non-PCOS Patients Research Articles

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR.MethodsA total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed.ResultsFirst, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS.ConclusionsElevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

CYP19A1 Gene Expression in Patients with Polycystic Ovarian Syndrome.

Context:Polycystic ovarian syndrome (PCOS) is a common endocrine system disorder among the women of reproductive age, yet the etiology of PCOS remains unclear. Infertility in females with PCOS can be caused by anovulation, high luteinizing hormone levels, and hyperandrogenism.Aims:This research analyzed the role of the aromatase gene (CYP19A1) in PCOS pathogenesis.Settings and Design:This study used an observational, cross-sectional design.Subjects and Methods:A total of 110 research participants (55 PCOS patients and 55 non-PCOS patients) were included in the study.Statistical Analysis Used:A real-time quantitative polymerase chain reaction was used to analyze the mRNA expression for aromatase in granulosa cells.Results:The relative expression of aromatase mRNA is lower in women with PCOS compared to those without PCOS (P < 0.05). Relative expression of CYP19A1 (aromatase) mRNA in PCOS group was 0.38 ± 0.25, whereas in non-PCOS group was 1.00 ± 0.00. The decline in aromatase activity contributes to an increase in testosterone level. This condition has a role in hyperandrogenism which is a typical characteristic of PCOS women. Granulosa cells in polycystic ovary undergo disturbance in the development and cannot respond to follicle-stimulating hormone (FSH) stimulation. Lack of stimulation of FSH causes induction inadequacy to aromatase enzyme activity in the aromatization process. The decline in FSH activity is caused by various factors that are associated with typical characteristics of PCOS.Conclusions:There is a decrease in the relative expression rate of granulosa cells’ aromatase mRNA in women with PCOS compared to the non-PCOS.

The Effect of Recombinant LH Addition to Recombinant FSH on Assisted Reproductive Technologies Outcomes in Overweight and Obese Patients without Polycystic Ovary Syndrome

Background: Obesity and overweight negatively affect fertility. Protocols need to be developed in ART treatments for obese and overweight women. Objectives: To investigate the effect of recombinant luteinizing hormone (rLH) addition to recombinant follicle stimulating hormone (rFSH) on treatment outcomes in assisted reproductive technologies (ART) cycles in obese and overweight women without polycystic ovary syndrome. Methods: This retrospective cohort study was carried out in Kocaeli University Faculty of Medicine, Assisted Reproductive Techniques Clinic between January 2016 and March 2019. To analyze the impact of rLH addition to rFSH in GnRH antagonist cycles in overweight and obese, the patients were divided into four groups according to body mass index (BMI) and gonadotropin type; Group 1: patients with BMI ≥ 25 stimulated with rFSH alone (n: 37), Group 2: patients with BMI ≥ 25 stimulated with rFSH + rLH (n: 37), Group 3: patients with BMI between 18.5 - 24.99 stimulated with rFSH alone (n: 33), Group 4: patients with BMI between 18.5 and 24.99 stimulated with rFSH + rLH (n: 30). Patients with polycystic ovary syndrome were excluded. Results: Basal LH levels were found to be significantly lower in obese and overweight patients compared to normoweight patients (p = 0.01). Grade 1 embryo ratio in obese and overweight patients was higher in rLH added obese group than in group LH not included (64.9%, p = 0.005). Ongoing pregnancy rates (OPR) in obese and overweight patients were significantly higher in rLH added group compared to rFSH only group (43.2% vs 18.9% respectively, p = 0.044). However, OPR did not differ significantly in rLH added and rFSH only groups in normoweight patients (p = 0.588). Conclusion: This study has shown that obese and overweight non-PCOS patients have lower endogenous LH levels. It has also shown that rLH supplementation in GnRH antagonist cycles in obese and overweight women improves embryo quality and ongoing pregnancy rates. However rLH addition to rFSH doesn’t seem to have a value in normoweight patients.

