Background: PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients.
Methods: This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model.
Results: The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157-0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability.
Conclusion: The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.
{"title":"Development and validation of a prediction model for suboptimal ovarian response in polycystic ovary syndrome (PCOS) patients undergoing GnRH-antagonist protocol in IVF/ICSI cycles.","authors":"Xiaohang Xu, Yilin Jiang, Jinlin Du, Haoyue Sun, Xue Wang, Cuilian Zhang","doi":"10.1186/s13048-024-01437-w","DOIUrl":"10.1186/s13048-024-01437-w","url":null,"abstract":"<p><strong>Background: </strong>PCOS patients with unexpectedly low oocyte yield following conventional ovarian stimulation are referred to as suboptimal responders. However, identifying suboptimal responders presents a significant challenge within reproductive medicine and limited research exists on the occurrence of suboptimal response. This analysis aimed to develop a predictive model of suboptimal response during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments in PCOS patients.</p><p><strong>Methods: </strong>This retrospective study involved a cohort of 313 PCOS patients undergoing their first IVF/ICSI cycle from 2019 to 2022. Univariate logistic regression analyses, least absolute shrinkage, selection operator regression analysis, and recursive feature elimination were employed to identify relevant characteristics and construct predictive models. Moreover, a nomogram was constructed based on the best model. Receiver operating characteristic curves, decision curve analysis (DCA), and calibration curves were used to evaluate the model.</p><p><strong>Results: </strong>The predictors included in the model were age, Anti-Mullerian hormone, antral follicle count, and basal follicle-stimulating hormone. The area under the receiver operating characteristic curve (AUC) was 0.7702 (95% confidence interval 0.7157-0.8191). The AUC, along with the DCA curve and calibration curve, demonstrated a satisfactory level of congruence and discrimination ability.</p><p><strong>Conclusion: </strong>The nomogram effectively predicted the probability of suboptimal response in PCOS patients undergoing gonadotropin-releasing hormone antagonist protocol during IVF/ICSI treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.
{"title":"Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function.","authors":"Wen-Jiao Liu, Li-Shu Li, Meng-Fan Lan, Jian-Zhou Shang, Jin-Xin Zhang, Wen-Jie Xiong, Xin-Le Lai, Xing Duan","doi":"10.1186/s13048-024-01442-z","DOIUrl":"10.1186/s13048-024-01442-z","url":null,"abstract":"<p><p>Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1186/s13048-024-01415-2
Lin Lin, Guoyong Chen, Yun Liu
Background: The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied.
Methods: We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared.
Results: The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D3 quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05).
Conclusions: The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.
背景:提高拮抗剂妊娠疗效的关键是在控制性卵巢刺激(COS)周期中更好地同步卵泡生长,尤其是在卵巢储备功能减退(DOR)的患者中。在体外受精-胚胎移植(IVF-ET)治疗过程中,黄体期雌激素预处理可提高卵泡发育的同步性和成熟卵母细胞的产量。然而,雌激素预处理对基础卵泡刺激素(FSH)水平升高的 DOR 患者的影响尚未得到充分研究:我们回顾性分析了基础 FSH 水平升高和 DOR 患者(401 个周期)接受体外受精/卵胞浆内单精子显微注射(ICSI)辅助受孕的临床数据。两组患者均采用灵活的促性腺激素释放激素(GnRH)拮抗剂治疗方案,并根据是否接受黄体雌激素预处理分为两组。雌激素预处理组有 79 名患者,对照组有 322 名患者。在月经周期的第二天,开始对卵巢进行促性腺激素(Gn)刺激。对两组患者的一般特征、临床、生物学参数和结果进行了比较:结果:两组患者的基本情况相似(P>0.05)。预处理组中更多患者在促性腺激素(Gn)启动后出现 FSH 反弹,导致 Gn 天数和总 Gn 显著高于对照组(P 3),两组之间的胚胎质量、囊胚形成率、新鲜胚胎临床妊娠率、累积妊娠率和不可移植胚胎率差异较大(P > 0.05):基础FSH升高合并DOR的患者使用黄体期雌激素预处理会导致负反馈释放后FSH水平升高,不利于早期卵泡生长,不能提高卵泡产出率,可能会增加控制性促排卵药物的使用和持续时间,也不能增加获卵数或改善临床结局。
{"title":"Value of estrogen pretreatment in patients with diminished ovarian reserve and elevated FSH on a line antagonist regimen: a retrospective controlled study.","authors":"Lin Lin, Guoyong Chen, Yun Liu","doi":"10.1186/s13048-024-01415-2","DOIUrl":"10.1186/s13048-024-01415-2","url":null,"abstract":"<p><strong>Background: </strong>The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared.</p><p><strong>Results: </strong>The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P < 0.05). There was no statistically significant difference in the number of days of antagonist use, follicle output rate (FORT), number of metaphase II(MII)eggs obtained, number of Two pronuclei (2PN) fertilized, number of D<sub>3</sub> quality embryos, blastocyst formation rate, fresh embryo clinical pregnancy rate, cumulative pregnancy rate, and non-transferable embryo rate between the two groups (P > 0.05).</p><p><strong>Conclusions: </strong>The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term “small extracellular vesicles (sEVs)” that includes exosomes for particles that are 30–200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term “exosomes”. Therefore, this review will use the term “exosomes” interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.
