Outcomes In Polycystic Ovary Syndrome Research Articles

Quantitative proteomics reveals pregnancy prognosis signature of polycystic ovary syndrome women based on machine learning.

We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods. We obtained the endometrial samples from 33 PCOS patients and 7 healthy controls at the Reproductive Center of the Second Hospital of Lanzhou University from September 2019 to September 2020. Liquid chromatography tandem mass spectrometry (LCMS/MS) was conducted to identify the differentially expressed proteins (DEPs) of the two groups. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the related pathways and functions of the DEPs. Then, we used machine learning methods to screen the feature proteins. Multivariate Cox regression analysis was also conducted to establish the prognostic models. The performance of the prognostic model was then evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). In addition, the Bootstrap method was conducted to verify the generalization ability of the model. Finally, linear correlation analysis was performed to figure out the correlation between the feature proteins and clinical data. Four hundred and fifty DEPs in PCOS and controls were screened out, and we obtained some pathways and functions. A prognostic model for the pregnancy loss of PCOS was established, which has good discrimination and generalization ability based on two feature proteins (TIA1, COL5A1). Strong correlation between clinical data and proteins were identified to predict the reproductive outcome in PCOS. The model based on the TIA1 and COL5A1 protein could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a good theoretical foundation for subsequent research.

Association of Plasma Metal Levels with Outcomes of Assisted Reproduction in Polycystic Ovary Syndrome.

The objective of this study is to explore the correlation of metal levels with assisted reproductive technology (ART) outcomes in polycystic ovary syndrome (PCOS) patients. The individuals were recruited who met the research criteria, only tubal factor or male infertility served as the control group (n = 40) and patient group was PCOS patients (n = 35). Individuals (n = 75) were divided into PCOS group (n = 35) and control group (n = 40). The normal body mass index (BMI) group (control) includes women with BMI < 25kg/m2 in PCOS group (n = 24) and control group (n = 33), and BMI ≥ 25kg/m2 in PCOS group (n = 11) and control group (n = 7). We performed an analysis of insulin resistance (IR) (n = 15) group and without insulin resistance (NIR) group (n = 20) in PCOS patient and control patients. Comparing difference demographic data, ART outcomes and the metal levels in every group respectively, the correlation of metal levels and ART outcomes in control participants and PCOS patients were analyzed by the Spearman correlation analysis, and multiple linear regression model was used to examine the association between the concentration of 19 metals and ART outcomes in PCOS group and control group. Plasma manganese (Mn), titanium (Ti), sodium (Na), magnesium (Mg), copper (Cu), calcium (Ca)/Mg ratio, and Cu/zinc (Zn) ratio levels in PCOS patients were higher than that in control, while Zn and Ca levels were lower in PCOS patients than that in control. The Mg levels had a positive connection with the number of eggs recovered, and the iron (Fe) levels were positively associated with the number of transplanted embryos in PCOS-IR. In PCOS-NIR, Mn levels positively correlated with the number of follicles and the number of good embryos. Silver (Ag) levels were negatively correlated with the number of follicles, and aluminum (Al) levels were negatively related with the normal fertilization and the number of good embryos. The Spearman analysis in PCOS-BMI ≥ 25 group exhibited that nickel (Ni) levels were negatively associated with the number of follicles. The plasma metal levels seem to affect the clinical manifestations and in vitro fertilization outcomes in assisted reproduction.

Anti-obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 international evidence-based guideline.

This systematic review and meta-analysis evaluated the efficacy of anti-obesity agents for hormonal, reproductive, metabolic, and psychological outcomes in polycystic ovary syndrome (PCOS) to inform the 2023 update of the International Evidence-based Guideline on PCOS. We searched Medline, EMBASE, PsycInfo, and CINAHL until July 2022 with a 10-year limit to focus on newer agents. Eleven trials (545 and 451 participants in intervention and control arms respectively, 12 comparisons) were included. On descriptive analyses, most agents improved anthropometric outcomes; liraglutide, semaglutide and orlistat appeared superior to placebo for anthropometric outcomes. Meta-analyses were possible for two comparisons (exenatide vs. metformin and orlistat + combined oral contraceptive pill [COCP] vs. COCP alone). On meta-analysis, no differences were identified between exenatide versus metformin for anthropometric, biochemical hyperandrogenism, and metabolic outcomes, other than lower fasting blood glucose more with metformin than exenatide (MD: 0.10mmol/L, CI 0.02-0.17, I2= 18%, 2 trials). Orlistat + COCP did not improve metabolic outcomes compared with COCP alone (fasting insulin MD: -8.65 pmol/L, -33.55 to 16.26, I2= 67%, 2 trials). Published data examining the effects of anti-obesity agents in women with PCOS are very limited. The role of these agents in PCOS should be a high priority for future research.

