Polycystic ovary syndrome,adipose tissue and metabolic syndrome

Purpose

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD).

Methods

A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulinresistance, and metabolic syndrome. Original articles, reviews, and meta-analysis were included.

Results

PCOS women are prone to visceral fat hypertrophy in the presence of androgen excess and the presence of these conditions is related to insulin resistance and worsens the PCO phenotype. Disturbed secretion of many adipocyte-derived substances (adipokines) is associated with chronic low-grade inflammation and contributes to insulin resistance. Abdominal obesity and insulin resistance stimulate ovarian and adrenal androgen production, and may further increase abdominal obesity and inflammation, thus creating a vicious cycle.

Conclusion

The high prevalence of metabolic disorders mainly related to insulin resistance and CVD risk factors in women with PCOS highlight the need for early lifestyle changes for reducing metabolic risks in these patients.

     

Ameliorative effects of rutin against metabolic,biochemical and hormonal disturbances in polycystic ovary syndrome in rats

Background

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The study was commenced to assess the favorable effects of Rutin against metabolic, biochemical, histological, and androgenic aspects of polycystic ovary syndrome in rats.

Methods

Female Sprague-Dawley rats were administered letrozole (1 mg/kg) per orally (p.o) for a period of 21 days for the induction of PCOS, followed by dose of rutin (100 mg/kg and 150 mg/kg, p.o) for 15 days using 0.5% w/v CMC as vehicle. Metformin was also given as a standard control to one of the rat groups.Serum estradiol, progesterone, testosterone, serum lipid parameters, CRP and glucose levels were evaluated. Furthermore, antioxidant activity was tested using superoxide dismutase, catalase, glutathione per-oxidase and reactive-oxygen species level.

Results

Rutin flavonoid had a dose-dependent effect on androgenic levels depicting more recovery in the rutin-I treated group, while rutin-II treated groups showed better antioxidant and lipid profiles as compared with PCOS groups. A decrease in the value of C reactive protein (CRP) and a restoration in the proportion of estrous phase smears were observed in the rutin treated groups. Histopathological examination of ovary revealed a significant decrease in the number of cystic follicles in post treated groups. The effects observed with rutin were moderately similar to that with standard metformin, a widely used treatment drug for PCOS.

Conclusion

The study provides evidence for the potential ameliorative effects of rutin against clinical and biochemical features of PCOS.

     

Association study of <Emphasis Type="Italic">HNF1A</Emphasis> in women with polycystic ovary syndrome

Purpose

This study aims to ascertain whether an association exists between hepatocyte nuclear factor 1 alpha (HNF1A) and polycystic ovary syndrome (PCOS).

Methods

One thousand one hundred thirty-eight PCOS and 1125 healthy control Han Chinese women were recruited from Reproductive Hospital Affiliated to Shandong University. Serum hormone, blood lipid level, and genomic DNA were obtained from the peripheral blood for this research. Two single-nucleotide polymorphisms (SNPs)—rs2393791 and rs7305618—located in HNF1A were genotyped using the Sequenom MassARRAY system.

Results

The allele frequencies of SNP rs7305618 had significant differences between PCOS patients and controls after adjusting for age and BMI (p = 0.023). Besides, PCOS patients carrying the rs7305618 CC genotype shown a higher testosterone level than the patients with CT + TT genotypes after being adjusted by age and BMI (p = 0.019).

Conclusions

A SNP located in the HNF1A gene is associated with PCOS among Han Chinese women. This suggested that variations in HNF1A might confer risk for PCOS.

     

Umwelteinflüsse beim polyzystischen Ovarsyndrom

Background

With a prevalence of 6–20?%, polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies among fertile women. It is characterized by hyperandrogenism and chronic anovulation and is highly associated with insulin resistance. Women with PCOS suffer from menstrual irregularity resulting probably in subfertility and from hirsutism, acne, and androgenetic alopecia. Furthermore, obesity is common in PCOS. Women with PCOS report a significant decrease in quality of life. Multiple factors are involved in the pathophysiology of PCOS. Besides a genetic background, environmental factors seem to influence development.

Aim

This article outlines the role of selected environmental factors in the pathophysiology of PCOS and describes the influence of intrauterine exposure to androgens, obesity, and endocrine disruptors like bisphenol A (BPA) on the PCOS phenotype.

