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Zhang M, Wang Y, Di J, Zhang X, Liu Y, Zhang Y, Li B, Qi S, Cao X, Liu L, Liu S, Xu F. High coverage of targeted lipidomics revealed lipid changes in the follicular fluid of patients with insulin-resistant polycystic ovary syndrome and a positive correlation between plasmalogens and oocyte quality. Front Endocrinol (Lausanne) 2024; 15:1414289. [PMID: 38904043 PMCID: PMC11187234 DOI: 10.3389/fendo.2024.1414289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 05/16/2024] [Indexed: 06/22/2024] Open
Abstract
Background Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown. Methods A total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent in vitro fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified. Results The number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10-3 mol/L and 10-9 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality. Conclusions This study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte in vitro maturation (IVM).
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Affiliation(s)
- Meizi Zhang
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Yuanyuan Wang
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Jianyong Di
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Xuanlin Zhang
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Ye Liu
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Yixin Zhang
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Bowen Li
- LipidAll Technologies Company Limited, Changzhou, Jiangsu, China
| | - Simeng Qi
- LipidAll Technologies Company Limited, Changzhou, Jiangsu, China
| | - Xiaomin Cao
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Li Liu
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Shouzeng Liu
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
| | - Fengqin Xu
- Reproductive Medicine Center, Tianjin First Central Hospital, Tianjin, China
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Xu X, Jiang Y, Du J, Sun H, Wang X, Zhang C. 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. J Ovarian Res 2024; 17:116. [PMID: 38807145 PMCID: PMC11134646 DOI: 10.1186/s13048-024-01437-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 05/11/2024] [Indexed: 05/30/2024] Open
Abstract
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.
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Affiliation(s)
- Xiaohang Xu
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China
| | - Yilin Jiang
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China
| | - Jinlin Du
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China
| | - Haoyue Sun
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China
| | - Xue Wang
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China
| | - Cuilian Zhang
- Reproductive Medical Center, People's Hospital of Zhengzhou University, Zhengzhou, China.
- Reproductive Medical Center, Henan Provincial People's Hospital, Zhengzhou, China.
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Fang Q, Qiao Z, Luo L, Bai S, Chen M, Zhang X, Zong L, Tong XH, Wu LM. Predictive models of recurrent implantation failure in patients receiving ART treatment based on clinical features and routine laboratory data. Reprod Biol Endocrinol 2024; 22:32. [PMID: 38509534 PMCID: PMC10953148 DOI: 10.1186/s12958-024-01203-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 03/09/2024] [Indexed: 03/22/2024] Open
Abstract
STUDY QUESTION The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. WHAT IS KNOWN ALREADY Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. STUDY DESIGN, SIZE, DURATION A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 462 patients in the RIF group and 4750 patients in the control group. The patients' basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200). MAIN RESULTS AND THE ROLE OF CHANCE (1) An increased duration of infertility (1.978; 95% CI, 1.264-3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185-4.336), low AMH levels (0.504; 95% CI, 0.275-0.922), insulin resistance (3.548; 95% CI, 1.931-6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-β2-glycoprotein I antibody (A-β2-GPI Ab)-positive status (5.515; 95% CI, 1.481-20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870-0.929) for the training cohort and 0.895 (95% CI, 0.865-0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015-1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181-0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597-0.748). LIMITATIONS, REASONS FOR CAUTION This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation. WIDER IMPLICATIONS OF THE FINDINGS Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82,201,792, 82,301,871, 81,971,446, and 82,374,212) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).
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Affiliation(s)
- Qunying Fang
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
- University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Zonghui Qiao
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Lei Luo
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Shun Bai
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Min Chen
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
- University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Xiangjun Zhang
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
- University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China
| | - Lu Zong
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China.
| | - Xian-Hong Tong
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China.
| | - Li-Min Wu
- Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China.