{"title":"Exosomes in diagnostic and therapeutic applications of ovarian cancer","authors":"Dhaval Bhavsar, Rajeswari Raguraman, Dongin Kim, Xiaoyu Ren, Anupama Munshi, Kathleen Moore, Vassilios Sikavitsas, Rajagopal Ramesh","doi":"10.1186/s13048-024-01417-0","DOIUrl":"https://doi.org/10.1186/s13048-024-01417-0","url":null,"abstract":"Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term “small extracellular vesicles (sEVs)” that includes exosomes for particles that are 30–200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term “exosomes”. Therefore, this review will use the term “exosomes” interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141150112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1186/s13048-024-01438-9
Lu Chen, Wujiang Gao, Li Lin, Chunli Sha, Taoqiong Li, Qi Chen, Hong Wei, Meiling Yang, Jie Xing, Mengxue Zhang, Shijie Zhao, Wenlin Xu, Yuefeng Li, Lulu Long, Xiaolan Zhu
{"title":"Correction: A methylation‑ and immune‑related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance.","authors":"Lu Chen, Wujiang Gao, Li Lin, Chunli Sha, Taoqiong Li, Qi Chen, Hong Wei, Meiling Yang, Jie Xing, Mengxue Zhang, Shijie Zhao, Wenlin Xu, Yuefeng Li, Lulu Long, Xiaolan Zhu","doi":"10.1186/s13048-024-01438-9","DOIUrl":"10.1186/s13048-024-01438-9","url":null,"abstract":"","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis.
Results: Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples.
Conclusion: A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy.
{"title":"Analysis of prognostic value of lactate metabolism-related genes in ovarian cancer based on bioinformatics.","authors":"Jinrui Sun, Qinmei Feng, Yingying Xu, Ping Liu, Yumei Wu","doi":"10.1186/s13048-024-01426-z","DOIUrl":"10.1186/s13048-024-01426-z","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis.</p><p><strong>Results: </strong>Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples.</p><p><strong>Conclusion: </strong>A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: This clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory factors, and anti-Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS).
Method: This study was a randomized clinical trial, double-blinded, placebo-controlled that was carried out on 90 women with PCOS. Patients were divided into two groups: receiving an OEA supplement (n = 45) or a placebo (n = 45). The intervention group received 125 mg/day OEA and the placebo group received the wheat flour for 8 weeks. Demographic data were collected through questionnaires. Fasting blood sugar (FBS), insulin resistance (IR), total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and AMH were measured before and after the study.
Results: Data analysis of food recall and physical activity questionnaires, showed no significant differences between the two groups (p > 0.05). Biochemical factors including glycemic status, MDA, inflammatory factors, and AMH decreased significantly (p < 0.05). TAC increased remarkably (p < 0.05) in comparison between the two groups, after the intervention.
Conclusion: OEA supplement with anti-inflammatory characteristics could be efficient independent of diet changes and physical activity in improving disrupted biochemical factors, so both supplementation or food resources of this fatty acid could be considered as a compensatory remedy in patients with PCOS.
Trial registration: This study was retrospectively (09-01-2022) registered in the Iranian website ( www.irct.ir ) for registration of clinical trials (IRCT20141025019669N20).
