Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome

Objective: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. Methods: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. Results: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. Conclusions: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS; this possibility should be confirmed in further research.

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Association between Luteinizing Hormone/Choriogonadotropin Receptor Ins18LQ Gene Polymorphism and Polycystic Ovary Syndrome

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4182 ◽

2020 ◽

Vol 8 (A) ◽

pp. 517-520

Author(s):

Hilma Putri Lubis ◽

Muhammad Fidel Ganis Siregar ◽

Ichwanul Adenin ◽

Binarwan Halim ◽

Henry Salim Siregar ◽

...

Keyword(s):

Luteinizing Hormone ◽

Polycystic Ovary Syndrome ◽

Gene Polymorphism ◽

Polycystic Ovary ◽

Control Group ◽

Control Groups ◽

Ovary Syndrome ◽

Significant Difference ◽

Pcos Group ◽

And Control

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of women in the childbearing period. However, its pathophysiology is still unclear. Certain polymorphisms of the luteinizing hormone/choriogonadotropin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. The important functional role of LHCGR in the metabolism of androgen and ovulation, the LHCGR gene variant, may be related to the risk of PCOS. AIM: The aim of this study was to evaluate the association between LHCGR Ins18LQ gene polymorphism and PCOS. METHODS: A case–control study was performed in women with PCOS and non-PCOS from May 2019 to October 2019 in HFC IVF Center. We included 50 women with PCOS and 50 healthy controls. Polymorphism of the LHCGR (ins18LQ) gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: From this study, we found that there was no significant difference in the proportion of ages between the groups (p > 0.05). There were significant differences in the characteristics of body mass index, FSH level, LH level, and LH/FSH ratio between the PCOS and control groups (p < 0.05). We also found that the proportion of heterozygote variant non-ins/ins was higher in the PCOS group compared to the control group, but there was no significant difference between the polymorphisms of the non-ins and non-nonins variants between the PCOS and control groups (p = 0.269). The frequency of ins alleles was higher in the PCOS group compared to the control group. CONCLUSION: There was no significant association between LHCGR ins18LQ gene polymorphism and PCOS.

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The Role of GnRH Receptor Autoantibodies in Polycystic Ovary Syndrome

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa078 ◽

2020 ◽

Vol 4 (8) ◽

Cited By ~ 1

Author(s):

David C Kem ◽

Hongliang Li ◽

Xichun Yu ◽

Elizabeth Weedin ◽

Anna C Reynolds ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Activity Level ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Similar Data ◽

Ovary Syndrome ◽

Therapeutic Implications ◽

Natural Ligand ◽

Activating Autoantibodies

Abstract Objective Is polycystic ovary syndrome (PCOS) associated with activating autoantibodies (AAb) to the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR)? Design and Methods We retrospectively screened sera from 40 patients with PCOS and 14 normal controls (NCs) with regular menses using enzyme-linked immunosorbent assay (ELISA) for the presence of GnRHR-ECL2-AAb. We obtained similar data from 40 non-PCOS ovulatory but infertile patients as a control group (OIC) of interest. We analyzed GnRHR-ECL2-AAb activity in purified immunoglobulin (Ig)G using a cell-based GnRHR bioassay. Results The mean ELISA value in the PCOS group was markedly higher than the NC (P = .000036) and the OIC (P = .0028) groups. IgG from a sample of 5 PCOS subjects, in contrast to a sample of 5 OIC subjects, demonstrated a dose-dependent increase in GnRHR-stimulating activity qualitatively similar to the acute action of the natural ligand GnRH and the synthetic agonist leuprolide. The GnRHR antagonist cetrorelix significantly suppressed (P < .01) the elevated GnRHR activity induced by IgG from 7 PCOS patients while the IgG activity level from 7 OIC subjects was unchanged. Five other OIC subjects had relatively high ELISA values at or above the 95% confidence limits. On further study, 3 had normal or low activity while 2 had elevated IgG-induced GnRHR activity. One suppressed with cetrorelix while the other did not. The copresence of PCOS IgG increased the responsiveness to GnRH and shifted the dosage response curve to the left (P < .01). Conclusions GnRHR-ECL2-AAb are significantly elevated in patients with PCOS compared with NCs. Their presence raises important etiological, diagnostic, and therapeutic implications.