The effect of laparoscopic ovarian drilling on pregnancy outcomes in polycystic ovary syndrome women with more than 2 in-vitro fertilization cycle failures: A pilot RCT.

Background: The effect of laparoscopic ovarian drilling (LOD) before in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles on pregnancy outcomes is an unclear and challenging subject. Objective: To evaluate the impact of LOD before IVF/ICSI cycles on controlled ovarian stimulation and pregnancy outcomes in polycystic ovary syndrome (PCOS) women with a history of more than 2 IVF failures. Materials and Methods: In this randomized clinical trial, women with PCOS diagnosis who referred to Arash Women's hospital, Tehran, Iran for IVF/ICSI cycle from August 2015-January 2018 were evaluated. Eligible participants were allocated into 2 groups randomly (n = 17/each group). The participants in the LOD group (intervention) were treated with laparoscopic couture, and after one month, they underwent IVF/ICSI cycles using the gonadotropin-releasing hormone antagonist protocol. The control group had no intervention. The oocyte and embryo qualities, ovarian hyperstimulation syndrome rate, the rates of chemical and clinical pregnancy and early miscarriage, live birth, and pregnancy complications, were compared between groups. Results: Finally, 34 participants were evaluated. The controlled ovarian stimulation outcomes were similar between groups. The ovarian hyperstimulation syndrome rate in the LOD group was significantly lower than in the control group (p = 0.04). One case of spontaneous pregnancy was reported in the LOD group. No significant difference was observed between groups in clinical pregnancy, miscarriage, and live birth rates. The rates of pregnancy complications (gestational diabetes mellitus, preeclampsia, and preterm birth) were similar between groups. Conclusion: Performing LOD before IVF/ICSI cycles did not improve the pregnancy outcomes in PCOS women, a clinical trial with a larger sample size is needed to prove these results.

The association between systemic immune-inflammation index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study

BackgroundAs a novel prognostic and inflammatory marker, the systemic immune-inflammation index (SII) has come to the foreground in recent years. SII may be used as an indicator reflecting the progressive inflammatory process in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the correlation between SII and assisted reproductive outcomes in PCOS patients.ResultsA total of 966 women undergoing in vitro fertilization (IVF) procedure with PCOS were included in the study. The SII was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). Participants were divided into four groups according to SII quartiles calculated at baseline, and the differences of clinical and laboratory outcomes between these four groups were compared. Moreover, a univariate linear regression model was used to evaluate the associations between SII and the outcomes. Patients in the highest SII quartile (Q4) had lower antral follicle count (AFC), estradiol (E2), and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) start compared with the lower three SII quartiles (Q1-Q3). Moreover, our analysis demonstrated that women in the lower SII quartiles had a higher rate of available embryos and blastocyst formation compared with those in the highest SII quartile. Logarithm of SII correlated negatively with available embryo rate, but not with number of available embryos. Additionally, the results of our multivariate logistic regression analyses indicated that the highest SII quartile was negatively associated with biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). A non-linear relationship between the SII and number of available embryos, with a negative relationship seen to the right of the inflection point was also found.ConclusionsThe interplay among thrombocytosis, inflammation, and immunity could influence assisted reproductive outcomes in PCOS patients. In this regard, SII may serve as a valuable marker for exploring potential correlations.

