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Feng J, Luo R, Gao J, Wang Y, Cong J, Ma H, Wu X. Elevated Triglyceride-Glucose Index Is Associated With Insulin Resistance, Metabolic Syndrome Components, Nonalcoholic Fatty Liver Disease, and Adverse Pregnancy Outcomes in Chinese Women With Polycystic Ovary Syndrome. Clin Endocrinol (Oxf) 2025. [PMID: 40298068 DOI: 10.1111/cen.15252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 03/20/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025]
Abstract
AIM To investigate the associations of triglyceride-glucose index (TyG) with anthropometric characteristics, metabolic/endocrine profiles, and pregnancy outcomes in Chinese women with polycystic ovary syndrome (PCOS). METHODS This secondary analysis of the Acupuncture and Clomiphene for Chinese Women with Polycystic Ovary Syndrome trial (PCOSAct) included 956 participants with prospectively collected data. TyG was calculated using fasting triglyceride and glucose levels (Ln [TG (mg/dL) × FPG (mg/dL)/2]). Linear regression and trend analyses evaluated relationships between TyG and clinical parameters. Receiver operating characteristic (ROC) curves assessed TyG's predictive capacity for insulin resistance (IR), metabolic syndrome (MS), and nonalcoholic fatty liver disease (NAFLD). Multivariable logistic regression estimated risks for metabolic outcomes and pregnancy outcomes. RESULTS Linear trends revealed that the TyG was positively associated with age, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, FPG, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, triglycerides, low-density lipoprotein (LDL), apolipoprotein B, free androgen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the prevalence of IR, MS, and NAFLD across various standards. Conversely, TyG was negatively correlated with the quantitative insulin sensitivity check index (QUICKI), high-density lipoprotein (HDL), apolipoprotein A1, sex hormone-binding globulin (SHBG), and the prevalence of ovulation per cycle, conception, pregnancy, and live birth. After adjusting for age and BMI, a significant linear relationship was observed between TyG and components of MS, IR markers, and ALT. The ROC curve analysis indicated that the AUCMS-IDF was 0.871 (95% CI: 0.846-0.896), with a sensitivity of 81.4% and specificity of 81.2% at a cut-off value of 8.745, and the AUCIR-HOMA-IR was 0.782 (95% CI: 0.753-0.811), with 71.9% sensitivity and 70.3% specificity at a cut-off of 8.585, and the AUCNAFLD was 0.705 (95% CI: 0.644-0.766), with 76.8% sensitivity and 59.3% specificity at a cut-off value of 8.665. Logistic regression analysis demonstrated that participants in the highest quartile (Q4) of TyG had significantly higher odds ratios (OR) for MS (OR: 38.36, 95% CI: 20.03-73.46, P-trend < 0.001) and IR (OR: 12.49, 95% CI: 7.3-21.35, P-trend < 0.001) compared to those in the lowest quartile (Q1), while NAFLD showed a marginal association (OR: 2.56, 95% CI: 1.00-6.55, P-trend = 0.069) after adjusting for confounding factors. Conversely, participants in Q1 of TyG had higher OR of conception (OR: 1.56, 95% CI: 1.04-2.35, p < 0.05), pregnancy (OR: 2.35, 95% CI: 1.46-3.79, p < 0.01), and live birth (OR: 2.32, 95% CI: 1.42-3.78, p < 0.01) compared to those in Q4 after adjusting for treatments. CONCLUSIONS Elevated TyG index strongly associates with adverse metabolic trajectories, and adverse pregnancy outcomes in PCOS patients. This biomarker shows particular utility for identifying metabolic dysfunction, suggesting clinical potential for risk stratification in PCOS management.