Results and discussion

Intrauterine exposure to androgen excess due to hyperandrogenism of the mother may lead to the development of the PCOS phenotype including metabolic derangements. Obesity does not seem to cause PCOS, but is highly associated with a more severe phenotype of PCOS and aggravates metabolic risks associated with PCOS. BPA may enhance androgen synthesis and activity.

     

4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with polycystic ovary syndrome in Chinese patients: a meta-analysis

Purpose

To date, case–control studies on the association between a single-nucleotide polymorphism (SNP) in the plasminogen activator inhibitor-1 (PAI-1) gene and polycystic ovary syndrome (PCOS) have provided controversial results.

Methods

The electronic databases PubMed, Embase, Web of Science, and CNKI (China National Knowledge Infrastructure) were searched for studies to include in the present meta-analysis.

Results

The fixed effects and random effects models showed that the 4G allele was associated with a risk of PCOS compared with the 5G allele in Chinese patients (OR = 2.05; 95 % CI = 1.56–2.69), but not in Caucasian patients (OR = 1.05; 95 % CI = 0.81–1.37). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast.

Conclusion

Our pooled data suggest evidence for a major role of PAI-1 gene 4G/5G polymorphism in the pathogenesis of PCOS among Chinese patients.

     

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS

Purpose

The pro-inflammatory advanced glycation end products (AGEs) and their anti-inflammatory soluble receptors, sRAGE, play a role in the pathogenesis of PCOS. There is a correlation between vitamin D (vit D) and sRAGE in the serum, whereby vit D replacement increases serum sRAGE levels in women with PCOS, thus incurring a protective anti-inflammatory role.

Objective

This study aims to compare levels of sRAGE, N-carboxymethyl-lysine (CML; one of the AGEs), and 25-hydroxy-vit D in the follicular fluid (FF) of women with or without PCOS, and to evaluate the correlation between sRAGE and 25-hydroxy-vit D in the FF.

Material and methods

Women with (n = 12) or without (n = 13) PCOS who underwent IVF were prospectively enrolled.

Results

Women with PCOS had significantly higher anti-Mullerian hormone levels, higher number of total retrieved and mature oocytes, and higher number of day 3 and day 5 embryos formed. Compared to women without PCOS, women with PCOS had significantly lower FF sRAGE levels. In women with PCOS, in women without PCOS, and in all participants together, there was a significant positive correlation between sRAGE and 25-hydroxy-vit D. sRAGE positively correlated with CML in women without PCOS but not in women with PCOS.

Conclusions

In women with PCOS, the low ovarian levels of the anti-inflammatory sRAGE suggest that sRAGE could represent a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS. Whether there is a direct causal relationship between sRAGE and vit D in the ovaries remains to be determined.

     

Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients

Background

Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease.

Methods

This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group.

Results

Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR.

Conclusions

Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

     

Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

Background

Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women.

Methods

The study included 119 non-obese patients with PCOS (age: 22.2?±?4.1y, BMI:22.5?±?3.1?kg/m²), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured.

Results

T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p?<?0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p?<?0.05). All subphenotypes had similar basal and AUC values for cortisol.

Conclusion

PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

     

Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants in polycystic ovary syndrome

Purpose

Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women.

Methods

A retrospective case–control study, involving 203 women with PCOS, and 211 age- and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).

Results

Significantly lower frequencies of heterozygous LHCGR rs7371084 and FSHR rs11692782 genotype carriers were seen between women with PCOS vs. controls, and increased frequency of heterozygous homozygous LHCGR rs4953616 genotype carriers were detected between women with PCOS compared to control women. Limited linkage disequilibrium was noted among LHCGR and FSHR SNPs, and 2 blocks were constructed: the first (Block 1) spanning 61 kb contained the six tested LHCGR SNPs, and the second (Block 2) spanning 298 kb contained four of the five tested FSHR SNPs. Higher frequency of LHCGR GTCAAG haplotype was seen in women with PCOS compared to controls; the frequencies of the remaining LHCGR haplotypes, and all FSHR haplotypes were similar between cases and controls.

Conclusion

This is the first study to confirm the association of novel LHCGR (rs7371084, rs4953616) and FSHR (rs11692782) SNPs with PCOS. The differential association of LHCGR and FSHR variants with PCOS confirms the racial/ethnic contribution to their association with PCOS.

     

Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome

Purpose

To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency.

Methods

Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18–40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable.

Results

Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P?=?0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P?=?0.02).