FRI409 Childbirth Experiences In Women With Polycystic Ovary Syndrome

Abstract Disclosure: A.E. Husby: None. M.R. Simpson: None. R. Dalbye: None. E. Vanky: None. T.S. Løvvik: None. Introduction:Polycystic ovary syndrome (PCOS) affects 5-20% of women. Women with PCOS frequently suffer from metabolic, psychological, and reproductive comorbidities. Pregnancy complications such as gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, and preterm birth are more common in PCOS. Metformin has been used in an attempt to improve pregnancy outcomes in PCOS. Childbirth experience is influenced by previous life- and birth experiences, preparedness, fear of childbirth, experiences of pain and control, and the mode and outcome of delivery. A positive childbirth experience may result in improved post-partum functioning and bonding with the newborn. In contrast, a negative childbirth experience is associated with postnatal depression, post-traumatic stress symptoms and difficulties in relating to one’s partner and newborn. To our knowledge, there are no previous studies on women with PCOS and their childbirth experiences. The primary aim of our study is to explore childbirth experiences in women with PCOS compared to a reference population. The secondary aim is to explore whether metformin vs placebo during pregnancy affects the childbirth experiences in women with PCOS. Materials and methods:This study combines data from two RCTs. In the PregMet2 study, women with PCOS in Norway, Sweden and Iceland were randomized to metformin or placebo. Main outcomes were miscarriage and preterm delivery. The Labor Progression Study (LaPS) (reference population) in Norway, compared WHO partograph to the Zhang’s guidelines for progression of labor in women in Robson group 1*. Both studies used the Childbirth Experience Questionaire (CEQ). Total CEQ scores and scores (separately) from the four domains “own capacity”, “perceived safety”, “professional support” and “participation” were compared between a) women with PCOS in the PregMet2 study (n=131) and the reference population, the LaPS study (n=3604) and b) metformin (n=179) and placebo (n=185) groups in the PregMet2 study. Results: There was no difference in total CEQ score between women with PCOS and the reference population. Women with PCOS had a higher domain score for “perceived safety” (p&amp;lt;0,05) and lower score for “own capacity” (p&amp;lt;0,05), compared to the reference population, while there was no difference in the domains “professional support” or “participation”. Total CEQ-score and domain-scores were similar for the metformin compared to placebo groups in the PregMet2 study. Conclusion: Women with PCOS compared to women in the reference population had similar childbirth experiences. However, they reported higher “perceived safety” and lower “own capacity” compared to reference women. Metformin treatment in pregnancy did not influence childbirth experience in women with PCOS. *Nulliparous women with a singleton, term pregnancy, with spontaneous start of labor and cephalic lie (Robson group 1). Presentation: Friday, June 16, 2023

SAT387 Impact Of Genetic Background On Chronic Inflammation In A Letrozole-induced Mouse Model Of PCOS

Abstract Disclosure: N. Ujagar: None. G. De Robles: None. L. Velez: None. M. Seldin: None. D. Nicholas: None. The etiology behind polycystic ovary syndrome (PCOS) is elusive due to the heterogeneity of its symptoms and varying severity in patients. There are a wide variety of factors associated with PCOS, like hyperinsulinemia, hyperandrogenism, endotoxemia and chronic inflammation that have been implicated as causal factors in the condition. However mechanisms of cause and effect are difficult to establish in human cohorts. Endotoxemia, observed in humans and mouse models of PCOS, is known to trigger chronic inflammation by activating immune cells. Although correlation of chronic inflammation with PCOS has been established, the type of inflammation in PCOS patients has not been defined, in part due to the genetic variance from person to person. Using a systems immunology approach to mimic human genetic diversity, combined with a letrozole-induced PCOS mouse model, we aim to distinguish the types of inflammation present in PCOS. We analyzed the immune cells from lymph nodes and spleens of 21 different strains of PCOS induced and control mice (130 mice in total), and found that based on genetic background the reproductive and metabolic phenotypes differed- similar to how PCOS presents clinically. Splenocytes from these control and PCOS mice were activated in vitro to trigger T cell and myeloid cell cytokine secretion, which was measured via luminex. Clustering analysis of these multi-analyte cytokine measurements together with flow cytometry of the immune cells allowed us to identify T-helper 17 (Th17) cells as the prominent immune cell driving inflammation in letrozole-induce mouse model of PCOS independent of genetic background. This systems immunology approach has allowed us to define PCOS associated inflammation and will be the basis for integrating human inflammation in PCOS with mouse models that appropriately recapitulate disease. The discovery of Th17 cells as key inflammatory mediators provide targets for understanding the mechanisms linking chronic inflammation to reproductive and metabolic outcomes in PCOS, and will assist in future development of anti-inflammatory therapies. Presentation Date: Saturday, June 17, 2023

LH on GnRH-ant day to basal LH affects the IVF/ICSI outcome of PCOS women undergoing GnRH-antagonist protocol.

The aim of this study was to investigate the influence of ratio of serum luteinizing hormone (LH) on gonadotropin-releasing hormone antagonist (GnRH-ant) day to basal LH (hLH/bLH) on in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) outcome in polycystic ovary syndrome (PCOS) women who received GnRH-ant protocol for controlled ovarian hyperstimulation (COH). This retrospective study was conducted in women with PCOS (n = 1116) who underwent the GnRH-ant protocol for COH between 2015 and 2022 and were stratified as group A (hLH/bLH < 1, n = 489) and group B (hLH/bLH ≥ 1, n = 627) according to the variation of serum LH. The outcomes of COH and the first frozen embryo transfer (FET) cycle were compared between group A, B and the linear relationship between hLH/bLH ratio and IVF/ICSI outcomes were studied by multivariate linear regression analysis and restricted cubic spline (RCS) models. There were significant differences in baseline characteristics and outcomes between group A and B. Group A had higher levels of bLH, AMH, estradiol (E2) on GnRH-ant start day and lower levels of LH on GnRH-ant start day. Group B has better ovulation induction outcomes: more retrieved oocytes, normally fertilized oocytes (2PN), cleavage embryos, available embryos and high-quality blastocysts. Multivariate linear regression analysis found no statistically significant connection between hLH/bLH and clinical outcomes. RCS models showed hLH/bLH had nonlinear association with outcomes, including number of oocytes retrieved, 2PN, available embryos, incidence of OHSS, chemical pregnancy, clinical pregnancy, abortion and live birth. hLH/bLH ratio could be a more forward-looking indicator of clinical outcome in women with PCOS undergoing GnRH-ant protocols than LH on trigger day and the ratio of LH level on trigger day to basal LH. hLH/bLH = 1 may be the best condition for higher live birth rate and lower OHSS rate.