Correlation between follicular fluid sRAGE level and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation

To investigate the correlation between soluble receptor for advanced glycation end products (sRAGE) level in the follicular fluid and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation. Ninety non-PCOS patients underwent IVF/ICSI using a short-acting long protocol for ovarian stimulation with a GnRH agonist. For each patient, the level of sRAGE in the follicular fluid was measured by enzyme linked immunosorbent assay (ELISA), and the data including the clinical baseline state, hormone level, number of oocytes obtained and the fertilization rate were collected. Follicular fluid sRAGE level showed significant negative correlations with basal FSH level (P=0.0036) and Gn dose (P < 0.0001) and positive correlations with AFC (P < 0.0001), number of oocytes obtained (P < 0.0001), and the fertilization rate (P=0.0047). Follicular fluid sRAGE level was positively correlated with the number of oocytes obtained, and was significantly higher in cases with oocytes obtained above the target number (> 15) than in cases with oocytes obtained within the range of the target numbers (7-15) and below the target number (< 7) (P < 0.0001 and P=0.0012, respectively). Follicular fluid sRAGE level can reflect ovarian reserve function in non-PCOS patients, the number of oocytes obtained and the fertilization rate, and can thus predict ovarian responsiveness during controlled hyperstimulation in nonPCOS patients.

A Slower Age-Related Decline in Treatment Outcomes After the First Ovarian Stimulation for in vitro Fertilization in Women With Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) patients have a better ovarian reserve and age-related improvement in endocrine disturbances than non-PCOS patients. The effects of age on in vitro fertilization (IVF) treatment outcomes associated with cumulative live birth rate (CLBR) remain unclear.Objectives: To study the effect of age on CLBR after the first ovarian stimulation in IVF in PCOS patients.Method: This retrospective cohort study included 3,502 PCOS patients and 18,596 patients with tubal factor infertility, who underwent their first IVF cycles and subsequent frozen embryo transfer (ET) attempts. The primary outcome was CLBR associated with a single stimulation cycle and secondary outcomes included the implantation rate, clinical pregnancy rate, live birth rate (LBR), large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm birth (PTB) rate of fresh ET cycles.Results: PCOS patients over 40 years had a higher implantation rate (27.8 vs. 15.7%, P < 0.05), clinical pregnancy rate (51.4 vs. 26.1%, P < 0.05), LBR (42.3 vs. 18.2%, P < 0.05), and CLBR (50.0 vs. 21.5%, P < 0.05) than non-PCOS patients over 40 years. These rates were comparable between PCOS patients aged 35 to 40 years and those aged over 40 years (P = 0.263, 0.385, and 0.112, respectively). The changes in the implantation rate, clinical pregnancy rate, and CLBR by age were slower for PCOS patients than for non-PCOS patients (all P < 0.05). Among PCOS patients less than 35 years, BMI was negatively associated with CLBR [aOR: 0.961 (0.939–0.985); P < 0.05]; however, among PCOS patients over 35 years, instead of BMI (P = 0.353), age [aOR: 0.891 (0.803–0.990); P < 0.05] and the number of oocytes retrieved [aOR: 1.093 (1.002–1.078); P < 0.05] were significantly associated with CLBR. No significant differences in LGA, LGA, or PTB were detected between PCOS and non-PCOS patients over 35 years (all P > 0.05).Conclusions: The declines in treatment outcomes with age are slower for PCOS patients than for non-PCOS patients. For patients over 40 years, PCOS patients have reproductive advantages over non-PCOS patients. In contrast to younger PCOS patients (<35 years), older PCOS patients (≥35 years) may benefit less from taking time to lose weight before IVF treatment, and the immediate initiation of assisted reproductive treatment is essential.

Increased Expression of KISS1 and KISS1 Receptor in Human Granulosa Lutein Cells-Potential Pathogenesis of Polycystic Ovary Syndrome.

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Müllerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.