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Xu X, Wang X, Jiang Y, Sun H, Chen Y, Zhang C. Development and validation of a prediction model for unexpected poor ovarian response during IVF/ICSI. Front Endocrinol (Lausanne) 2024; 15:1340329. [PMID: 38505752 PMCID: PMC10949528 DOI: 10.3389/fendo.2024.1340329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/31/2024] [Indexed: 03/21/2024] Open
Abstract
Background Identifying poor ovarian response (POR) among patients with good ovarian reserve poses a significant challenge within reproductive medicine. Currently, there is a lack of published data on the potential risk factors that could predict the occurrence of unexpected POR. The objective of this study was to develop a predictive model to assess the individual probability of unexpected POR during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments. Methods The development of the nomogram involved a cohort of 10,404 patients with normal ovarian reserve [age, ≤40 years; antral follicle count (AFC), ≥5; and anti-Müllerian hormone (AMH), ≥1.2 ng/ml] from January 2019 to December 2022. Univariate regression analyses and least absolute shrinkage and selection operator regression analysis were employed to ascertain the characteristics associated with POR. Subsequently, the selected variables were utilized to construct the nomogram. Results The predictors included in our model were body mass index, basal follicle-stimulating hormone, AMH, AFC, homeostasis model assessment of insulin resistance (HOMA-IR), protocol, and initial dose of gonadotropin. The area under the receiver operating characteristic curve (AUC) was 0.753 [95% confidence interval (CI) = 0.7257-0.7735]. The AUC, along with the Hosmer-Lemeshow test (p = 0.167), demonstrated a satisfactory level of congruence and discrimination ability of the developed model. Conclusion The nomogram can anticipate the probability of unexpected POR in IVF/ICSI treatment, thereby assisting professionals in making appropriate clinical judgments and in helping patients to effectively manage expectations.
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Affiliation(s)
- Xiaohang Xu
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Xue Wang
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Yilin Jiang
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Haoyue Sun
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Yuanhui Chen
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Cuilian Zhang
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
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Guo J, Chen Y, Jiang Y, Zhang C. Effects of body mass index and insulin resistance on first-time assisted conception and perinatal outcomes in young polycystic ovary syndrome patients. Front Endocrinol (Lausanne) 2023; 14:1170816. [PMID: 37554761 PMCID: PMC10405815 DOI: 10.3389/fendo.2023.1170816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/04/2023] [Indexed: 08/10/2023] Open
Abstract
Objective The objective of the study was to explore the effect of body mass index (BMI) and insulin resistance (IR) levels on first-time assisted conception results and perinatal outcomes in young polycystic ovary syndrome (PCOS) patients. Design This was a single-center, retrospective, observational cohort study. Patients Young women with PCOS undergoing their first embryo transfer were included in the study. Main outcome measure Early pregnancy loss rate was the main outcome measure. Results The early pregnancy loss rate in the overweight + insulin resistance group (OW+IR group) was significantly higher than that in the non-overweight + non-insulin resistance group (NOW+NIR group) (18.16% vs. 9.02%, Bonferroni correction, P = 0.012). The early pregnancy loss rate in the non-overweight + insulin resistance group (NOW+IR group) and overweight + non-insulin resistance group (OW+NIR group) (18.18% and 17.14%, respectively) were also higher than that in the NOW+NIR group (6.07%), but the difference was not statistically significant (Bonferroni correction, all P > 0.05). No significant difference was found in clinical pregnancy rate, live birth rate, and macrosomia rate (all P > 0.05). After adjusting for confounding factors, BMI and IR levels were identified as independent risk factors for early pregnancy loss rate. Conclusion BMI and IR levels are independent risk factors for early pregnancy loss in young PCOS patients during the first embryo transfer cycle. Multiple indicators should be considered when assessing pregnancy outcomes, which will promote individualized pregnancy guidance and treatment procedures for PCOS patients.
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Affiliation(s)
- Jiayu Guo
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Yuanhui Chen
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Yilin Jiang
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Cuilian Zhang
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
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Hernández-Melchor D, Palafox-Gómez C, Madrazo I, Ortiz G, Padilla-Viveros A, López-Bayghen E. Surgical and nutritional interventions for endometrial receptivity: A case report and review of literature. World J Clin Cases 2022; 10:12295-12304. [PMID: 36483831 PMCID: PMC9724549 DOI: 10.12998/wjcc.v10.i33.12295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/16/2022] [Accepted: 10/17/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is an endocrine disease that combines metabolic, reproductive, and psychological dysfunctions. Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertility. Insulin resistance (IR) is a pathological state of inadequate response to insulin that affects reproduction in PCOS, as damage caused by IR at the endometrial level becomes an obstacle for embryo implantation. Reversing IR resulted in spontaneous pregnancies in PCOS patients, indicating that metabolic corrections improve endometrial dysfunctions. Mesenchymal stem-cell treatment has also corrected endometrial quality and lead to pregnancies in patients with Asherman’s syndrome. We propose a combination of nutritional intervention with the surgical placement of stem cells to improve endometrial quality to achieve pregnancy in a PCOS patient undergoing in vitro fertilization (IVF) treatment.