Effect of basal luteinizing hormone (bLH) level on in vitro fertilization/intra-cytoplasmic injections (IVF/ICSI) outcomes in polycystic ovarian syndrome (PCOS) patients

ObjectiveTo evaluate the effect of basal luteinizing hormone (bLH) levels on In Vitro Fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) outcomes in polycystic ovary syndrome (PCOS).MethodsA total of 256 PCOS patients who underwent IVF/ICSI treatment in our center from January 2018 to January 2022 were analyzed retrospectively. The patients were based on the third quartile (12.455) of the basal LH value was taken as the cut-off value and was divided into high and low LH group: high LH group (LH ≥ 12.455 IU / L) and low LH group (LH < 12.455 IU / L) and the OC group was pretreated with oral contraceptives. The outcomes in ovulation induction and embryo transfer cycles of the three groups were then compared. In addition, factors influencing the number of good quality embryos and the early onset LH peak were analyzed.ResultsAges, infertility duration, body mass index (BMI), and basal follicle-stimulating hormone (FSH), and progesterone (P), testosterone (T) levels were not significantly different among the three groups (p > 0.05). However,there were significant differences in basal LH and basal E2 between low LH group and high LH group, and there were significant differences in basal LH between high LH group and OC group (p < 0.05). LH on the antagonist day was significantly different between low LH group and high LH group and between high LH group and OC group (p < 0.05). LH on the hCG (human Chorionic Gonadotropin) day there were significant differences between low LH group and OC group, high LH group and OC group (p < 0.05). The Mode of triggering between the three groups had significant differences between the two groups (p < 0.05). In addition, the number of days from gonadotropin (Gn) initiation to antagonist addition were significantly different among the three groups (p < 0.05). In addition, total Gn doses,the number of oocytes retrieved, the number of Gn days, 2pronucleus (2PN) numbers, number of good quality embryos, and number of high risk OHSS (Ovarian Hyper-stimulation Syndrome), cases with OHSS occurrences were not significantly different among the three groups (p > 0.05). Moreover, the cycle and clinical pregnancy outcomes and the cumulative clinical pregnancy rate and the cumulative live birth rate were not significantly different among the three groups (p > 0.05). LH levels on the day of antagonist addition affected the number of good-quality embryos (B < 0, p < 0.05). However, LH levels on the day antagonist was added were not significantly correlated with basal LH levels (Pearson correlation coefficient = 0.259), the ROC curve was constructed for the logistic prediction model of the early onset LH peak, and the AUC value was 0.747, indicating that the logistic combined model we constructed had a good ability to predict the early onset LH peak.ConclusionBasal LH levels do not affect the pregnancy outcomes in PCOS patients after antagonist protocols. Besides, LH levels on the day of antagonist addition affect the number of good quality embryos for PCOS patients undergoing IVF /ICSI.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