Age, body weight and ovarian function affect oocyte size and morphology in non-PCOS patients undergoing intracytoplasmic sperm injection (ICSI)

The size of oocytes was previously reported to be smaller in obese women with polycystic ovary syndrome (PCOS). In the present prospective cohort study, we sought to determine whether oocyte size and morphology are associated with patient characteristics in non-PCOS women. Oocyte and oolemmal diameter were measured, enlarged perivitelline space (PVS) and ooplasmic granulation were assessed in 308 MII oocytes from 77 IVF/ICSI couples. Statistical analysis was undertaken using SAS version 9.4 (SAS institute Inc., USA). Continuous values are presented as mean ± SD and compared using a two-sample t-test or Mann-Whitney U test as appropriate. Categorical parameters are presented as proportions and compared using a Fisher exact test. Logistic and linear regression models were used to control for the effect of age for categorical and continuous variables respectively. P-value < 0.05 was considered statistically significant. Patients presented with a mean age of 40.3±5.0 years, had a BMI of 25.1±6.1 kg/m2, median AMH levels of 0.6 ng/ml and produced a median of 4 oocytes. Mean total oocyte diameter was 163.2±7.4 μm (range 145.8–182.1 μm), while oolemmal diameter was 109.4±4.1 μm (range 98.5–122.3 μm). After adjusting for age and ovarian reserve increasing BMI was associated with decreased total oocyte diameter (p<0.05). Total oocyte diameter was also inversely associated with AMH levels (p = 0.03) and oocyte yield (p = 0.04). In contrast to total oocyte diameter, oolemmal diameter was not related to patient characteristics. Younger women and those with large oocyte yields demonstrated fewer oocytes with ooplasmic granulation (p<0.05 and p = 0.01). After adjustments for age, ooplasmic granulation was also less frequently observed in oocytes from women with higher AMH (p = 0.03) and increasing BMI (p<0.01). Fertilization was more likely in oocytes with larger oolemmal diameter (p = 0.008). Embryos from oocytes with larger total and ooplasmic diameters were more likely to be transferred or frozen (p = 0.004 and p = 0.01). In non-PCOS infertile women, BMI and ovarian function relate to total oocyte diameter. These results expand on previously observed associations between oocyte size and BMI in women with PCOS. They indicate the importance of detailed oocyte assessments, which may aid the currently used criteria for embryo selection and help to better understand how oocyte status is associated with later embryo development.

The role of Kisspeptin levels in polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovarian syndrome (PCOS) is a complex and not fully elucidated pathology. This prevalent endocrinopathy affects patients in reproductive age, impacts on estrogen-dependent diseases, as well as in infertility. In this context, Kisspeptin (KP) may be considered a potential biomarker for PCOS diagnosis and follow-up. Here, we aimed to verify the levels of KP in obese and non-obese patients with PCOS, their relationship with other hormones, in comparison to healthy controls. A systematic review and meta-analysis were performed according to the PRISMA guidelines. We searched MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science for eligible studies. A random effects model meta-analysis of standardized mean difference (SMD) was conducted and the I2 was used to assess heterogeneity. Meta-regression was conducted through mixed-effects model. A total of 12 studies were included, comprising 660 PCOS patients and 600 controls. The KP levels were lower in the control group (0.76: 0.17-1.35; 95% CI). In the subgroup analyses, patients were divided in non-overweight/obese (BMI < 25) and overweight/obese (BMI ≥ 25) groups. The meta-regression revealed a difference between the obese and non-obese groups (z = 2.81; p = 0.0050). PCOS patients showed higher KP levels than control, and obese non-PCOS patients also showed altered KP levels. All studies had poor descriptions of sample collection, pre-analytical and analytical procedures, which is critical considering structural characteristics of the KP molecule.

