DMI improved insulin resistance and decreased TNF- and IL-1β levels and OSI in the ovarian tissue of rats following androgen-induced PCOS. It also improved steroidogenesis and Folliculogenesis by reducing cystic follicles and ovarian tissue structure. Results indicated that DMI may be a potential candidate to ameliorate PCOS adverse effects by reducing insulin resistance, inflammation, and oxidative stress and restoring ovarian Folliculogenesis.
PubMed: 38754523
DOI: 10.1016/j.jsbmb.2024.106546 -
Fertility and Sterility May 2024The prevalence of obesity has doubled among reproductive-age adults in the US over the past 40 years and is projected to impact half of the population by 2030. Obesity... (Review)
Review
The prevalence of obesity has doubled among reproductive-age adults in the US over the past 40 years and is projected to impact half of the population by 2030. Obesity is associated with a twofold to threefold increase in infertility, largely because of anovulation, and is associated with a lower rate of pregnancy with ovulation induction among anovulatory women. As a result of these trends and associations, in vitro fertilization (IVF) care will need to be adapted to provide safe, effective, and equitable access for patients with obesity. Research over the past 10 years has demonstrated safe sedation practices and effective procedure modifications for oocyte retrievals and embryo transfers in patients with obesity undergoing IVF treatment. We encourage IVF medical directors to revisit body mass index restrictions for IVF treatment in favor of individualized patient risk assessments to minimize weight bias and provide timely access to safe and effective IVF care for patients with obesity and infertility.
PubMed: 38750875
DOI: 10.1016/j.fertnstert.2024.05.140 -
Biochimica Et Biophysica Acta.... Aug 2024Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading...
Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).
Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.
Topics: Female; Follicular Fluid; Insulin-Like Growth Factor I; Animals; Glutathione Peroxidase GPX1; Ovarian Cysts; Homeostasis; Selenocysteine; Oxidation-Reduction; Reactive Oxygen Species; Goats; Oxidative Stress; Glutathione Peroxidase; Oocytes; Humans; Ovarian Follicle; Proteomics
PubMed: 38744343
DOI: 10.1016/j.bbadis.2024.167235 -
Journal of Medicine and Life Jan 2024Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Polycystic ovary syndrome is the most common cause of oligo-ovulation and anovulation among women of reproductive age, contributing to infertility. This study aimed to compare the effects of green tea tablets and metformin on ovulation, menstrual cycle regularity, and antioxidant biomarkers in women with polycystic ovary syndrome (PCOS). In this clinical trial study, 94 women with PCOS were randomly assigned to three groups: green tea ( = 33), metformin ( = 29), and control ( = 32). Menstrual status and oxidative stress parameters, including total antioxidant capacity, thiol, and lipid peroxidation, were compared before and 3 months after the intervention among all three groups. Data analysis was conducted using SPSS software version 22 and employing the analysis of variance and paired t-tests. Following the intervention, the mean menstrual cycle duration in the green tea, metformin, and control groups was 32.22 ± 12.78, 48.72 ± 37.06, and 48.53 ± 31.04 days, respectively ( = 0.040). There was no statistically significant difference between the three groups in terms of biochemical, hormonal, and antioxidant indices before and after the intervention ( > 0.05). The intake of green tea tablets was associated with better outcomes in regulating the menstrual cycle in women with PCOS.
Topics: Humans; Polycystic Ovary Syndrome; Female; Metformin; Tea; Menstrual Cycle; Adult; Ovulation; Tablets; Young Adult; Antioxidants; Oxidative Stress
PubMed: 38737668
DOI: 10.25122/jml-2022-0066 -
Cytokine Jul 2024Polycystic ovarian syndrome (PCOS) is one of the most common (about 5-20%) reproductive disorders in women of reproductive age; it is characterized by polycystic...
AIMS
Polycystic ovarian syndrome (PCOS) is one of the most common (about 5-20%) reproductive disorders in women of reproductive age; it is characterized by polycystic ovaries, hyperandrogenism, and oligo/ anovulation. The levels and expression of ovarian adipokines are deregulated in the PCOS. Apelin is an adipokine that acts through its receptor (APJ) and is known to express in the various tissues including the ovary. It has also been suggested that apelin and APJ could be targeted as therapeutic adjuncts for the management of PCOS. However, no study has been conducted on the management of PCOS by targeting the apelin system. Thus, we aimed to evaluate its impact on combating PCOS-associated ovarian pathogenesis.
METHODS
The current work employed a letrozole-induced-hyperandrogenism PCOS-like mice model to investigate the effects of apelin13 and APJ, antagonist ML221. The PCOS model was induced by oral administration of letrozole (1 mg/kg) for 21 days. A total of four experimental groups were made, control, PCOS control, PCOS + aplein13, and PCOS + ML221. The treatment of apelin13 and ML221 was given from day 22 for two weeks.
KEY FINDINGS
The letrozole-induced PCOS-like features such as hyperandrogenism, cystic follicle, decreased corpus luteum, elevated levels of LH/FSH ratio, and up-regulation of ovarian AR expression were ameliorated by apelin13 and ML221 treatment. However, the PCOS-augmented oxidative stress and apoptosis were suppressed by apelin 13 treatments only. ML221 treatment still showed elevated oxidative stress and stimulated apoptosis as reflected by decreased antioxidant enzymes and increased active caspase3 and Bax expression. The expression of ERs was elevated in all groups except control. Furthermore, the PCOS model showed elevated expression of APJ and apelin13 treatment down-regulated its own receptor. Overall, observing the ovarian histology, corpus luteum formation, and decreased androgen levels by both apelin13 and ML221 showed ameliorative effects on the cystic ovary.