Leptin Inhibition Ameliorates Renal Mitochondrial Dysfunction And Associated Renal Injury In Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and polycystic ovaries. Renal injury, increased central adiposity and higher circulating levels of the adipokine leptin are common characteristics of PCOS. Leptin has direct renal fibrotic, hypertrophic, and albuminuric effects and can cause renal mitochondrial dysfunction and oxidative stress leading to chronic kidney disease development. Despite increased circulating leptin level in both lean and obese PCOS women, its role in PCOS-mediated renal damage remains unknown. In a well-characterized mouse model of PCOS, we aimed to test the hypothesis that hyperandrogenemia increases central adiposity leading to hyperleptinemia, which via leptin receptors induces intrarenal mitochondrial oxidative stress and dysfunction causing renal injury. Methods: Three-week-old peripubertal female mice were implanted with Silastic tubes filled with the non-aromatizable androgen dihydrotestosterone (DHT, 8 mg) or vehicle for 12 weeks. Eight weeks post-Silastic tubes implantation, the animals were treated with the leptin receptor antagonist (LepR-Ant) pegylated leptin (2 mg/kg, ip, 3x/week) for 4 weeks. Body weight, fat mass (EchoMRI), kidney weight (gravimetry), plasma leptin (ELISA), the glomerular filtration rate (GFR, transcutaneous fluorescence), as well as the renal injury markers urinary albumin to creatinine ratio (UACR, clinical chemistry analyzer), NGAL, and KIM1 (ELISA) were measured. Freshly isolated kidney mitochondria were used to measure mitochondrial reactive oxygen species (mtROS) by Amplex Red assay. Moreover, mitochondrial complex I and complex II-driven respiration and complex IV activity were assessed using Oroboros Fluorespirometer. Results: DHT significantly (p&lt;0.05) increased body weight (31.6 ± 2.3 vs. 23.6 ± 0.5 g), fat mass (3.5 ± 0.6 vs. 1.9 ± 0.4 g), kidney weight (365.6 ± 13.1 vs. 257.1 ± 3.7 mg), leptin (3.7-fold), UACR (1013.3 ± 56.4 vs. 658.9 ± 103.6 μg albumin/g creatinine), NGAL (6-fold), and KIM1 (3.7-fold). Moreover, PCOS mice had significantly (p&lt;0.05) lower GFR (1067.2 ± 59.9 vs. 1335.6 ± 60.3 uL/min/100g body weight), higher mtROS driven by complexes I (3.8 ± 0.8 vs. 2.0 ± 0.3 % electron leak) and III (8.0 ± 1.8 vs. 3.7 ± 0.9 % electron leak), as well as lower complexes I, II, and IV respiration (43-71%). The LepR-Ant had no effect on kidney weight or GFR; however, it abolished DHT-induced increases in body weight and fat mass. Excitingly, the LepR-Ant inhibited mtROS generation and completely restored complex I and II respiration, which was associated with a significant reduction in the urinary renal injury markers UACR, NGAL, and KIM-1 levels (40-60%, p&lt;0.05). Conclusion and significance: Our findings suggest that leptin via its receptor activation plays a significant role in the renal outcomes in PCOS by inducing mitochondrial dysfunction. Leptin receptor blockade could be a novel therapeutic approach to ameliorate renal injury in PCOS. Supported by NIH grants NIGMS P20GM121334 to KSE, LLYC, and DGR, NIGMS P20GM104357, NHLBI P01HL51971, and American Heart Association Predoctoral Fellowship 903804 (A.M.H.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The influence of polycystic ovary syndrome on abortion rate after in vitro fertilization/intracytoplasmic sperm injection fresh cycle pregnancy

There are many reports on clinical pregnancy outcomes in polycystic ovary syndrome (PCOS) patients receiving vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), but little research about abortion has been done and there is a debate on whether the abortion risk increases in PCOS patients receiving IVF/ICSI. Therefore, the aim of this study was to investigated the abortion in PCOS patients. Clinical data of 12055 IVF/ICSI fresh cycles performed in our hospital from January 2015 to December 2020 were collected. Based on the Rotterdam diagnostic criteria of PCOS and after propensity score matching (PSM) for baseline data of clinical pregnancy cycles, matched 599 PCOS (PCOS group) and Non-PCOS (non-PCOS group) cycles were obtained. Abortion and abortion-related outcomes were compared between the two groups. Risk factors for late abortion in twins were analyzed using binary Logistics regression. Post-PSM data showed that the late abortion rate was significantly higher in the PCOS group than in the non-PCOS group only in twin pregnancy (9.50% vs. 3.96%, OR: 2.55, 95%CI 1.10–5.89). There were no statistical differences in other pregnancy outcomes. The etiological distribution for late abortion were not statistically different between the two groups in both singletons and twins. Logistics regression indicated that PCOS and obesity [pregnancy-assisted body mass index (BMI) ≥ 28] were risk factors for late abortion in twin pregnancy. In twin pregnancy, PCOS and obese patients are more likely to have late abortion. In twin pregnancy, the late abortion risk significantly increased in the PCOS patients as compared with non-PCOS patients (OR: 2.59, 95%CI 1.11–6.03, P < 0.05), as well as in the patients with obesity (BMI ≥ 28) as compared with the patients with normal BMI (OR: 4.17, 95%CI 1.59–10.90, P < 0.05). PCOS does not significantly affect early and overall late abortion rates after IVF/ICSI fresh cycle pregnancy.