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Affiliation(s)
- Jiaxing Feng
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Rong Luo
- Jiangxi Chest Hospital, Nanchang, China
| | - Jingshu Gao
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yu Wang
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jing Cong
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hongli Ma
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaoke Wu
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Li XL, Ji YF, Feng Y, Liu SW. Metabolic disparities between obese and non-obese patients with polycystic ovary syndrome: implications for endometrial receptivity indicators. Gynecol Endocrinol 2024; 40:2312895. [PMID: 38444321 DOI: 10.1080/09513590.2024.2312895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 01/25/2024] [Indexed: 03/07/2024] Open
Abstract
OBJECTIVE To investigate the differences in the metabolic indicators and sex hormones between obese and non-obese patients with polycystic ovary syndrome (PCOS), and their impacts on endometrial receptivity (ER). METHODS We selected 255 individuals with PCOS, and categorized them into the obese groups, including the OP group (obese patients with PCOS) and the ON group (obese patients without PCOS), and selected 64 individuals who were categorized in the non-obese groups, namely, the control groups, which comprise the NP group (non-obese patients with PCOS) and the NN group(non-obese patients without PCOS). The one-way analysis of variance (ANOVA) and Mann-Whitney U tests were used to compare the metabolic indicators, and sex hormone-associated and ER-associated indicators between the groups. The correlation between the aforementioned clinical markers and ER was analyzed using the Pearson's correlation coefficient. RESULTS (1) In comparison with the NP group, the OP group exhibited higher levels (p < .01) of free androgen index (FAI), anti-müllerian hormone (AMH), fasting insulin (FINS), insulin level within 60 min, 120 min, and 180 min-60minINS, 120minINS, and 180minINS, respectively, fasting blood glucose (FBG), blood glucose level within two hours (2hGlu), homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), waist-to-hip ratio (WHR), waist circumference, hip circumference, the ratio of the maximum blood flow velocity of the uterine artery during systole to the blood flow velocity of the uterine artery at the end of diastole (uterine artery S/D), and blood flow resistance index (RI) of the uterine artery. In comparison with the NP group, the OP group exhibited lower levels (p < .01) of sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), high molecular weight adiponectin (HMWA), and high-density lipoprotein cholesterol (HDL-C). (2) In the PCOS group, RI was significantly positively correlated with FAI, FINS, 120minINS, HOMA-IR, and WHR (p < .01), and significantly negatively correlated with SHBG, HDL-C, and HMWA (p < .01); uterine artery S/D was significantly positively correlated with FAI, FINS, 2hGlu, HOMA-IR, LDL-C, and WHR (p < .01), significantly positively correlated with 120minINS and FBG (p < .05), and significantly negatively correlated with SHBG and HMWA (p < .01). CONCLUSION (1) The OP group exhibited obvious metabolic disorders and poor ER, which was manifested as low levels of SHBG and HMWA, and high levels of FAI, HOMA-IR, WHR, uterine artery S/D, and RI. (2) In patients with PCOS, there was a substantial correlation between ER-associated indicators RI and uterine artery S/D and FAI, FINS, 120minINS, HOMA-IR, WHR, SHBG, and HMWA.
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Affiliation(s)
- Xiao-Li Li
- Department of Endocrinology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan-Fei Ji
- Department of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Yu Feng
- Department of Endocrinology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shi-Wei Liu
- Department of Endocrinology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wang Y, Ssengonzi R, Townley-Tilson WHD, Kayashima Y, Maeda-Smithies N, Li F. The Roles of Obesity and ASB4 in Preeclampsia Pathogenesis. Int J Mol Sci 2024; 25:9017. [PMID: 39201703 PMCID: PMC11354233 DOI: 10.3390/ijms25169017] [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: 07/12/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/03/2024] Open
Abstract
Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. Preeclampsia affects 5-8% of pregnancies in the United States, causing a significant public health and economic burden. Despite extensive research, the etiology and pathogenesis of preeclampsia remain elusive, but have been correlated with maternal conditions such as obesity. In recent decades, the incidence of preeclampsia increased along with the prevalence of obesity among women of reproductive age. Maternal obesity has been shown to negatively affect pregnancy in almost all aspects. However, the precise mechanisms by which obesity influences preeclampsia are unclear. Ankyrin repeat and SOCS Box Containing protein 4 (ASB4) is an E3 ubiquitin ligase that can promote the degradation of a wide range of target proteins. ASB4-null mice display a full spectrum of preeclampsia-like phenotypes during pregnancy including hypertension, proteinuria, and decreased litter size. Furthermore, maternal obesity induced by a high-fat diet aggravates preeclampsia-like phenotypes in pregnant mice lacking ASB4. Variants in the ASB4 gene have been associated with obesity in humans, and a functional connection between the ASB4 gene and obesity has been established in mice. This review discusses the connections between preeclampsia, obesity, and ASB4.