Conclusions

In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

     

Practical Approach to the PCOS Patient

Purpose of Review

The purpose of this review is to provide an overview of polycystic ovary syndrome (PCOS) with a discussion on our current understanding of the pathophysiology and sequela of this syndrome. A diagnostic algorithm, as well as the challenges clinicians may face when evaluating these patients is also included. Clinical treatment strategies for fertility and non-fertility PCOS patients are described in detail.

Recent Findings

Recent discussions on the inaccuracies and lack of standardization for the measurement of androgens, both clinically and chemically, are highlighted. A meta-analysis and a randomized controlled trial evaluating the efficacy of commonly used ovulation induction medications are also included along with recommendations from national committee reports and consensus opinions.

Summary

PCOS is recognized as one of the most common endocrinopathies in women worldwide which continues to attract increased attention and research. Inheritance patterns are multifactorial and may be influenced trans-generationally due to the epigenetic influence of metabolic syndrome. Women with PCOS are at an increased risk of long-term health consequences for which they should be appropriately monitored and treated, in order to decrease the overall morbidity associated with this syndrome. Treatment should be individualized based on the phenotypic presentation of the patient as well as their fertility desires. For some patients, referral to a specialist and multidisciplinary care may be required.

     

Endokrine Disruptoren

Background

We are constantly exposed to a cocktail of substances that could act as endocrine disruptors. Experiences with substances like diethylstilbestrol have proven that the female reproductive organs can be damaged irreversibly by exposure to exogenous hormones during sensitive developmental stages. It is therefore necessary to address this important issue.

Objectives

The adverse effects of endocrine disruptors on the female reproductive organs are summarized. In addition, special aspects of the toxicity of these substances are identified.

Materials and methods

Selected literature on the adverse effects of endocrine disruptors on female reproductive organs was screened and evaluated.

Results

The majority of findings on the adverse effects of endocrine disruptors on the female organism are derived from animal studies. Observed toxicities affect all female reproductive organs (ovaries, uterus, vagina) and the timing of sexual maturation. The effects include polycystic ovary syndrome, altered cycliscity, endometriosis, pregnancy complications, and uterine fibroids. Importantly, the damage does not usually manifest directly after exposition, but after a considerable temporal interval.

Conclusion

Exposure to endocrine disrupters can damage the female reproductive organs. Embryos, fetuses, and newborn babies are much more sensitive than adult women. The extent to which our health is affected by the continuous intake of low quantities of various endocrine disrupters from the environment is very difficult to estimate. Endocrine disruptors therefore remain in the focus of toxicological research.

     

Pulsatile Gonadotropin-Releasing-Hormon-Behandlung

Background

Pulsatile gonadotropin-releasing hormone (GnRH) therapy is an option for ovulation induction in patients with central hypothalamic functional disorders, which is often only initiated as second-line treatment due to the alleged effort involved in treatment.

Objective

The indications, course and results of a standardized pulsatile GnRH treatment are presented in order to demonstrate the value of this form of treatment.

Results

In addition to the classical indications for hypothalamic amenorrhea, pulsatile GnRH treatment can also be used for drug-resistent hyperprolactinemia and some mixed forms of polycystic ovarian syndrome (PCOS). Current data demonstrate that pulsatile GnRH stimulation is one of the most effective forms of treatment in reproductive medicine, particularly in patients with hypothalamic amenorrhea and infertility.

Discussion

In cases with clear indications, pulsatile GnRH should be the first choice treatment for ovarian stimulation.

     

Complete protection against cryodamage of cryopreserved whole bovine and human ovaries using DMSO as a cryoprotectant

Purpose

This study aims to determine the optimal cryopreservation protocol for whole ovaries intended for preservation of fertility in women.

Methods

We investigated the optimal cryopreservation procedure for whole ovaries in a bovine model. The following parameters were investigated to determine their effect on ovarian tissue viability: type of cryoprotectant, administration route of the cryoprotectant (perfusion and/or submersion), and the maximum tolerable interval between death of the animal and start of the cryopreservation process. The resulting optimal cryopreservation procedure for bovine ovaries was subsequently tested on human ovaries. In vitro glucose uptake, histology, and immunohistochemistry were used to assess the integrity of the ovarian tissue.