Elevated baseline LH/FSH ratio is associated with poor ovulatory response but better clinical pregnancy and live birth in Chinese women with PCOS after ovulation induction

BackgroundWhat is the association between elevated baseline LH/FSH ratio and reproductive outcomes, especially ovulatory response, among Chinese women with polycystic ovary syndrome (PCOS) after ovulation induction. MethodsThis was a secondary analysis of a multicenter randomized trial in 1000 women with PCOS from 21 sites (27 hospitals) in Mainland China. LH and FSH levels before ovulation induction and the main outcomes including ovulation, biochemical pregnancy, clinical pregnancy, miscarriage, and live birth were measured. A linear regression model, logistic regression models and Cox proportional hazard regression model were used to estimate the association between LH/FSH ratios and reproductive outcomes in PCOS. ResultsLH/FSH ratio was significantly associated with age, body mass index (BMI), total testosterone (TT), estradiol (E2), free testosterone (FT), and antimullerian hormone (AMH). Anovulatory women had significantly higher LH/FSH ratio than ovulatory women (P = 0.003), especially in women with young age (P = 0.023), high BMI (P = 0.002), low E2 (P = 0.002), FT (P = 0.010), TT (P < 0.001) and AMH(P = 0.032). Women with elevated LH/FSH ratio were associated with lower ovulation (LH/FSH≥1 OR = 0.42, 95% CI, 0.26–0.68; LH/FSH≥2 OR = 0.32, 95% CI, 0.20–0.54; LH/FSH≥3 OR = 0.40, 95% CI 0.21–0.74) when compared with LH/FSH<1. The association was held after adjustment for treatment with or without the confounding factors. Although no association between LH/FSH ratio and biochemical pregnancy, women with 1 ≤ LH/FSH<2 were associated with higher clinical pregnancy (OR = 1.71; 95% CI, 1.09–2.67) and live birth (OR = 1.73; 95% CI, 1.09–2.75) compared to women with LH/FSH<1. Women with 2 ≤ LH/FSH<3 were associated with lower miscarriage rate (OR = 0.38; 95% CI, 0.16–0.93). ConclusionsElevated baseline LH/FSH ratio in women with PCOS was associated with poor ovulatory response, but women were more likely to achieve clinical pregnancy and live birth than women with normal LH/FSH. It suggests LH and FSH in women with PCOS may play a role in successful pregnancy despite of negative impact in ovulation.

Endometrial Pathology and Reproductive Outcomes in Polycystic Ovary Syndrome (PCOS)

Introduction: The common and key in the pathogenesis of PCOS and chronic endometritis (CE) is the chronic course of inflammation. Persistent damage to the endometrium leads to impaired endometrial receptivity and creates conditions for the development of infertility. The purpose of the study was to identify the most common endometrial pathology in women with PCOS and infertility and to analyze the effectiveness of infertility treatment in women with this pathology, to evaluate reproductive outcomes. Materials and methods: Analyzed 240 case histories of patients of LLC “Clinic of Professor Pasman”, Novosibirsk Clinical Oncological Dispancery for the period 2012-2022, diagnosed with PCOS, Infertility. Patients were included in the study group by random sequential selection. The frequency of occurrence of each of the PCOS phenotypes was analyzed, as well as the prevalence of endometrial pathology. The most common pathology is chronic endometritis, therefore, in addition to the standard methods of treating infertility in PCOS, CE was additionally treated by the following methods: photodynamic therapy (PDT) and the introduction of a macrophage medium into the uterine cavity. Results and discussion: In 61% of cases, hysteroscopy was performed and endometrial pathology was detected, which indicates the need to diagnose the endometrium in women with PCOS, especially before using ART. The most common endometrial pathology is chronic endometritis (61.6%). PDT and the introduction of macrophage medium increase the effectiveness of the treatment of CE and infertility in PCOS. The results obtained indicate a high incidence of PCOS without hyperandrogenism and obesity.

Impact of baseline luteinizing hormone (LH) level and anti-Müllerian hormone (AMH) on pregnancy outcomes in polycystic ovary syndrome (PCOS) patients undergoing IVF/ICSI cycle in antagonist protocol