{"title":"Examining the oleoylethanolamide supplement effects on glycemic status, oxidative stress, inflammation, and anti-mullerian hormone in polycystic ovary syndrome.","authors":"Fatemeh Taghizadeh Shivyari, Hamideh Pakniat, Mohamadreza Rashidi Nooshabadi, Shaghayegh Rostami, Hossein Khadem Haghighian, Mohammad Reza Shiri-Shahsavari","doi":"10.1186/s13048-024-01432-1","DOIUrl":"10.1186/s13048-024-01432-1","url":null,"abstract":"<p><strong>Objective: </strong>This clinical trial was designed and conducted due to the anti-inflammatory potential of Oleoylethanolamide (OEA) to examine the effect of OEA supplement on glycemic status, oxidative stress, inflammatory factors, and anti-Mullerian hormone (AMH) in women with polycystic ovary syndrome (PCOS).</p><p><strong>Method: </strong>This study was a randomized clinical trial, double-blinded, placebo-controlled that was carried out on 90 women with PCOS. Patients were divided into two groups: receiving an OEA supplement (n = 45) or a placebo (n = 45). The intervention group received 125 mg/day OEA and the placebo group received the wheat flour for 8 weeks. Demographic data were collected through questionnaires. Fasting blood sugar (FBS), insulin resistance (IR), total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and AMH were measured before and after the study.</p><p><strong>Results: </strong>Data analysis of food recall and physical activity questionnaires, showed no significant differences between the two groups (p > 0.05). Biochemical factors including glycemic status, MDA, inflammatory factors, and AMH decreased significantly (p < 0.05). TAC increased remarkably (p < 0.05) in comparison between the two groups, after the intervention.</p><p><strong>Conclusion: </strong>OEA supplement with anti-inflammatory characteristics could be efficient independent of diet changes and physical activity in improving disrupted biochemical factors, so both supplementation or food resources of this fatty acid could be considered as a compensatory remedy in patients with PCOS.</p><p><strong>Trial registration: </strong>This study was retrospectively (09-01-2022) registered in the Iranian website ( www.irct.ir ) for registration of clinical trials (IRCT20141025019669N20).</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-18DOI: 10.1186/s13048-024-01434-z
Hui Chen, Ping Nie, Jingling Li, Yongqi Wu, Bo Yao, Yabing Yang, Gendie E Lash, Ping Li
Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.
{"title":"Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction.","authors":"Hui Chen, Ping Nie, Jingling Li, Yongqi Wu, Bo Yao, Yabing Yang, Gendie E Lash, Ping Li","doi":"10.1186/s13048-024-01434-z","DOIUrl":"10.1186/s13048-024-01434-z","url":null,"abstract":"<p><p>Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR).
Methods: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions.
Results: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect.
Conclusion: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline.
Trial registration: Retrospectively registered.
背景:碱元素(AEs)和碱土元素(AEEs)的失衡会导致生殖障碍。然而,卵泡液中的 AEs/AEEs 是否与卵巢储备功能减退(DOR)这一严重的生殖系统疾病有关,目前仍不清楚:方法:在中国开展了一项巢式病例对照研究。方法:在中国进行了一项巢式病例对照研究,收集了 154 名 DOR 患者和 154 名对照者的卵泡液样本,并对其中的九种 AE/AEE 水平进行了评估。利用贝叶斯核机(BKMR)和逻辑回归估算了各元素对 DOR 的混合效应和单一效应:结果:DOR 组卵泡液中 Li、Na 和 K 的中位浓度较高(所有 P 值均为结论值):本研究揭示了一种关联,即卵泡液中 AE/AEEs 的总体浓度越高,DOR 的可能性就越大。在检测到的九种元素中,钾、锂和铯与 DOR 有显著的个体关联。我们为环境因素对女性生育能力下降的影响提供了新的线索:回顾性注册。
{"title":"Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study.","authors":"Tian Tian, Qin Li, Fang Liu, Huahua Jiang, Rui Yang, Yue Zhao, Fei Kong, Yuanyuan Wang, Xiaoyu Long, Jie Qiao","doi":"10.1186/s13048-024-01414-3","DOIUrl":"10.1186/s13048-024-01414-3","url":null,"abstract":"<p><strong>Background: </strong>Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR).</p><p><strong>Methods: </strong>A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions.</p><p><strong>Results: </strong>The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect.</p><p><strong>Conclusion: </strong>This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline.</p><p><strong>Trial registration: </strong>Retrospectively registered.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}