CASE SUMMARY After two failed IVF cycles, a metabolic intervention, consisting of a ketogenic diet with daily consumption of 50 g of carbohydrates (CH), was indicated until pregnancy. Metabolic Syndrome was assessed using the Harmonizing Definition (3 of 5 pathologies: Central obesity, hypertension, hyperglycemia, hypertriglyceridemia, and dyslipidemia), and the Homeostatic Model Assessment of IR (HOMA-IR) was used to measure the level of IR. Once IR improved, endometrial quality improved. However, two day 5-thawed embryos (euploid, donated oocyte–partner's sperm) failed to implant, suggesting endometrial quality improvement was insufficient. Therefore, transmyometrial implantation of mesenchymal stem cells from the stromal vascular fraction of adipose tissue was performed to enrich the endometrial stem cell niche. Minimal endometrial mean thickness for embryo transfer (6.9 mm) was achieved three months after stem cell treatment and continuous dietary control of IR. Two euploid-day 5-thawed embryos (donated oocyte–partner's sperm) were transferred, and embryo implantation was confirmed on day 14 by β-hCG serum levels. Currently, a 37 wk baby girl is born.
CONCLUSION In PCOS, endometrial quality can be improved by combining nutrient-based metabolic correction with endometrial stem cell niche enrichment.
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Affiliation(s)
- Dinorah Hernández-Melchor
- Science, Technology and Society Program, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México City 07360, CDMX, México
- Clinical Research, Instituto Regenera SC, México City 05320, CDMX, México
| | - Cecilia Palafox-Gómez
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México City 07360, CDMX, México
| | - Ivan Madrazo
- Investigación Clínica, Instituto de Infertilidad y Genética México SC, INGENES, México City 05320, CDMX, México
| | - Ginna Ortiz
- Investigación Clínica, Instituto de Infertilidad y Genética México SC, INGENES, México City 05320, CDMX, México
| | - America Padilla-Viveros
- Science, Technology and Society Program, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México City 07360, CDMX, México
| | - Esther López-Bayghen
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, CDMX, México
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Siahaan SCPT, Santoso B, Widjiati. Effectiveness of Moringa oleifera Leaves on TNF-α Expression, Insulin Levels, Glucose Levels and Follicle Count in Rattus norvegicus PCOS Model. Diabetes Metab Syndr Obes 2022; 15:3255-3270. [PMID: 36304481 PMCID: PMC9595062 DOI: 10.2147/dmso.s385492] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 10/16/2022] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a syndrome characterized by ovulation disorders accompanied by hyperandrogens. Women with PCOS are prone to develop insulin resistance which has metabolic characteristics similar to type 2 diabetes and leads to disturbance of follicular formation. PCOS is also known to increase the concentration of proinflammatory cytokines, namely TNF-α. Moringa oleifera leaves have been shown to have compounds that can reduce insulin levels and glucose levels in diabetes mellitus and should be able to reduce TNF-α and follicle count. PURPOSE This study aims to prove the effectiveness of Moringa oleifera leaf in reducing insulin, glucose levels, TNF-α and follicle count in PCOS. METHODS The three-month-old white rats Wistar (Rattus norvegicus) 150-170 grams were divided into four groups (n = 10), namely normal rats, PCOS model rats, PCOS model rats given metformin, and PCOS rats given 500mg of Moringa oleifera. The method of this study is taking PCOS model rats by injecting the 100mg/kg BW hormone testosterone propionate for 21 days. After 21 days of therapy, we analyzed insulin, glucose levels, TNF-α and follicle count. RESULTS The PCOS control group showed an increase in insulin level, glucose levels, TNF-α expression, and a decrease in the follicle count compared to the normal control group. The insulin level, glucose level, TNF-α and follicle count in the Moringa oleifera 500 mg/kg BW treatment group were significantly lower than in the PCOS control group. CONCLUSION Moringa oleifera leaves have the potential in reducing insulin levels, blood glucose levels, TNF-α and follicle count in PCOS patients.
