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Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study.

ABSTRACT: Purpose:Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder that is characterized by disturbances in ovarian blood flow and angiogenesis. The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) serum levels with the body mass index (BMI) in patients with PCOS compared with healthy subjects. Methods:The study was conducted with 80 subjects in 3 PCOS groups, including normal weight, overweight, and obese PCOS groups, and a control group of healthy subjects (n=20). The participants in all groups completed a questionnaire comprising sociodemographic and obstetric questions. The PCOS diagnosis in the study subjects was confirmed based on the Rotterdam criteria, BMI was determined according to the World Health Organization guidelines, and the lipid accumulation product index was calculated for all groups. Venous blood samples were collected from all participants after fasting to measure the serum levels of fasting blood glucose (FBG), lipids, insulin, VEGF, TSP-1, and leptin. Results:Our findings showed that the serum VEGF level was significantly higher in the normal BMI PCOS group than that in the control group (P=0.03), and the TSP-1 level was significantly lower in the obese PCOS group than that in the control group (P=0.04). Conclusions:Our study demonstrated that alterations in VEGF and TSP-1 concentrations are dependent on BMI. Because abnormal ovarian angiogenesis is considered to be the main feature of PCOS, the study of ovarian angiogenic imbalance is proposed as a new tool for PCOS diagnosis and management.

SUBMITTER: Tahergorabi Z

PROVIDER: S-EPMC6856488 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study.

Tahergorabi Zoya Z Salmani Fatemeh F Jonaidabad Samira Hooshmand SH Behdani Bahere B Yazdi Parisa P Zardast Mahmoud M Moodi Mitra M

Obstetrics & gynecology science 20191014 6

<h4>Purpose</h4>Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder that is characterized by disturbances in ovarian blood flow and angiogenesis. The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) serum levels with the body mass index (BMI) in patients with PCOS compared with healthy subjects.<h4>Methods</h4>The study was conducted with 80 subjects in 3 PCOS groups, including normal weight, overweigh ...[more]

PMID: 31777738

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Project description:Study questionWhat are the causal relationships between polycystic ovary syndrome (PCOS) and body mass index (BMI)?Summary answerBidirectional Mendelian randomization analyses suggest that increased BMI is causal for PCOS while the reverse is not the case.What is known alreadyThe contribution of obesity to the pathogenesis of PCOS is controversial. To date, published genetic studies addressing this question have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with body mass index (BMI).Study design, size, durationThis cross-sectional Mendelian randomization (MR) and genetic association study was conducted in 750 individuals of European origin and with PCOS and 1567 BMI-matched controls.Participants/materials, setting, methodsCases and controls were matched for BMI as well as for distribution of weight categories (normal weight, overweight, obese). Two-sample MR using inverse variance weighting (IVW) was conducted using a 92-SNP instrument variable for BMI with PCOS as the outcome, followed by two-sample MR with a 16-SNP instrument variable for PCOS with BMI as the outcome. Sensitivity analyses included MR-Egger and maximum likelihood methods. Secondary analyses assessed associations of genetic risk scores and individual SNPs with PCOS, BMI and quantitative androgen-related and glucose homeostasis-related traits.Main results and the role of chanceEach standard deviation genetically higher BMI was associated with a 4.89 (95% CI 1.46-16.32) higher odds of PCOS. Conversely, genetic risk of PCOS did not influence BMI. Sensitivity analyses yielded directionally consistent results. The genetic risk score of 92 BMI SNPs was associated with the diagnosis of PCOS (OR 1.043, 95% CI 1.009-1.078, P = 0.012). Of the 92 BMI risk variants evaluated, none were associated individually with PCOS after considering multiple testing. The association of FTO SNP rs1421085 with BMI was stronger in women with PCOS (β = 0.071, P = 0.0006) than in controls (β = 0.046, P = 0.065).Limitations, reasons for cautionThe current sample size, while providing good power for MR and genetic risk score analyses, had limited power to demonstrate association of individual SNPs with PCOS. Cases and controls were not matched for age; however, this was mitigated by adjusting analyses for age. Dietary and lifestyle data, which could have been used to explore the greater association of the FTO SNP with BMI in women with PCOS, was not available.Wider implications of the findingsIncreasing BMI appears to be causal for PCOS but having PCOS does not appear to affect BMI. This study used the most comprehensive set of SNPs for BMI currently available. Prior studies using fewer SNPs had yielded conflicting results and may have been confounded because cases and controls were not matched for weight categories. The current results highlight the potential utility of weight management in the prevention and treatment of PCOS.Study funding/competing interest(s)National Institutes of Health Grants R01-HD29364 and K24-HD01346 (to R.A.), Grant R01-DK79888 (to M.O.G.), Grant U54-HD034449 (to R.S.L.), Grant U19-HL069757 (to R.M.K.). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare.Trial registration numberN/A.

Project description:Background: Recent reports have highlighted the role of monosaccharide biosynthesis in the pathogenesis of polycystic ovary syndrome (PCOS), suggesting that these processes may serve as a biomarker in PCOS. Mannose is the main monosaccharide for protein glycosylation in mammals; however, the correlation between mannose and PCOS remains largely unknown. Materials and Methods: A total of 132 Chinese Han women were recruited at Shengjing Hospital of China Medical University. Mannose levels were measured in serum samples collected from 71 patients with PCOS (29 lean, 42 obese) and 61 control subjects (28 lean, 33 obese). Receiver operating characteristics (ROC) curves were prepared to compare the diagnostic performance of mannose and hormonal parameters, individually or in combination. Multivariate logistic regression analysis was used to assess whether serum mannose levels were associated with PCOS after adjusting for other co-variables. Results: We showed that serum mannose levels were significantly increased in PCOS patients compared with control subjects regardless of obese status, and hyperandrogenic PCOS patients had higher serum mannose levels than normo-androgenic PCOS and control subjects. In addition, serum mannose levels were significantly correlated with serum androgen levels. Mannose had an area under the curve (AUC) of 73% at a cutoff value of 225.79 ng/mL with a sensitivity of 66.2% and specificity of 73.8% for predicting PCOS. There were no differences between mannose, total testosterone, free testosterone, or dehydroepiandrosterone sulfate in the reliability of predicting PCOS using the method outlined by Hanley and McNeil. Combining mannose and total testosterone resulted in a higher AUC of 83.3%, and had moderate sensitivity (78.9%) and specificity (77%) for predicting PCOS. The positive and negative predictive values were 80% and 75.8%, respectively. Multivariate logistic regression revealed that higher serum mannose levels were strongly associated with an increased risk of PCOS (P = 0.016; odds ratio, 5.623; 95% confidence interval, 1.371-23.070). Conclusion: Taken together, substantially elevated serum mannose levels are significantly associated with PCOS, highlighting the importance of further research into the role of mannose in the pathogenesis of PCOS.

Project description:BackgroundWomen who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes.MethodsFor the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes.ResultsFORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >.05).ConclusionThe effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.

Dataset Information

Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study.

Publications

Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study.

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