SIGNIFICANCE
Despite the similar morphological observation of ovarian histology, apelin13 and ML221 exhibited opposite effects on oxidative stress and apoptosis. Therefore, apelin13 (which down-regulates APJ) and ML221 (an APJ antagonist) may have suppressed APJ signalling, which would account for our findings on the mitigation of polycystic ovarian syndrome. In conclusion, both apelin13 and ML221 mediated mitigation have different mechanisms, which need further investigation.
Topics: Letrozole; Polycystic Ovary Syndrome; Animals; Female; Apelin Receptors; Mice; Apelin; Ovary; Oxidative Stress; Hyperandrogenism; Apoptosis; Disease Models, Animal
PubMed: 38733946
DOI: 10.1016/j.cyto.2024.156639 -
Acta Paediatrica (Oslo, Norway : 1992) Jul 2024
Topics: Humans; Polycystic Ovary Syndrome; Female; Adolescent; Contraceptives, Oral, Combined; Hyperandrogenism; Androgens
PubMed: 38727034
DOI: 10.1111/apa.17271 -
Journal of the Endocrine Society Apr 2024
PubMed: 38721111
DOI: 10.1210/jendso/bvae074 -
American Journal of Reproductive... May 2024Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, with...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, with hyperandrogenism being the most prominent feature of PCOS patients. However, whether excessive androgens also exist in the ovarian microenvironment of patients with PCOS, and their modulatory role on ovarian immune homeostasis and ovarian function, is not clear.
METHODS
Follicular fluid samples from patients participating in their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were collected. Androgen concentration of follicular fluid was assayed by chemiluminescence, and the macrophage M1:M2 ratio was detected by flow cytometry. In an in vitro model, we examined the regulatory effects of different concentrations of androgen on macrophage differentiation and glucose metabolism levels using qRT-PCR, Simple Western and multi-factor flow cytometry assay. In a co-culture model, we assessed the effect of a hyperandrogenic environment in the presence or absence of macrophages on the function of granulosa cells using qRT-PCR, Simple Western, EdU assay, cell cycle assay, and multi-factor flow cytometry assay.
RESULTS
The results showed that a significantly higher androgen level and M1:M2 ratio in the follicular fluid of PCOS patients with hyperandrogenism. The hyperandrogenic environment promoted the expression of pro-inflammatory and glycolysis-related molecules and inhibited the expression of anti-inflammatory and oxidative phosphorylation-related molecules in macrophages. In the presence of macrophages, a hyperandrogenic environment significantly downregulated the function of granulosa cells.
CONCLUSION
There is a hyperandrogenic microenvironment in the ovary of PCOS patients with hyperandrogenism. Hyperandrogenic microenvironment can promote the activation of ovarian macrophages to M1, which may be associated with the reprogramming of macrophage glucose metabolism. The increased secretion of pro-inflammatory cytokines by macrophages in the hyperandrogenic microenvironment would impair the normal function of granulosa cells and interfere with normal ovarian follicle growth and development.
Topics: Humans; Polycystic Ovary Syndrome; Female; Granulosa Cells; Macrophages; Hyperandrogenism; Adult; Follicular Fluid; Androgens; Cells, Cultured; Macrophage Activation; Cellular Microenvironment; Coculture Techniques; Cell Differentiation
PubMed: 38716832
DOI: 10.1111/aji.13854 -
Heliyon May 2024Polycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with...
BACKGROUND
Polycystic ovary syndrome (PCOS) is main cause of anovulatory infertility in women with gestational age. There are currently four distinct phenotypes associated with individualized endocrinology and metabolism. Growth differentiation factor 9 (GDF9) is a candidate as potential biomarker for the assessment of oocyte competence. The effect on oocyte capacity has not been evaluated and analyzed in PCOS phenotypes.
OBJECTIVE
We aimed to screen the expression levels of GDF9 in mature follicles of women with controlled ovarian hyperstimulation (COS) with different PCOS phenotypes. To determine the correlation between the expression level of GDF9 and oocyte development ability.
METHODS
In Part 1, we conducted a retrospective study comparing the clinical outcomes and endocrine characteristics of patients with PCOS according to different subgroups (depending on the presence or absence of the main features of polycystic ovarian morphology (PCOM), hyperandrogenism (HA), and oligo-anovulation (OA)) and non-PCOS control group. We stratified PCOS as phenotype A (n = 29), phenotype B (n = 18) and phenotype D (n = 24). In Part 2, the expression of GDF9 in follicular fluid (FF) and cumulus cells (CCs) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively.
RESULTS
In Part 1, the baseline clinical, hormonal, and ultrasonographic characteristics of the study population were matched with the presence or absence of the cardinal features of each PCOS phenotypes showed a clear difference. Phenotypes A and D had statistically significant associations with blastocyst formation and clinical pregnancy compared with phenotypes B ( < 0.001). In Part 2, the levels of GDF9 in FF and CCs for phenotype A and B were significantly were higher than those of phenotype D ( = 0.019, = 0.0015, respectively). Multivariate logistic regression analysis showed that GDF9 was an important independent predictor of blastocyst formation (P<0.001). The blastocyst formation rate of phenotype A was higher than that of phenotype B and D (P<0.001). Combining the results of the two parts, GDF9 appears to play a powerful role in the development of embryos into blastocysts.
CONCLUSIONS
GDF9 expression varies with different PCOS phenotypes. Phenotype A had higher GDF9 levels and blastocyst formation ability.
PubMed: 38711644
DOI: 10.1016/j.heliyon.2024.e29879