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Affiliation(s)
| | - Budi Santoso
- Department of Obstetrics and Gynecology, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
| | - Widjiati
- Department of Embryology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia
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Chen Y, Guo J, Zhang Q, Zhang C. Insulin Resistance is a Risk Factor for Early Miscarriage and Macrosomia in Patients With Polycystic Ovary Syndrome From the First Embryo Transfer Cycle: A Retrospective Cohort Study. Front Endocrinol (Lausanne) 2022; 13:853473. [PMID: 35498421 PMCID: PMC9046670 DOI: 10.3389/fendo.2022.853473] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/08/2022] [Indexed: 12/16/2022] Open
Abstract
Objective The objective of the study was to explore the effect of insulin resistance on pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) from the first embryo transfer cycle. Design This was a single-center, retrospective, observational cohort study. Patients Included in the study were women with PCOS for the first embryo transfer. Main Outcome Measures Early miscarriage rate and macrosomia rate were the main outcome measures. Results With increased HOMA-IR, the early miscarriage rate (7.14, 13.21, and 16.22%, respectively; P = 0.039), macrosomia rate (5.78, 11.79, and 17.58%, respectively; P = 0.026) and the incidence of gestational diabetes (GDM) (10.00, 14.50, and 25.67% respectively; P = 0.002) significantly increased, while the live birth rate markedly decreased (63.03, 55.27, and 47.88%, respectively; P = 0.004). No significant difference was found in clinical pregnancy rate, late miscarriage rate, low birthweight rate and baby gender ratio (all P >0.05). After adjusting for confounding factors, HOMA-IR was an independent risk factor of early miscarriage rate and macrosomia rate. Conclusion Insulin resistance is an independent risk factor for early miscarriage and macrosomia in PCOS patients during the first embryo transfer cycle. It is essential to give more attention before and after pregnancy for PCOS women with high HOMA-IR.
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Affiliation(s)
- Yuanhui Chen
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Jiayu Guo
- Reproductive Medical Center, People’s Hospital of Zhengzhou University, Zhengzhou, China
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Qingwen Zhang
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Cuilian Zhang
- Reproductive Medical Center, Henan Provincial People’s Hospital, Zhengzhou, China
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The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome. Mol Biol Rep 2022; 49:875-884. [PMID: 35040006 DOI: 10.1007/s11033-021-06833-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/12/2021] [Indexed: 10/19/2022]
Abstract
RESEARCH QUESTION The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. DESIGN Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3β-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. RESULT Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. CONCLUSION Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.
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Moradi A, Ghasemian F, Mashayekhi F. The reaggregation of normal granulosa-cumulus cells and mouse oocytes with polycystic ovarian syndrome in vitro: An experimental study. Int J Reprod Biomed 2022; 19:987-996. [PMID: 34977456 PMCID: PMC8717076 DOI: 10.18502/ijrm.v19i11.9914] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 12/12/2020] [Accepted: 03/06/2021] [Indexed: 11/24/2022] Open
Abstract
Background The dialogue between oocytes and their surrounding cells plays a major role in the progress of oocyte meiosis and their developmental potential. Objective This study aimed to evaluate the effect of co-culture of normal granulosa-cumulus cells (GCCs) with oocytes from polycystic ovarian syndrome (PCOS) mice. Materials and Methods Normal GCCs were collected from 10 virgin adult Naval Medical Research Institute female mice (30-35 gr, 7-8 wk old), and were cultured in an alpha-minimum essential medium supplemented with 5% fetal calf serum for 24-48 hr (1×106 cells/well). Then, germinal-vesicle oocytes from PCOS mice were cultured in the presence of cultured normal GCCs (experimental group) and without GCCs (control group). The maturation rate and quality of the PCOS oocytes were examined by evaluating TFAM and Cx43 gene expression (real-time PCR) and the connection among PCOS oocytes and normal GCCs after 24 hr of culture. Results The co-culture of normal GCCs and PCOS oocytes in the experimental group led to the formation of a complex called a PCOS oocyte-normal GCCs complex. The maturation rate of these complexes was significantly increased compared to that of the control group (p ≤ 0.001). A significant difference was also found in the expression of Cx43 (p ≤ 0.001) and TFAM (p < 0.05) genes in the experimental group compared with the control group. The connection between PCOS oocytes and normal GCCs was observed in the scanning electron microscope images. Conclusion Co-culture with normal GCCs improves the capacity of PCOS oocytes to enter meiosis, which may result in the promotion of assisted reproduction techniques.