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Affiliation(s)
| | | | | | | | | | - Feng Li
- Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA; (Y.W.)
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Li F, Qi JJ, Li LX, Yan TF. Impact of insulin resistance on IVF/ICSI outcomes in women with polycystic ovary syndrome: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2024; 299:54-61. [PMID: 38838387 DOI: 10.1016/j.ejogrb.2024.05.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 05/22/2024] [Accepted: 05/31/2024] [Indexed: 06/07/2024]
Abstract
OBJECTIVE To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). STUDY DESIGN PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta-analysis. RESULTS The systematic review and meta-analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: -2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: -0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: -1.54 to -0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: -1. 78 to -0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group. CONCLUSION In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary.
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Affiliation(s)
- Feng Li
- Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311 Hainan Province, China
| | - Ju-Ju Qi
- The First Hospital of Shijiazhuang, Shijiazhuang 050011, Heibei Province, China
| | - Li-Xin Li
- The First Hospital of Shijiazhuang, Shijiazhuang 050011, Heibei Province, China
| | - Teng-Fei Yan
- Baoding No.1 Central Hospital, Baoding 071000, Hebei Province, China.
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Hu Z, Zeng R, Tang Y, Liao Y, Li T, Qin L. Effect of oral glucose tolerance test-based insulin resistance on embryo quality in women with/without polycystic ovary syndrome. Front Endocrinol (Lausanne) 2024; 15:1413068. [PMID: 38978625 PMCID: PMC11228294 DOI: 10.3389/fendo.2024.1413068] [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: 04/06/2024] [Accepted: 06/07/2024] [Indexed: 07/10/2024] Open
Abstract
Objective To explore the effects of insulin resistance (IR) on embryo quality and pregnancy outcomes in women with or without polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Methods A retrospective cohort study concerning patients with/without PCOS who received gonadotropin-releasing hormone (GnRH)-antagonist protocol for IVF/ICSI from January 2019 to July 2022 was conducted. All the patients included underwent oral glucose tolerance test plus the assessment of insulin release within 6 months before the controlled ovarian stimulation. The Matsuda Index was calculated to diagnose IR. Two populations (PCOS and non-PCOS) were included and each was divided into IR and non-IR groups and analyzed respectively. The primary outcome was the high-quality day 3 embryo rate. Results A total of 895 patients were included (751 with PCOS and 144 without PCOS). For patients with PCOS, the IR group had a lower high-quality day 3 embryo rate (36.8% vs. 39.7%, p=0.005) and available day 3 embryo rate (67.2% vs. 70.6%, p<0.001). For patients without PCOS, there was no significant difference between the IR and non-IR groups in high-quality day 3 embryo rate (p=0.414) and available day 3 embryo rate (p=0.560). There was no significant difference in blastocyst outcomes and pregnancy outcomes for both populations. Conclusion Based on the diagnosis by the Matsuda Index, IR may adversely affect the day 3 embryo quality in patients with PCOS but not pregnancy outcomes. In women without PCOS, IR alone seems to have less significant adverse effects on embryo quality than in patients with PCOS. Better-designed studies are still needed to compare the differences statistically between PCOS and non-PCOS populations.