Results

Starting the cryopreservation procedure (including perfusion with and submersion in DMSO) within 10–15 min after death of the animal proved critical, resulting in a 90–100% protection level against cryodamage. When cryopreserving human ovaries using the same protocol, over 95% protection against cryodamage was observed on all tissue levels. In addition, no apparent morphological damage to either the follicles or the vascular endothelium was observed.

Conclusion

Our findings suggest that using the optimized protocol presented in this paper allows good cryopreservation of whole human ovaries and represents an important step in considering whole ovary autotransplantation for clinically applied fertility preservation.

     

Follicular fluid soluble receptor for advanced glycation endproducts (sRAGE): a potential protective role in polycystic ovary syndrome

Purpose

To explore the relationships between the soluble receptor for advanced glycation endproducts (sRAGE) and the outcome parameters following in vitro fertilization-embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS) and investigate the protective effect of sRAGE in PCOS development regarding inflammation.

Methods

We conducted a prospective analysis of a subsample of 74 participants from the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University. We quantified sRAGE, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF-α), interleukelin-6 (IL-6), and C-reactive protein (CPR) protein levels in the follicular fluid from 39 PCOS and 35 non-PCOS reproductive-age women. sRAGE and VEGF, TNF-α, IL-6, and CRP in follicular fluid aspirated without blood were measured by ELISA.

Results

sRAGE concentrations in the follicular fluid were significantly lower in the PCOS group compared to those in the control group, while VEGF, TNF-α, IL-6, and CRP concentrations were significantly higher in the PCOS group than in the control group (P?<?0.05). sRAGE was significantly, inversely correlated with the total dose of gonadotropin (Gn) in the PCOS group undergoing IVF treatment (r?=??0.451, P?=?0.004). After adjusting for age and Gn dose (in international units used per cycle), sRAGE protein levels in the follicular fluid were significantly, inversely related to VEGF (r?=??0.378, P?=?0.018), TNF-α (r?=??0.450, P?=?0.004), IL-6 (r?=??0.455, P?=?0.004), and CRP (r?=??0.375, P?=?0.019).

Conclusion

sRAGE in the follicular fluid might exert a protective effect against the inflammatory action of PCOS development.

     

Unilateral or bilateral laparoscopic ovarian drilling in polycystic ovary syndrome: a meta-analysis of randomized trials

Purpose

This systematic review and meta-analysis aimed to compare the effectiveness of unilateral vs. bilateral laparoscopic ovarian drilling (ULOD vs. BLOD) for improving fertility outcomes in infertile women with clomiphene-resistant polycystic ovary syndrome (PCOS) as well as its effect on ovarian reserve.

Methods

Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov, and CENTRAL databases from January 1984 to January 2017. Only randomized trials comparing ULOD with BLOD were included. The PRISMA Statement was followed. Main outcomes were ovulation and clinical pregnancy rates per woman randomized. Secondary outcomes were; live birth and miscarriage rates as well as postoperative serum anti-mullerian hormone (AMH) concentration and antral follicle count (AFC). Quality assessment was performed by the Cochrane Collaboration risk of bias tool.

Results

Eight eligible trials (484 women) were analyzed. No significant difference was found in rates of ovulation (OR 0.73; 95% CI 0.47–1.11), clinical pregnancy (OR 0.56; 95% CI 0.22–1.41), live birth (OR 0.77; 95% CI 0.28–2.10), or miscarriage (OR 0.90; 95% CI 0.33–2.84) when ULOD was compared with BLOD. The reduction in AMH was comparable between the two procedures (MD 0.64 ng/ml; 95% CI ? 0.08 to 1.36). A significantly higher AFC at 6-month follow-up was found with dose-adjusted ULOD (MD 2.20; 95% CI 1.01–3.39).

Conclusions

After carefully weighing up the well-known benefits of BLOD against a potential risk to ovarian reserve, clinicians could be advised to offer the fixed-dose ULOD to their infertile patients with clomiphene-resistant PCOS. This is concordant with the “primum non nocere” principal if LOD will be envisaged.

     

Anti-Müllerian hormone gene polymorphism is associated with androgen levels in Chinese polycystic ovary syndrome patients with insulin resistance

Purpose

The objective of the study was to investigate whether genetic polymorphisms of the anti-Müllerian hormone (AMH) and its specific receptor anti-Müllerian hormone type II receptor (AMHRII) were associated with the hormone disorder and phenotype of polycystic ovary syndrome (PCOS).