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Affiliation(s)
- Amaneh Moradi
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Fatemeh Ghasemian
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Farhad Mashayekhi
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
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Naigaonkar A, Dadachanji R, Hinduja I, Mukherjee S. Altered redox status may contribute to aberrant folliculogenesis and poor reproductive outcomes in women with polycystic ovary syndrome. J Assist Reprod Genet 2021; 38:2609-2623. [PMID: 34041658 PMCID: PMC8581097 DOI: 10.1007/s10815-021-02241-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 05/18/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Women with polycystic ovary syndrome (PCOS) are often infertile and opt for artificial reproductive techniques (ART) to conceive. Disrupted pro-/antioxidant balance in oocyte microenvironment may contribute towards sub-optimal oocyte/embryo quality and poor ART outcome in them. METHODS Activities/levels of redox markers and their transcript expression were investigated in follicular fluid and granulosa cells respectively, in women with PCOS (n = 71) and controls (n = 50) undergoing in vitro fertilization (IVF). Correlation analysis of redox markers and IVF parameters was performed. RESULTS Activities of superoxide dismutase, glutathione reductase, glutathione peroxidase, and paraoxonase1 were significantly lower in follicular fluid of PCOS women than in controls. Levels of lipid peroxidation, oxidative protein modification, and oxidized glutathione were higher, whereas those of total antioxidant capacity, total thiols, and reduced glutathione were lower in follicular fluid of PCOS women than in controls. Further, comparison of redox markers based on insulin resistance and BMI status of study participants showed similar trends, indicating that PCOS pathophysiology is a significant contributor to oxidative stress irrespective of insulin resistance and BMI. Transcript levels of antioxidant enzymes were lower in granulosa cells from PCOS women than in controls, and they accorded with their activities in follicular fluid. Moreover, few redox markers showed significant correlations with oocyte/embryo quality and pregnancy outcome. CONCLUSION Our data indicates disrupted redox homeostasis in follicular environment in PCOS which may negatively influence oocyte/embryo quality. Further, granulosa cells may play crucial role in maintaining follicular redox homeostasis. Glutathione system and paraoxonase1 could be explored further as surrogates for IVF prognosis/outcome.
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Affiliation(s)
- Aalaap Naigaonkar
- Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J.M. Street, Parel, Mumbai, Maharashtra 400012 India
| | - Roshan Dadachanji
- Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J.M. Street, Parel, Mumbai, Maharashtra 400012 India
| | - Indira Hinduja
- Hinduja IVF Centre, P. D. Hinduja National Hospital and Medical Research Centre, Mahim, Mumbai, Maharashtra 400016 India
| | - Srabani Mukherjee
- Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, J.M. Street, Parel, Mumbai, Maharashtra 400012 India
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Dietary Carbohydrate Intake, Dietary Glycemic Load and Outcomes of In Vitro Fertilization: Findings from an Observational Italian Cohort Study. Nutrients 2020; 12:nu12061568. [PMID: 32481483 PMCID: PMC7352402 DOI: 10.3390/nu12061568] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 05/19/2020] [Accepted: 05/26/2020] [Indexed: 11/23/2022] Open
Abstract
In recent decades, increasing attention has been paid to the influence of diet on reproductive health. Carbohydrates in diet affect glucose metabolism and multiple evidences showed the key role of insulin sensitivity in regulating female fertility. We designed a prospective cohort study to investigate the relation between dietary carbohydrate intake, glycemic load (GL) and the outcomes of assisted reproduction. A population of 494 female partners of couples referring to an Italian Fertility Center and eligible for in vitro fertilization (IVF) were enrolled in the study. On the day of the oocyte retrieval, information on their diet was obtained using a validated food frequency questionnaire (FFQ). We calculated the relative risk and 95% confidence interval of embryo transfer, clinical pregnancy and live birth according to the following dietary exposures: GL, glycemic index (GI) as well as the daily carbohydrate and fiber intake. A multiple regression model was used to account for the confounders. After adjusting for age, college degree, body mass index (BMI), leisure physical activity and previous assisted reproduction techniques (ART) cycles, no significant association was observed between the considered dietary exposures and the IVF outcomes. The roles of GL, carbohydrate intake and GI were assessed in strata of the cause of infertility and body mass index and no relation emerged in this further analysis. We found no clear association between the dietary carbohydrate quantity and quality and IVF outcomes in a cohort of infertile Italian women.
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