The role of Letrozole (LE) in controlled ovarian stimulation (COS) in patients at high risk to develop ovarian hyper stimulation syndrome (OHSS). A prospective randomized controlled pilot study

BackgroundRecently, it has been shown that PCOS patients with extremely high anti-Mullerian hormone (AMH) level are more likely to experience OHSS during IVF, compared to PCOS patients with lower AMH level. While recent data questioned the effect of Letrozole (LE) on the occurrence of OHSS in non-PCOS patients, it role in PCOS patients with very high AMH level was never investigated in a prospective manners. Hence, our main objective was to evaluate the clinical outcome of PCOS patients at very high risk for OHSS undergoing two different COS protocols (with or without LE). MethodsA prospective randomized controlled study (RCT) of 51 patients with specifically high levels of AMH undergoing one of two COS protocols. The control group (group A) consisted of 24 PCOS women who received low-dose gonadotropins using the multiple-dose GnRH-antagonist protocol, GnRH agonist-triggered and “freeze all”. The study group (group B) consisted of 24 women with PCOS who received the same protocol combined with LE. High risk criteria for OHSS were: PCOS patients with low BMI, young age, and extremely high level of serum AMH (inclusion criteria for AMH > 50 pmol/L). ResultsCumulative live birth rates per retrieval were similar in both groups. While no single case of severe OHSS was observed in, in the study group (group B), the rate of moderate and mild OHSS was 5 times lower compared to the control group (P < 0.05). ConclusionIn PCOS patients with extremely high AMH levels the LE co-administration to GnRH-Ant protocols results in reduced incidence of OHSS than conventional GnRH-Ant protocols. LE co-administration may prove to be highly effective in preventing OHSS, even in the women who are at high risk to these dangerous complications.

The impact of peak estradiol during controlled ovarian stimulation on the cumulative live birth rate of IVF/ICSI in non-PCOS patients.

The study aimed to investigate the impact of the peak E2 level during controlled ovarian hyperstimulation (COS) on the cumulative live birth rate (cLBR) in non-PCOS women with normal ovarian reserve. Women between 20 and 39 years were included. Donor cycles and patients who never experienced embryo transfer were excluded. Multivariable regression and smooth curve fitting were applied for statistical analysis. A total of 1141 patients were included. The mean age, basal AFC, peak E2 level, and number of retrieved oocyte were 30.0 ± 3.7years old, 16.8 ± 6.7, 3911.0 ± 1302.9pg/ml, and 13.6 ± 5.5, respectively. In the overall population of the cohort, cLBR, miscarriage rate, and preterm birth rate were 66.9%, 7.4%, and 13.7%, respectively. The results of multivariable regression analysis failed to show the impact of peak E2 on the cLBR [OR (95%CI) 0.995 (0.982, 1.009), P = 0.486]. However, the result of smooth curve fitting indicated that when the peak E2 was lower than 2185pg/ml, the cLBR increased about 12% with 100pg/ml increasing of the peak E2. When the peak E2 was higher than 6136pg/ml, the cLBR decreased about 10% with 100pg/ml increasing of the peak E2. We concluded that the peak E2 level on hCG trigger day is associated with the cLBR in a segmental pattern. There should be an appropriate range of the peak E2 level during COS to achieve a relative best cLBR in non-PCOS patients using stimulating protocol mainly based on GnRH agonist; however, the cutoff value must vary in different centers.