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Affiliation(s)
- Zhengyan Hu
- The Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Rujun Zeng
- The Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Yuanting Tang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yingjun Liao
- Department of Outpatient, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Tao Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Lang Qin
- The Reproductive Medical Center, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
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Chang J, Pan X, Gao J, Zhuo Y, Jiang X, Che L, Lin Y, Fang Z, Feng B, Li J, Hua L, Zhao X, Zhang R, Wu D, Xu S. Revealing the mechanism of fiber promoting sow embryo implantation by altering the abundance of uterine fluid proteins: A proteomic perspective. J Proteomics 2024; 297:105123. [PMID: 38364904 DOI: 10.1016/j.jprot.2024.105123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 02/05/2024] [Accepted: 02/07/2024] [Indexed: 02/18/2024]
Abstract
Many studies have shown that fiber in the diet plays an important role in improving the reproductive performance of sows, but there is rarely research on the impact of fiber on early embryo implantation. This study used 4D-Label free technology to identify and analyze the effect of the fiber composition in the diet on the protein in the early pregnancy uterine fluid (UF) of sows. The results indicate that ratio of insoluble fibers to soluble fibers (ISF/SF) 4.89 can increase the concentration of progesterone (PROG) and reduce tumor necrosis factorα (TNF-α) concentration in sow UF. In addition, through 4D-Label free, we identified a total of 4248 proteins, 38 proteins abundance upregulated and 283 proteins abundance downregulated in UF. Through enrichment analysis of these differential abundance proteins (DAPs), it was found that these differential proteins are mainly related to the docking of extracellular vesicles, vesicular transport, inflammatory response, and insulin resistance. Therefore, the results of this study reveal the possible mechanism by which fiber improves the reproductive performance of sows, laying a theoretical foundation for future research on the effects of diet on reproduction. SIGNIFICANCE: This study demonstrates the importance of dietary fiber for early embryo implantation in sows. The effect of dietary ISF/SF on early embryo implantation in sows was elucidated from a proteomic perspective through 4D-Label free technology. This study not only has significant implications for improving sow reproductive efficiency, but also provides important theoretical references for studying early miscarriage and reproductive nutrition in human pregnancy.
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Affiliation(s)
- Junlei Chang
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Xujing Pan
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Junjie Gao
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Yong Zhuo
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Xuemei Jiang
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Lianqiang Che
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China
| | - Yan Lin
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Zhengfeng Fang
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China
| | - Bin Feng
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China
| | - Jian Li
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China
| | - Lun Hua
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Xilun Zhao
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Ruinan Zhang
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - De Wu
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR China.
| | - Shengyu Xu
- Animal Disease-Resistance Nutrition, Ministry of Education, Ministry of Agriculture and Rural Affairs, Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, PR 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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Wu Y, Liu C, Huang J, Wang F. Quantitative proteomics reveals pregnancy prognosis signature of polycystic ovary syndrome women based on machine learning. Gynecol Endocrinol 2024; 40:2328613. [PMID: 38497425 DOI: 10.1080/09513590.2024.2328613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 03/05/2024] [Indexed: 03/19/2024] Open
Abstract
OBJECTIVE We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods. 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Yuanyuan Wu
- Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Cai Liu
- Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou, China
| | - Jinge Huang
- Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Fang Wang
- Department of Reproductive Medicine, Lanzhou University Second Hospital, Lanzhou, China
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Jiang NX, Zhao WJ, Shen HR, Du DF, Li XL. Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility. J Ovarian Res 2024; 17:31. [PMID: 38310251 PMCID: PMC10837998 DOI: 10.1186/s13048-023-01334-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/25/2023] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia. METHODS We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation. RESULTS Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein. CONCLUSIONS Our research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.
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Affiliation(s)
- Nan-Xing Jiang
- Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
| | - Wei-Jie Zhao
- Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
| | - Hao-Ran Shen
- Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
| | - Dan-Feng Du
- Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China
| | - Xue-Lian Li
- Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China.
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, People's Republic of China.