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Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study

Journal of Ovarian Research ◽

10.1186/s13048-021-00885-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yanna Ban ◽

Haiying Ran ◽

Ying Chen ◽

Li Ma

Keyword(s):

Pilot Study ◽

Polycystic Ovary Syndrome ◽

Follicular Fluid ◽

Lipid Analysis ◽

Polycystic Ovary ◽

Normal Weight ◽

Control Group ◽

Potential Candidate ◽

Ovary Syndrome ◽

Pcos Group

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this pilot study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight. Methods Follicular fluid samples were collected from patients who underwent IVF, including normal-weight women without PCOS (control group, n = 10) and normal-weight women with PCOS (PCOS group, n = 8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. Results All 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC < 0.67, p-value < 0.05 and VIP value > 1. These differential species of lipid belong to lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI). Conclusion The identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal-weight.

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Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

10.21203/rs.2.19858/v1 ◽

2020 ◽

Author(s):

You Li ◽

Guohui Xiong ◽

Jun Tan ◽

Shudi Wang ◽

Ziyu Zhang ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Signaling Pathway ◽

Granulosa Cells ◽

Hedgehog Signaling ◽

Polycystic Ovary ◽

Control Group ◽

Hedgehog Signaling Pathway ◽

Ovary Syndrome ◽

Ovarian Granulosa Cells ◽

Pcos Group

Abstract The molecular mechanism that triggers polycystic ovary syndrome is mysterious. Abnormal ovarian granulosa cells are one of the causes of PCOS. Therefore, we carried out RNA-seq in ovarian granulosa cells from patients with PCOS and normal controls and found that Hedgehog signaling pathway members Ihh and ptch2 were abnormally highly expressed in the PCOS group. Granulosa cells from 22 patients with PCOS and 21 controls with normal ovulation were collected. Subsequent qPCR tests also indicated that the expression of ptch1, gli1, and gli2 of other downstream members of Hh in the PCOS group was significantly higher than that in the control group. These results indicate that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

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Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome

Frontiers in Endocrinology ◽

10.3389/fendo.2021.604215 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mariela Edith Velazquez ◽

Andrea L. Millan ◽

Mailén Rojo ◽

Giselle Adriana Abruzzese ◽

Silvina Ema Cocucci ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Telomere Length ◽

Polycystic Ovary ◽

Major Effect ◽

Control Group ◽

Unrelated Donor ◽

Ovary Syndrome ◽

Blood Leukocytes ◽

Real Time Quantitative Pcr ◽

Pcos Group

BackgroundPolycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).AimsTo compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.Materials and methodsThe PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.ResultsWomen with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).ConclusionsWhilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.

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Adipokine levels and carbohydrate metabolism in patients diagnosed de novo with polycystic ovary syndrome

Qatar Medical Journal ◽

10.5339/qmj.2021.34 ◽

2021 ◽

Vol 2021 (2) ◽

Author(s):

Ewelina Kolan′ska-Dams ◽

Joanna Boinska ◽

Maciej W. Socha

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Carbohydrate Metabolism ◽

De Novo ◽

Polycystic Ovary ◽

Control Group ◽

Model Assessment ◽

Ovary Syndrome ◽

Positive Correlation ◽

Pcos Group

Introduction: Central obesity appears to play a major role in the pathogenesis of metabolic disorders in polycystic ovary syndrome. Insulin resistance and carbohydrate disorders are associated with dysfunctional secretion of various adipokines by the adipose tissue. Objectives: This study aimed to evaluate leptin, apelin, and visfatin against a background of carbohydrate metabolism parameters in patients diagnosed de novo with polycystic ovary syndrome (PCOS). Material and methods: The study group consisted of 40 patients with PCOS (mean age, 29 years) diagnosed in accordance with the American Society for Reproductive Medicine criteria from 2003. The control group consisted of 37 clinically healthy women (mean age, 26 years). All controls had regular menses and no clinical or biochemical signs of hyperandrogenism. Concentrations of leptin, apelin, visfatin, and insulin were measured by immunoenzymatic methods. Glucose concentrations were determined using spectrophotometry. Results: Significantly higher concentrations of leptin, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and the immunoreactive insulin (IRI)/glucose index were found in the PCOS group than in the control group. Notably, the concentration of apelin was over five times lower in the PCOS group than in the control group. In patients with PCOS, a positive correlation was found between the concentrations of insulin and leptin and concentrations of leptin and IRI/glucose. Patients of the PCOS group with body mass index (BMI) ≥ 25 had significantly higher values of leptin, insulin, HOMA-IR index, and IRI/glucose index than patients of the PCOS group with normal BMI. In the PCOS group, a positive correlation was found between BMI and leptin concentration (r = 0.7176; p < 0.0001) and carbohydrate metabolism, such as insulin (r = 0.5524; p = 0.0003), glucose (r = 0.3843; p = 0.0157), HOMA-IR (r = 0.5895; p < 0.0001), and IRI/glucose (r = 0.3872; p = 0.0163). These findings were not observed in the control group. Conclusions: (1) Increased leptin concentration observed in women diagnosed de novo with PCOS as well as positive correlations between leptin and HOMA-IR, and IRI/glucose and BMI may indicate a potential role of leptin in the reduction of tissue sensitivity to insulin. (2) Significantly lower apelin concentration in the PCOS group (>5 fold) than in the control group, associated with a concomitant increase in leptin, may also contribute to carbohydrate metabolism disorders occurring in the course of PCOS.