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder often associated with infertility. There are several factors that could impair the pregnancy outcomes of PCOS patients. The latter endocrine profile along with high baseline luteinizing hormone (LH), high LH/follicle-stimulating hormone ratio, as well as high anti-Müllerian hormone (AMH) levels appear detrimental for patients undergoing In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The objective of this study is to evaluate the impact of baseline LH and AMH levels on pregnancy outcomes in PCOS patients performing IVF/ICSI cycles in an antagonist protocol. Materials and methods: The current investigation is a retrospective cohort study conducted at IVF Tiziri Center in Algiers on PCOS patients undergoing IVF/ICSI from January 2017 to March 2021. According to the Rotterdam criteria, patients aged between 23 and 42 years were divided into 2 groups: group 1 (G1) =91 patients; group 2 (G2) =100 all patients had an LH level &gt;10 IU/L. Both groups had AMH levels &gt;5 ng/mL. Controlled ovarian stimulation was done with a fixed antagonist protocol, as for the ovulation it was triggered with human chorionic gonadotropin or gonadotropin-releasing hormone agonist. Fresh and frozen embryo transfers were, thereafter, evaluated. Concerning the statistical analysis, it was done with SPSS software. Results: The mean LH level was 15.16±7.08 for G1 versus 5.7±1.86 for G2 (P=10−6), mean LH/follicle-stimulating hormone ratio 2.71±1.36 in G1 versus 1.05±0.44 (P=10−6) and mean AMH level was 9.27±3.90 for G1 versus 7.53±2.76 for G2 with (P&lt;10−3). The mean follicles over 11 mm in diameter, estradiol (E2) level, and progesterone level on the trigger day did not differ significantly between G1 and G2. Also, the mean of oocytes and metaphase II oocytes retrieved fertilization, and blastulation rate were similar for both groups. The pregnancy rate for G1 was 40.6% versus 54% (P&gt;0.05); the ongoing pregnancy rate (OPR) was 28.6% in G1 versus 47% in G2 (P=0.078); and the miscarriage rate was 32.4% for G1 versus 12.9 for G2 (P=0.072). A univariate analysis was performed with all confounder factors supposed to impact pregnancy outcomes: AMH level did not impact pregnancy outcomes, whereas LH level &lt;11 IU/L has been determined as a threshold impacting positively on OPR with odds ratio=2.01 (95% CI: 1.05–3.87). After a multivariate logistic regression including con-founders, 3 factors significantly influence OPR: LH, E2, and infertility with known etiology. Conclusion: The high baseline LH level impairs pregnancy outcomes in PCOs patients undergoing an antagonist protocol IVF/ICSI cycle. The identification of PCOS patients by their endocrine profile enables the establishment of a prognosis for council patients and a plan for an individualized therapeutic strategy.

Effect of different timing of letrozole initiation on pregnancy outcome in polycystic ovary syndrome.

To investigate the efficacy of oral letrozole (LE) starting on day 3 or 5 of the menstrual cycle in patients with polycystic ovary syndrome (PCOS). Retrospective cohort study. Reproductive Endocrinology Department of Hangzhou Women's Hospital. In this retrospective analysis, we analyzed patients who received oral LE for ovulation induction (OI) at the Hangzhou Women's Hospital from January 2016 to January 2021. In total, 539 PCOS patients with fertility requirements were classified into the D3 group and D5 group according to the different starting times of oral LE, that is, from the 3rd or 5th day of the menstrual cycle or LE is taken orally for 5 days starting on day 3 or 5 of progesterone withdrawal bleeding. Treatment started with one tablet (LE 2.5 mg), continue the regimen from the previous cycle in non-responders and continued until pregnancy or for up to three ovulatory cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The primary outcome was to compare ovulation rates, conception rates, live birth rates, pregnancy complications, and pregnancy outcomes at different initiation times. Women who started LE on the 5th day of their menstrual cycle had more cumulative conception rates than those who started LE on the 3rd day(173 of 228[75.9%]vs. 201 of 311[64.6%], P= 0.005; rate ratio for conception, 1.174; 95% confidence interval,1.052 to 1.311) without significant differences in overall live birth rate, though there were 142 of 228[62.3%] in the D5 group versus 172 of 311[55.3%] in the D3 group (P= 0.105). The median (IQR) endometrial thickness was significantly (P = 0.013) greater during the D5 group treatment compared to the D3 group, which may be related to higher conception and clinical pregnancy rates. The median (IQR) maximum follicle diameter was not statistically (P = 0.073) different between the two groups. The cumulative ovulation per cycle rate was higher with D5 than with D3 (287 of 405 treatment cycles [70.9%] vs. 388 of 640 treatment cycles [60.6%], P=0.001). There were no significant between-group differences in pregnancy loss (31 of 173 conceptions in the D5 group [17.9%] and 29 of 201 conceptions in the D3 group [14.4%]) or multiples pregnancy (8.2% and 10.5%, respectively). Rates of other adverse events during pregnancy were similar in the two treatment groups. As compared with D3 group, D5 group was associated with higher ovulation and conception rates, shorter time-to-pregnancy among infertile women with the PCOS.