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Yang X, Xiaoping W, Nan D, Jian Z, Xiaofeng L, Liwei Y, Zhao M, Wang F. Proteomic and bioinformatic analysis of human endometrium from polycystic ovarian syndrome with and without insulin resistance. Gynecol Endocrinol 2023; 39:2173948. [PMID: 36750132 DOI: 10.1080/09513590.2023.2173948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
Objective: The aim of this study was to investigate the endometrial proteomic profiles of patients with polycystic ovary syndrome (PCOS) with and without insulin resistance (IR). Method of Study: We collected 40 endometrial samples, including PCOS-IR (n = 21), PCOS-non-IR (n = 12), and control (n = 7). Data-independent acquisition (DIA)-based proteomics method is used to identify the expressed proteins among the three groups. The correlation between pregnancy outcomes and identified proteins was analyzed by Lasso regression. Results: A total of 5331 proteins were identified, while 275 proteins were differentially expressed in the PCOS vs. control group and 215 proteins were differentially expressed in the PCOS-IR vs. PCOS-non-IR group. Platelet degranulation, neutrophil degranulation, and very long-chain fatty acid catabolic processes have been found to play important roles in the endometrium of patients with PCOS-IR. Lasso regression analysis found that ACTR1A, TSC22D2, CKB, ABRAXAS2, and TAGLN2 were associated with miscarriage in patients with PCOS. ACTR1A and CKB were higher in the PCOS-IR group and were positively correlated with HOMA-IR (p < .05). Conclusion: In this study, a panel of proteins was found to be differently expressed in the endometrium. ACTR1A and CKB may be considered as PCOS-IR candidate biomarkers.
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Affiliation(s)
- Xin Yang
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Wang Xiaoping
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Ding Nan
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Zhang Jian
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Li Xiaofeng
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Yuan Liwei
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Mengni Zhao
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
| | - Fang Wang
- Reproductive Medicine Center, Second Hospital of Lanzhou University, Lanzhou, China
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Wang X, Li Y, Tan H, Cai S, Ma S, Peng Y, Guo H, Li X, Tang Y, Zhang S, Lin G, Gong F. Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study. Reprod Biol Endocrinol 2023; 21:101. [PMID: 37891650 PMCID: PMC10605334 DOI: 10.1186/s12958-023-01154-x] [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: 03/29/2023] [Accepted: 10/15/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND The current routine endometrial preparation protocol for women with polycystic ovary syndrome (PCOS) is hormone replacement treatment (HRT). Letrozole is rarely used in frozen embryo cycles. Evidence confirming whether letrozole-stimulated (LS) protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable remains lacking. METHODS This was a retrospective cohort study involving all frozen embryo transfer cycles with LS and HRT for PCOS during the period from Jan 2019 to December 2020 at a tertiary care center. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between LS and HRT protocols after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which LS protocol was suitable. RESULTS The results of multivariate logistic regression showed that LS was significantly associated with a higher clinical pregnancy rate (70.9% vs. 64.4%;aOR:1.41, 95%CI: 1.18,1.68), live birth rate (60.5% vs. 51.4% aOR:1.49, 95%CI: 1.27,1.76), and a lower risk of miscarriage (14.7% vs. 20.1% aOR: 0.68, 95%CI: 0.53,0.89), hypertensive disorders of pregnancy (6.7% vs. 8.9% aOR: 0.63, 95%CI: 0.42,0.95), and gestational diabetes mellitus (16.7% vs. 20.7% aOR:0.71, 95%CI: 0.53,0.93) than HRT. There were no significant differences in other outcomes such as preterm birth, cesarean delivery, small for gestational age, or large for gestational age between the two endometrial preparation protocols. Subgroup analysis showed that LS had higher live birth rates than HRT in most of the subgroups; in the three subgroups of maternal age ≥ 35 years, menstrual cycle < 35 days, and no insulin resistance, the live birth rates of the two endometrial preparation protocols were comparable. CONCLUSIONS LS protocol could improve the live birth rate and reduce the incidence of miscarriage, hypertensive disorders of pregnancy and gestational diabetes mellitus in patients with PCOS. LS protocol is suitable for all types of patients with PCOS. LS should be considered the preferred endometrial preparation protocol for women with PCOS.
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Affiliation(s)
- Xiaojuan Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, 410008, Hunan, China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Yuan Li
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Hongzhuan Tan
- Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, 410008, Hunan, China
| | - Sufen Cai
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Shujuan Ma
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Yangqin Peng
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Hui Guo
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Xiaofeng Li
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Yi Tang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Shunji Zhang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
| | - Ge Lin
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China
- Laboratory of Reproductive and Stem Cell Engineering, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China
| | - Fei Gong
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, NO. 567 Tongzipo West Road, Yuelu District, Changsha city, 410008, Hunan Province, China.