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TNFR1 is Upregulated and Mediates Apoptosis in Cumulus Cells of Women With Polycystic Ovarian Syndrome

10.21203/rs.3.rs-596490/v1 ◽

2021 ◽

Author(s):

Yaping Jiang ◽

Rui Jiang ◽

Peng Zhang ◽

qiong Yu ◽

Hongping Ba ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Signaling Pathway ◽

Granulosa Cells ◽

Follicular Fluid ◽

Polycystic Ovary ◽

Cumulus Cells ◽

Control Group ◽

Ovary Syndrome ◽

Tnf Α ◽

Pcos Group

Abstract Purpose To investigate the changes of human granulosa cell, TNFR1, TNFR2 and their downstream molecules in patients with polycystic ovary syndrome (PCOS) and the control group. Methods We recruited infertile women with polycystic ovary syndrome (n = 30) and compared them with infertility due to fallopian tube obstruction(n = 30, control group). The ovaries were stimulated with GnRH agonists and gonadotropins. Follicular fluid from large follicles ([14 mm]) was pooled and granulosa cells (GCs) were separated by a cellular filter. The TNF-α level of follicular fluid was measured by ELISA. TUNEL assay were used to detect the apoptosis of purified GCs. Real-time PCR and Western blotting were used to detect the expression of TNF-related signaling molecules in GCs. Results The rate of high quality embryos in the PCOS group was lower than that in the control group. There were higher percentages of apoptosis in GCs of PCOS patients than in the control group. TNF-α is upregulated in follicular fluid of PCOS patients. TNFR1 and caspase-3 mRNA level were signifificantly higher in PCOS group than in the control group. TNF-α-mediated apoptosis of PCOS granulosa cells was mainly dependent on TNFR1.The TNF-α/TNFR1 signaling pathway mediates apoptosis rather than survival in cumulus cells of PCOS patients. Conclusions TNF-α expression was upregulated in follicular fluid of PCOS patients, and TNFR1 overexpression in female granulosa cells of PCOS was associated with higher levels of apoptosis in these cells, suggesting that the TNF-α/TNFR1 signaling pathway may be a candidate for higher apoptosis in female granulosa cells of PCOS.

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The facial expression of emotions recognition in patients with polycystic ovary syndrome

Problems of Endocrinology ◽

10.14341/probl201662535 ◽

2016 ◽

Vol 62 (5) ◽

pp. 35

Author(s):

Adam Czyzyk ◽

Kinga Polak ◽

Agnieszka Podfigurna ◽

Stanislaw Kozlowski ◽

Blazej Meczekalski

Keyword(s):