Elevated serum uric acid level is associated with adverse reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles: a retrospective cohort study

Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for invitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with invitro fertilization outcomes. The live birth rate was the main outcome. After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4:45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

Role of the JAK/STAT3 Pathway in Obesity‐Induced Renal Injury in Polycystic Ovary Syndrome

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder in reproductive‐age women, is characterized by oligo‐ or anovulation, hyperandrogenism, and polycystic ovaries. Both animal models and women with PCOS exhibit inflammation, obesity, and renal damage. The molecular mechanisms that mediate renal injury and dysfunction in PCOS, as well as its modulation by the diet are poorly understood. The JAK/STAT3 pathway, which is activated by interleukin‐6 (IL‐6) and leptin receptors, is involved in the pathophysiology of different models of renal injury. Despite its chronic activation in extra‐renal tissues in PCOS and obesity models, the role of the JAK/STAT3 pathway in PCOS‐mediated renal damage remains unknown. We aim to test the hypothesis that an obesogenic diet, via increased leptin and IL‐6, activates the JAK/STAT3 signaling pathway to exacerbate androgen‐induced renal injury.MethodsThree‐week‐old peripubertal female mice were implanted with Silastic tubes filled with the non‐aromatizable androgen dihydrotestosterone (DHT, 8 mg) or vehicle (empty tubes). Animals were fed either a high‐fat diet (HFD; 60% kcal fat) or a low‐fat diet (LFD; 10% kcal fat, sucrose‐matched) for 90 days. Fat mass (EchoMRI), serum leptin (ELISA), kidney weight (gravimetry), and urinary albumin to creatinine ratio (UACR, clinical chemistry analyzer) were measured. Markers of renal inflammation [IL‐6, tumor necrosis factor‐α (TNF‐α)], oxidative stress [NADPH oxidase2 (Nox2)], and fibrosis [collagen I, collagen III, transforming growth factor‐β (TGF‐β), and fibronectin] were quantified by RT‐qPCR. Western blot analysis of active STAT3 [phosphorylated‐STAT3 (Tyr705)] and total STAT3 proteins expression in the kidneys was also performed.ResultsIn LFD‐fed mice, DHT increased fat mass (20.28 ± 1.10 vs. 6.78 ± 0.43 g, p&lt;0.05), serum leptin (1114.13 ± 133.68 vs. 299.27± 25.32 pg/mL, p&lt;0.05), kidney weight (33.79 ± 1.35 vs. 26.52 ± 1.08 g, p&lt;0.05) and UACR (1,227 ± 420 vs. 404 ± 169 μg albumin/g creatinine, p&lt;0.05). DHT also increased the expression of renal inflammatory markers (TNF‐α and IL‐6). Notably, while DHT upregulated the expression of the fibrotic marker TGF‐β in LFD‐fed mice, it only induced the expression of Collagen I and Nox2 in the HFD‐fed mice. Furthermore, HFD exacerbated DHT‐mediated increases in adiposity and circulating leptin and IL‐6, as well as renal inflammation, hypertrophy, and UACR. The disturbance in the aforementioned parameters was associated with increased renal STAT3 phosphorylation in HFD‐fed DHT‐treated mice compared to LFD‐ or HFD‐fed controls (2.00‐ and 2.86‐fold, respectively, p&lt;0.05).Conclusion and significanceOur findings suggest that diet‐induced obesity plays a significant role in the renal outcomes in PCOS, and that increased STAT3 activation may explain the exacerbated renal injury in HFD‐fed DHT‐treated female mice. JAK/STAT3 pathway modulation could be novel therapeutic approach for diet‐induced renal injury in PCOS. The implications of inhibiting specific STAT3 pathway components on the exacerbated renal impairment caused by obesity in our model of PCOS are currently being investigated.

Effect of lncRNA MALAT1 on the Granulosa Cell Proliferation and Pregnancy Outcome in Patients With PCOS.

Follicle arrest is one of the main characteristics of polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductive-aged women. Increasing evidence proves that high anti-Mullerian hormone (AMH) levels may play an important role in follicular development. Long noncoding RNA (lncRNA) with a length of more than 200 nt is widely involved in the directional differentiation, growth, and development of cells, whereas whether lncRNA is involved in AMH’s role in follicular development is unknown. In this study, we analyzed lncRNA expression in ovarian granulosa cells (GCs) collected from women with and without PCOS via high-throughput sequencing. The results showed that a total of 79 noncoding transcripts were differently expressed in GCs of PCOS patients, including upregulated lncRNA MALAT1. The upregulation of MALAT1 was further confirmed by RT-qPCR in GCs from a larger cohort of PCOS patients. Furthermore, knockdown MALAT1 can promote the proliferation of KGN cell in vitro. These data suggested a role for MALAT1 in the development of PCOS. Meanwhile, MALAT1 and phosphorylated SMAD 1/5 (Ser463/465) protein were upregulated in KGN cells after exogenous AMH stimulation, which identified AMH perhaps as a regulator for the expression of MALAT1. We also found that MALAT1 can predict clinical pregnancy outcome to a certain extent by ROC curve analysis (area: 0.771, p = 0.007, 95% CI: 0.617–0.925, sensitivity: 57.1%, specificity: 91.7%). Thus, our findings revealed a role of lncRNA MALAT1 in inhibiting granulosa cell proliferation and may be correlated with pregnancy outcome in PCOS.