Impact of maternal ethnicity on pregnancy outcome in infertile women with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine pathology seen among women of reproductive age. The objective of the study is to investigate the impact that ethnic background has on pregnancy outcomes, including live birth rates in infertile women with PCOS going through IVF compared to women without PCOS. Retrospective cohort study in an academic IVF center. This study used a coded REDCap data set of 486 women, 18-45 years of age who underwent IVF and embryo transfer between 1/1/2010 and 12/31/2015 at an academic IVF Center after IRB approval (IRB 2015-0623). Patients underwent their 1st IVF cycle following progestogen withdrawal (norethindrone acetate) using GnRH agonist or antagonist protocols with mixed gonadotropins and demographic data, including race and ethnicity was obtained. Data collected during the IVF process included peak estradiol, number of mature oocytes, fertilization rate, number of top quality embryos on Day 3 of development, number of embryos transferred, implantation rate, clinical pregnancy rate, live birth rate, clinical miscarriage rate, and ectopic pregnancy rate. In women, whose pregnancy resulted in a live birth, additional maternal and neonatal variables were collected, including estimated gestational age (EGA) at delivery, mode of delivery, and weight at birth. Using R analytics software, data was analyzed using logistic regression and linear models. For logistic regression, the estimated coefficient was the log-odds-ratio. A significant p value was considered <0.05. Of the 486 initial women, 360 women were included in the final analysis. Only women with known/reported ethnicity were included. Not Hispanic is the referent cohort for ethnicity and non-PCOS is the referent group when comparing PCOS status. There was no significant difference found for implantation rate (p=0.53) and pregnancy rate (p=0.99) when comparing women without PCOs with the women with PCOS. When taking into account the ethnicity factor in PCOS and the women who conceived and had a live birth, there was no significant difference between being Hispanic with PCOs and the referent non-Hispanic group. However, when evaluating women who started the IVF cycle, women with PCOS are less likely to have a pregnancy that leads to a live birth compared to women without PCOS (p=0.046). Being Hispanic by itself does not seem to affect live birth (p= 0.81). Hispanic women with PCOS have the same probability of having a vaginal delivery compared to the referent group (p=0.935). Women with PCOS are more likely to deliver ∼2 weeks earlier than non-PCOS patients (p=0.038). Being Hispanic and having PCOS did not affect the EGA at delivery (p= 0.83) or affected fetal weight compared to the referent group (p=0.58). This pilot study did not find a significant difference in most of the variables studied comparing Hispanic PCOS women with non-Hispanic women without PCOS. However, further studies with a larger number of subjects are needed to assess the impact of ethnicity and PCOS on IVF pregnancy outcomes.

The association between dietary antioxidants, oxidative stress markers, abdominal obesity and poly-cystic ovary syndrome: A case control study

In this case-control study, 60 patients with Polycystic ovary syndrome (PCOS) referred to the Nursing and Midwifery Center of Khorramabad, were selected as the case group and 90 non-PCOS patients as the control group. Demographic information and anthropometric indices of each person were collected. The Food Frequency Questionnaire (FFQ) and International Physical Activity Questionnaire (IPAQ) were completed. After at least 12 h of fasting, 7 mL of blood samples were taken from the patients. There was no statistically significant difference observed in the mean of the total antioxidant capacity (TAC) between the two groups. However, a statistically significant difference was found between the two groups in terms of malondialdehyde (MDA) and some dietary antioxidants levels (mean in case group: vit C = 34/2 mg, vit E = 7/7 mg, Se = 84/6 µg, Zn = 7/5 mg, beta-carotene = 762/8 µg, mean in control group: vit C = 72/5 mg, vit E = 10/6 mg, Se = 91/0 µg, Zn = 10/6 mg, beta-carotene = 1609/5 µg).IMPACT STATEMENTWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is one of the most common endocrine abnormalities and is considered as the main cause of infertility. Some studies have evaluated the link between dietary intakes and oxidative stress markers in PCOS patients. It is well known that about 40–50% of individuals with PCOS are obese and that leads to an increase in lipid catabolism and production of free radicals and oxidative stress.What the results of this study add? The aim of the present study was to compare the level of dietary antioxidants and oxidative stress markers including TAC, MDA and abdominal obesity prevalence in PCOS patients with healthy individuals.What the implications are of these findings for clinical practice and/or further research? We hope that our study can be influential in the field of PCOS. Furthermore, our findings have indicated a statistically significant difference between the two groups in terms of MDA and some dietary antioxidants levels. This result might be encouraging in using antioxidant in patients with PCOS.

Quality of life among infertile PCOS patients.

To investigate whether quality of life differs between PCOS and non-PCOS infertile women. Two questionnaire forms of quality of life (PCOSQ, SF-36) were given to 238 women. Patients were asked to answer all of the questions in both of the questionnaires. Of these 238 women, only 49 infertile PCOS patients, 47 infertile non-PCOS patients and 62 fertile PCOS patients fılled the forms completely. Both PCOSQ and SF-36 scores are lowest in infertile PCOS group. Although total PCOSQ score of infertile non-PCOS group was better than non-infertile PCOS and fertile PCOS groups; there was trend for lower scores when infertility is added on PCOS status. The quality of life is lowest among infertile PCOS women. Both PCOS and infertility as individual factors may have negative impact in quality of life of reproductive age women.