Polycystic Ovary Syndrome ◽

Facial Expression ◽

Facial Expressions ◽

Polycystic Ovary ◽

Control Group ◽

Eysenck Personality Questionnaire ◽

Ovary Syndrome ◽

Pcos Group ◽

Expression Of Emotions ◽

Time Required

Background. A facial expression of emotions recognition is one of the basic psychological abilities. Sex steroids are able to strongly modulate the process of interpretation of facial expressions, as it has been shown in Turner syndrome patients.Objective. The aim of this study was the assessment of ability to interpret the facial emotions in women with polycystic ovary syndrome (PCOS).Methods. Participants completed a visual emotional task in which they were asked to recognize the emotion expressed of 80 randomly chosen facial expressions from NimStim set (Tottenham et al., 2009). With dedicated software we were able to assess the accuracy of patients facial emotion recognition (in comparison to NimStim validation set) and time required to provide the answer. Patients with psychotic personality have been excluded using Eysenck Personality Questionnaire (EPQ). All the patients underwent also hormonal tests including gonadotropins, estradiol and androgen concentrations.Patients. 80 women diagnosed with PCOS and hyperandrogenemia were included to the study. The control group consisted of 60 healthy, euovulatory women matched by age.Intervention. Each patient underwent visual emotional and EPQ tasks using specifically designed software.Main outcome measures. The accuracy rate (AR) and time required to recognize emotion (TE) of following emotions: anger, disgust, fear, happiness, sadness, surprise, calm and neutral has been measured.Results. Patients with PCOS showed significantly reduced AR for calm (0.76¬+/-0.09) and surprise (0.67+/-0.18) emotions in comparison to controls (0.81+/-0.09, 0.79+/-0.08 respectively). The TE for the anger was higher in PCOS group. Estradiol concentrations showed a statistic tendency (p=0.07) for correlation with TE for the happiness in controls. Conclusions. In this study we showed for the first time that patients affected by hyperandrogenism shows signs of disturbed recognition of facial expression of emotions.

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Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model

Medical Principles and Practice ◽

10.1159/000494300 ◽

2018 ◽

Vol 27 (6) ◽

pp. 515-522 ◽

Cited By ~ 7

Author(s):

Atilla Karateke ◽

Recep Dokuyucu ◽

Hatice Dogan ◽

Tumay Ozgur ◽

Zeynel Abidin Tas ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Female Rats ◽

Stress Index ◽

Control Group ◽

Vaginal Smear ◽

Therapeutic Effects ◽

Ovary Syndrome ◽

Pcos Group

Objective: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. Methods: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. Results: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). Conclusion: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

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Increased micronucleus frequencies in peripheral blood lymphocytes in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.02117 ◽

2006 ◽

Vol 154 (4) ◽

pp. 563-568 ◽

Cited By ~ 22

Author(s):

Elif Yesilada ◽

Ibrahim Sahin ◽

Hamdi Ozcan ◽

Ibrahim Halil Yildirim ◽

Saim Yologlu ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Genomic Instability ◽

Polycystic Ovary ◽

Peripheral Blood Lymphocytes ◽

Sex Hormone Binding Globulin ◽

Control Group ◽

Total Testosterone ◽

Ovary Syndrome ◽

Insulin Levels ◽

Pcos Group

Objective: We aimed to assess possible genomic instability in women with polycystic ovary syndrome (PCOS). Design: The frequency of micronuclei in cultured peripheral lymphocytes was used as a biomarker of genomic instability in somatic cells. Methods: Nineteen women, diagnosed with PCOS and 19 healthy female volunteers of corresponding ages and body-mass index (BMI) were included in the study. Micronuclei frequencies were assessed in cytokinesis-blocked lymphocytes. Results: The frequency of micronucleated cells (per thousand) was 9.00 (5.00) (interquartile range in parentheses) for patient group and 3.0 (3.0) for the control group (P < 0.0001, Mann-Whitney U-test). The serum levels of follicle-stimulating hormone (FSH), estradiol, prolactin, glucose and dehydroepiandrosterone sulfate (DHEAS) and the homeostasis model of assessment of insulin resistance (HOMA-IR) were not different between the two groups (P > 0.05). Serum total testosterone, luteinizing hormone (LH) and insulin levels and hirsutism score in the PCOS group were significantly (P = 0.007, P < 0.0001, P = 0.009 and P < 0.0001 respectively) higher than those of the control group (2.3 (2.1) nmol/l vs 1.7 (0.4) nmol/l; 8.5 (5.88) mU/ml vs 4.8 (4.4) mU/ml; 6.8 (5.1) μU/ml vs 9.7 (4.2) μU/ml; 19.5 (6.5) vs 4.0 (2.5) respectively). However, the mean level of sex hormone-binding globulin (SHBG) in PCOS group was significantly (P = 0.004) lower than in control group (36.4(22.6) nmol/l vs 48.6(25.2) nmol/l respectively). Conclusion: These findings suggest that women with PCOS have a high incidence of genomic instability, and this condition is positively correlated with the hirsutism score, BMI, LH and serum total testosterone and insulin levels, and is negatively correlated with SHBG.

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