- Laboratory of Reproductive and Stem Cell Engineering, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008, Hunan, China.
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12
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Wang X, Cai S, Tang S, Yang L, Tan J, Sun X, Gong F. Effect of lifestyle or metformin interventions before IVF/ICSI treatment on infertile women with overweight/obese and insulin resistance: a factorial design randomised controlled pilot trial. Pilot Feasibility Stud 2023; 9:160. [PMID: 37700375 PMCID: PMC10496164 DOI: 10.1186/s40814-023-01388-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 08/29/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND For infertile women with overweight/obesity and insulin resistance (IR), it is uncertain whether intervention before infertility treatment can improve live birth rate (LBR). We implemented a factorial-design study to explore the effectiveness of lifestyle and metformin interventions. This pilot study aimed to evaluate the feasibility of a definitive study. METHODS We randomised 80 women without polycystic ovarian syndrome (PCOS) who planned to start their first or second IVF/ICSI treatment with a body mass index ≥ 25 kg/m2 and IR. Participants were randomised (1:1:1:1) into four groups: (A) lifestyle intervention, (B) metformin intervention, (C) lifestyle + metformin intervention, or (D) no intervention. All interventions were performed before IVF/ICSI treatment. RESULTS During 10 months, 114 women were screened and eligible; 80 were randomised, and 72 received the assigned treatment. The recruitment rate was 70.18% (80/114, 95% CI 61.65%-78.70%). An average of 10 participants were randomised each month. None of the participants crossed over from one group to another. Approximately 93.15% (68/73) of the participants achieved good intervention compliance. Only 77.78% (56/72) of the recruited participants started infertility treatment after achieving the goal of the intervention. All randomised participants completed the follow-up. Mild adverse events after metformin administration were reported in 43.24% (16/37) of the cases, although no serious adverse events related to the interventions occurred. The LBR for groups A + C and B + D were 33.33% (12/36) and 33.33% (12/36) (RR = 1.00, 95%CI:0.52-1.92) (lifestyle intervention effect). The LBR for groups B + C and A + D were 43.24% (16/37) and 22.86% (8/35) (RR = 1.89, 95% CI:0.93-3.86) (metformin intervention effect). There was no evidence for an intervention interaction between lifestyle and metformin. We cannot yet confirm the effects of lifestyle, metformin, or their interaction owing to the insufficient sample size in this pilot study. CONCLUSIONS Instituting a 2 × 2 factorial design randomized controlled trial (RCT) is feasible, as the pilot study showed a high recruitment rate and compliance. There is no evidence that lifestyle or metformin improves live birth, and adequately powered clinical trials are required. TRIAL REGISTRATION clinicaltrials.gov NCT03898037. Registered: April 1, 2019.
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Affiliation(s)
- Xiaojuan Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, 410008 Hunan China
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008 Hunan China
| | - Sufen Cai
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008 Hunan China
| | - Sha Tang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008 Hunan China
| | - Lanlin Yang
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008 Hunan China
| | - Jing Tan
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041 Sichuan China
| | - Xin Sun
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041 Sichuan China
| | - Fei Gong
- Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-XIANGYA, Changsha, 410008 Hunan China
- Laboratory of Reproductive and Stem Cell Engineering, Key Laboratory of National Health and Family Planning Commission, Central South University, Changsha, 410008 Hunan China
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Jiang H, Si M, Tian T, Shi H, Huang N, Chi H, Yang R, Long X, Qiao J. Adiposity and lipid metabolism indicators mediate the adverse effect of glucose metabolism indicators on oogenesis and embryogenesis in PCOS women undergoing IVF/ICSI cycles. Eur J Med Res 2023; 28:216. [PMID: 37400924 DOI: 10.1186/s40001-023-01174-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 06/14/2023] [Indexed: 07/05/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) women have high incidences of dyslipidemia, obesity, impaired glucose tolerance (IGT), diabetes, and insulin resistance (IR) and are fragile to female infertility. Obesity and dyslipidemia may be the intermediate biological mechanism for the