2077-P: Effect of Laparoscopic Sleeve Gastrectomy on Sex Hormone Level and Ovarian Volume in Female Obesity with PCOS

Objective: This study was designed to examine changes in body fat distribution after laparoscopic sleeve gastrectomy (LSG) and to confirm whether these changes are correlated with increased testosterone. Methods: A retrospective study was performed in 51 obese female patients with BMI 30-45 kg/m2 who underwent LSG from Shanghai Tenth People’s Hospital, 38 of whom were PCOS patients. The anthropometric indexes, sex hormone and ovarian volume of ultrasound examinations include both sides ovarian volume, mean ovarian volume (MOV) and maximal ovarian volume (MaxOV) were observed preoperative and follow-up at 3 and 6 months after LSG. The metabolic indexes and ovarian volume were compared before and after surgery. Results: Compared with preoperative, PCOS patients' weight, BMI, waist circumference and hip circumference were significantly lower at 3 and 6 months after operation (P&amp;lt;0.05). Percentage of excess body weight loss(%EWL) for 3 months and 6 months after LSG was 56.32% and 75.98%. TT and cFT showed a downward trend at 3 and 6 months after surgery while SHBG showed an upward trend (P&amp;lt;0.05). Both sides ovary volume and MOV, MaxOV all decreased at 6 months after LSG, but there was no statistically significant difference compared to baseline. Compared with patients without PCOS, the preoperative MOV, MaxOV, and left ovary volume were significantly larger (P&amp;lt;0.05). At 6 months after surgery, the MOV, MaxOV, left ovary volume and right ovarian volume of PCOS and non-PCOS patients were all reduced. The differences in MOV, MaxOV, left ovary volume and right ovarian volume were no longer statistically significant between the two groups. Conclusions: TT and cFT decreased and SHBG increased significantly after LSG. MOV shrinked at 6 months after LSG and was no longer different from non-PCOS patients. LSG is not only an important treatment for weight loss, but also improve PCOS and its clinical symptoms effectively in severe obese women. Disclosure J. Gao: None. M. Zhang: None. C. Zhu: None. X. Wang: None. F. Mei: None. S. Qu: None. Funding National Natural Science Foundation of China (81601269)

The role of androgen in autophagy of granulosa cells from PCOS

Hyperandrogenism is one of the most common causes for anovulation in women and increases the risk for metabolic disorder in PCOS patients. Autophagy plays an important role in dysfunction of endocrine and anovulation. However, the relationship between hyperandrogenism and autophagy in human granulosa cells of PCOS patients remains unclear. By collecting granulosa cells from PCOS patients and non-PCOS patients, we found that the abundance of autophagy-related genes ATG5, ATG7, BECN1 mRNA and the ratio of autophagy marker protein light chain 3B II/I (LC3 II/I) were significantly increased whereas the abundance of the autophagy substrate SQSTM1/p62 was decreased in ovarian granulosa cells from PCOS patients. Furthermore, we demonstrated that BECN1 mRNA abundance in human granulosa cells positively correlated with the basal level of serum total testosterone and androgen up-regulated the abundance of BECN1 mRNA and the ratio of LC3II/LC3I in a dose-dependent manner in cultured granulosa cells. These observations indicated that androgen-induced activation of autophagy may play an important role in the development of PCOS and to explore the autophagy mechanisms involved in PCOS yield new insight into the pathophysiology and therapy of the disorder.

Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome

To determine aberrant circular RNA (circRNA) expression profiles in cumulus cells from polycystic ovarian syndrome (PCOS) patients and identify their potential biological functions. Circular RNAs microarray analysis of human tissue. University hospital. A total of 40 women, including 20 PCOS patients and 20 non-PCOS patients. None. A circRNA microarray containing probes that interrogate 21,442 human circRNAs to investigate differentially expressed circRNAs in cumulus cells, with potential target genes of significantly changed circRNAs and biological functions measured by microRNA support vector regression (mirSVR) and gene ontology (GO) analysis, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A total of 1,032 circRNAs were identified that were differentially expressed in PCOS cumulus cells, including 311 circRNAs increase and 721 circRNAs decrease (fold change ≥2). Four aberrantly expressed circRNAs reached a statistically significant result after Bonferroni correction (with Bonferroni correction, only circRNAs for which P < .05/21,442 = 2.3 × 10-6 were considered statistically significant). Further analysis showed that aberrantly expressed circRNAs harbored microRNA binding sites, and some microRNAs were associated with PCOS. The GO and KEGG biological pathway analysis indicated that the genes with protein binding, mitotic nuclear envelope disassembly and metabolic pathways were statistically significantly enriched. Our data suggest that the aberrantly expressed circRNAs and their targeted genes might be associated with PCOS, providing new clues to find key diagnostic and therapeutic molecular biomarkers for PCOS patients.

Role of Cystic Fluid Growth Factors and Inflammatory Mediators in Pathogenesis of Polycystic Ovary Syndrome

Objective: Present study was carried out to investigate whether there is any localized growth factor/s involved and mediated by inflammatory cytokines through measuring their level in fluid aspirated from ovarian cyst. Study Design: Data was collected from 62 infertile female patients having PCOS and without PCOS. The cystic and follicular fluid obtained from consented patients was used in estimating inflammatory and growth factors. Further, these values were analyzed and interpreted with respect to number, size, length and depth of cysts. Results: Indicates that there is a low level of inflammatory reaction centralized to IL-18 triggering the release of MMP-2 to degrade the extracellular matrix followed by release of ANG-1, VEGF, IGF-1 and EGF to maintain the growth of ovarian cysts. Our findings support the prominent role of IL-18, MMP-2 and ANG-1 in pathogenesis of severe PCOS. Conclusion: In conclusion, the levels of inflammatory mediators in follicular fluid are significantly higher in women having PCOS than compared to cystic fluid of Non-PCOS patients. Despite the promising results of present study we recommend the readers to consider these results as preliminary. Further larger cohort studies are recommended by including more number of heterogeneous population, for extended period of time and more number of cytokines and growth factors with higher accuracy to understand how local inflammatory and growth factors are inter-related in development of ovarian cysts in PCOS patients.

Differential Expression Patterns of Glycolytic Enzymes and Mitochondria-Dependent Apoptosis in PCOS Patients with Endometrial Hyperplasia, an Early Hallmark of Endometrial Cancer, In Vivo and the Impact of Metformin In Vitro.

The underlying mechanisms of polycystic ovarian syndrome (PCOS)-induced endometrial dysfunction are not fully understood, and although accumulating evidence shows that the use of metformin has beneficial effects in PCOS patients, the precise regulatory mechanisms of metformin on endometrial function under PCOS conditions have only been partially explored. To address these clinical challenges, this study aimed to assess the protein expression patterns of glycolytic enzymes, estrogen receptor (ER), and androgen receptor (AR) along with differences in mitochondria-dependent apoptosis in PCOS patients with and without endometrial hyperplasia in vivo and to investigate the effects of metformin in PCOS patients with endometrial hyperplasia in vitro. Here, we showed that compared to non-PCOS patients and PCOS patients without hyperplasia, the endometria from PCOS patients with hyperplasia had a distinct protein expression pattern of glycolytic enzymes, including pyruvate kinase isozyme M2 isoform (PKM2) and pyruvate dehydrogenase (PDH), and mitochondrial transcription factor A (TFAM). In PCOS patients with endometrial hyperplasia, increased glandular epithelial cell secretion and infiltrated stromal cells in the glands were associated with decreased PDH immunoreactivity in the epithelial cells. Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls. Although there was no change in PDH expression, metformin treatment increased the expression of TFAM and cleaved caspase-3. Moreover, our in vivo study showed that while endometrial ERβ expression was no different between non-PCOS and PCOS patients regardless of whether or not hyperplasia was present, ERα and AR protein expression was gradually increased in women with PCOS following the onset of endometrial hyperplasia. Our in vitro study showed that treatment with metformin inhibited ERα expression without affecting ERβ expression. Our findings suggest that decreased glycolysis and increased mitochondrial activity might contribute to the onset of ERα-dependent endometrial hyperplasia and that metformin might directly reverse impaired glycolysis and normalize mitochondrial function in PCOS patients with endometrial hyperplasia.