Methods

This case-control study included 141 PCOS patients and 123 normal women. Two polymorphisms of AMH and AMHRII and the clinical characteristics of participants such as body mass index (BMI), serum luteinizing hormone (LH), estradiol levels (E₂), total testosterone levels (T), and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed with the case-control sample. Gene–gene interactions of AMH and AMHRII genes were analyzed based multifactor-dimensionality reduction method.

Results

A significant difference of AMH gene polymorphisms were observed in IR-PCOS women and controls. The AMH and AMHRII gene polymorphisms were not found a significant difference in non-IR-PCOS and normal groups. To IR-PCOS women, genotypes of AMH were closely related to the serum levels of LH (P?=?0.000), testosterone (P?=?0.000) and HOMA-IR (P?=?0.038), while in the non-IR-PCOS and normal groups, no relationship was found. No impact of AMH and AMHRII gene–gene interactions was demonstrated.

Conclusions

Our research suggests that the diversity of AMH genotypes in the AMH signal pathway may be connected with the susceptibility and phenotype of PCOS with insulin resistance.

     

Intrafollicular fibroblast growth factor 13 in polycystic ovary syndrome: relationship with androgen levels and oocyte developmental competence

Background

Fibroblast growth factor 13 (FGF13) is one of the most highly expressed FGF family members in adult mouse ovary. However, its precise roles in ovarian function remain largely unknown. We sought to evaluate the associations between FGF13 in follicular fluid and oocyte developmental competence in patients with polycystic ovary syndrome (PCOS).

Methods

A cross-sectional study was conducted on 43 patients with PCOS and 32 non-PCOS patients who underwent in vitro fertilization/intracytoplasmic sperm injection treatments. The highest quartiles of follicular fluid (FF)-FGF13 (≥117.51 pg/mL) and FF-total testosterone (FF-TT) (≥51.90 nmol/L) were defined as “elevated” FF-FGF13 levels and “elevated” FF-TT levels, respectively.

Results

The levels of FF-FGF13 were skewed, with a median of 82.97 pg/mL (59.79–117.51 pg/mL) in 75 patients. The prevalence of elevated FF-TT levels was significantly higher in the PCOS patients with elevated FF-FGF13 levels than in those without (64.3% vs. 35.7%, adjusted P?=?0.0096). FF-TT and increased ovarian volume (>?10 mL for one or both ovaries) were positively correlated with FF-FGF13 in PCOS patients (r?=?0.37, P?=?0.013; r?=?0.33, P?=?0.032). A negative association was evident between FF-FGF13 and the MII oocyte rate in the multiple linear regression analysis (β?=???0.10, SE?=?0.045, adjusted P?=?0.027). However, the associations were not evident in the non-PCOS patients.

Conclusions

Our study suggests the presence of intrafollicular FGF13 in PCOS patients and implies that FGF13 might be involved in the pathophysiological process of PCOS.

     

Hippo signaling in the ovary and polycystic ovarian syndrome

Purpose

To provide a commentary on our understanding of the role that the Hippo signaling pathway may play in patients with polycystic ovarian syndrome (PCOS) and how this understanding may impact the diagnosis of PCOS.

Methods

We assessed publications discussing the role of the Hippo signaling pathway in the ovary. In particular, we discuss how Hippo signaling disruption after ovarian fragmentation, combined with treating ovarian fragments with phosphatase and tensin homolog (PTEN) inhibitors and phosphoinositide-3-kinase stimulators to augment AKT signaling, has been used in treatment of patients with primary ovarian insufficiency. Furthermore, we discuss our own data on variations in Hippo signaling pathway gene expression in cumulus cells isolated from women undergoing IVF with a previous diagnosis of PCOS.

Results and conclusions

Aberrant Hippo signaling in PCOS patients is likely a contributing mechanism to the multifactorial etiology of the disease. Given the challenge of discerning the underlying etiology of oligo-ovulation in some patients, especially those with normal body mass indices, and the need for customized stimulation protocols for PCOS patients who have an increased risk of over-response and higher percentage of immature oocyte yield, it is important to identify these patients prior to treatment. Hippo gene expression fingerprints could potentially be used to more accurately define patients with PCOS. Additionally, targeting this pathway with pharmacologic agents could lead to non-surgical therapeutic options for PCOS.

     

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome

Purpose

The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin.

Methods

We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS—13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers.

Results

Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003).

Conclusions

Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.