LncRNA BANCR participates in polycystic ovary syndrome by promoting cell apoptosis.

The long non-coding RNA (lncRNA) BANCR is a well-studied lncRNA that serves pivotal roles in various malignancies; however, to the best of our knowledge, its involvement in polycystic ovary syndrome (PCOS) remains unknown. In the present study, the expression levels of lncRNA BANCR were detected in granulosa cells (GCs) from patients with PCOS and non-PCOS patients undergoing in vitro fertilization by reverse transcription-quantitative polymerase chain reaction. Subsequently, GCs and the KGN human granulosa-like tumor cell line were treated with insulin, and BANCR expression was detected. KGN cells were also transfected with a BANCR expression vector, after which, cell proliferation, apoptosis and the expression levels of pro-apoptotic B-cell lymphoma 2-associated X protein (Bax) and p53 were detected by Cell Counting kit-8 assay, MTT assay and western blotting, respectively. The results revealed that the expression levels of lncRNA BANCR in GCs were significantly higher in patients with PCOS compared with in non-PCOS patients. In addition, insulin treatment significantly upregulated the expression of BANCR in GCs and KGN cells. Transfection with the BANCR expression vector significantly inhibited proliferation and promoted apoptosis of KGN cells, and significantly promoted the expression levels of pro-apoptotic Bax and p53. Therefore, it may be concluded that lncRNA BANCR participates in PCOS by promoting cell apoptosis through the upregulation of Bax and p53.

A Meta-Analysis of Oocyte Quality and Clinical Outcome of Intracytoplasmic Sperm Injection Cycles in Patients with Polycystic Ovary Syndrome

Whether treatment outcomes in intracytoplasmic sperm injection (ICSI) cycles differ between polycystic ovary syndrome (PCOS) and non-PCOS patients remains inconclusive. The aim of this meta-analysis is to compare oocyte quality and clinical outcomes in PCOS patients and non-PCOS patients undergoing ICSI procedure. Methods: Databases including Medline, Embase and the Cochrane Library were searched for studies published up to 18 January 2018. All articles searched were independently reviewed and selected by two evaluators according to predetermined inclusion and exclusion criteria. Results: Eight studies were selected for inclusion, and a total of 474 PCOS patients (627 cycles) were compared to age-matched controls (962 patients, 992 cycles). The total gonadotropin usage was significant less in PCOS group, and the MD was –481.72 IU [95% CI:– 603.76–359.68, P &lt; 0.00001]. A significantly higher mean number of oocytes, metaphase II (MII) oocytes and 2-pronucleated (2PN) oocytes per cycle were observed in the PCOS group than in the non-PCOS group (P &lt; 0.005), the total MDs were 4.20 [95% CI: 2.50–5.90], 1.52 [95% CI: 0.84–2.20] and 1.71 [95% CI: 0.73–2.69], respectively. The fertilization rate was comparable. The clinical pregnancy rate per transfer cycle was higher in the PCOS group, the odd ratio (OR) was 1.59 [95% CI: 1.23–2.05, P &lt; 0.005] and the live birth rate was comparable. A higher miscarriage rate was observed in the PCOS group, but this did not reach statistical significance. The risk of ovarian hyperstimulation syndrome (OHSS) was significantly higher in the PCOS group [OR: 3.01, 95% CI: 1.16–7.82, P &lt; 0.05]. Conclusions: This meta-analysis demonstrated that PCOS patients may have more favourable ICSI outcomes than non-PCOS patients. Our findings should be evaluated in further prospective cohort studies.