associations between glucose metabolism dysfunction and abnormal oogenesis and embryogenesis. METHODS This retrospective cohort study was performed at a university-affiliated reproductive center. A total of 917 PCOS women aged between 20 and 45 undergoing their first IVF/ICSI embryo transfer cycles from January 2018 to December 2020 were involved. Associations between glucose metabolism indicators, adiposity and lipid metabolism indicators, and IVF/ICSI outcomes were explored using multivariable generalized linear models. Mediation analyses were further performed to examine the potential mediation role of adiposity and lipid metabolism indicators. RESULTS Significant dose-dependent relationships were found between glucose metabolism indicators and IVF/ICSI early reproductive outcomes and between glucose metabolism indicators and adiposity and lipid metabolism indicators (all P < 0.05). Also, we found significant dose-dependent relationships between adiposity and lipid metabolism indicators and IVF/ICSI early reproductive outcomes (all P < 0.05). The mediation analysis indicated that elevated FPG, 2hPG, FPI, 2hPI, HbA1c, and HOMA2-IR were significantly associated with decreased retrieved oocyte count, MII oocyte count, normally fertilized zygote count, normally cleaved embryo count, high-quality embryo count, or blastocyst formation count after controlling for adiposity and lipid metabolism indicators. Serum TG mediated 6.0-31.0% of the associations; serum TC mediated 6.1-10.8% of the associations; serum HDL-C mediated 9.4-43.6% of the associations; serum LDL-C mediated 4.2-18.2% of the associations; and BMI mediated 26.7-97.7% of the associations. CONCLUSIONS Adiposity and lipid metabolism indicators (i.e., serum TG, serum TC, serum HDL-C, serum LDL-C, and BMI) are significant mediators of the effect of glucose metabolism indicators on IVF/ICSI early reproductive outcomes in PCOS women, indicating the importance of preconception glucose and lipid management and the dynamic equilibrium of glucose and lipid metabolism in PCOS women.
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Affiliation(s)
- Huahua Jiang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Manfei Si
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Tian Tian
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Huifeng Shi
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- National Centre for Healthcare Quality Management in Obstetrics, Beijing, China
| | - Ning Huang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Hongbin Chi
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Rui Yang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China
| | - Xiaoyu Long
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
| | - Jie Qiao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing, China.
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
- Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.
- Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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14
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Gao R, Qin L, Li Z, Min W. The homeostasis model assessment of insulin resistance is a judgment criterion for metformin pre-treatment before IVF/ICSI and embryo transfer cycles in patients with polycystic ovarian syndrome. Front Endocrinol (Lausanne) 2023; 14:1106276. [PMID: 36843612 PMCID: PMC9946957 DOI: 10.3389/fendo.2023.1106276] [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: 11/23/2022] [Accepted: 01/26/2023] [Indexed: 02/11/2023] Open
Abstract
PURPOSE The aim of this study was to explore the value of the homeostasis model assessment of IR (HOMA-IR) as a judgment criterion for metformin pre-treatment before in vitro fertilization/intracellular sperm injection (IVF/ICSI) and embryo transfer (ET) for polycystic ovarian syndrome (PCOS) patients. MATERIALS AND METHODS The clinical and laboratory information of PCOS patients who received IVF/ICSI-ET from January 2017 to September 2021 was retrospectively analyzed. We compared the clinical pregnancy rate (primary outcome) and controlled ovarian stimulation (COS)-related parameters (secondary outcomes) between patients with and without metformin pre-treatment for all PCOS patients not grouped by HOMA-IR, PCOS patients with HOMA-IR < 2.71, and PCOS patients with HOMA-IR ≥ 2.71. RESULTS A total of 969 PCOS patients who received the GnRH-antagonist protocol were included in this study. For all PCOS patients, the metformin group showed comparable clinical pregnancy rates in fresh ET cycles and frozen ET cycles compared with the control group (55.9% vs. 57.1%, p = 0.821 and 63.8% vs. 60.9%, p = 0.497). For PCOS patients with HOMA-IR < 2.71, the clinical pregnancy rates in both fresh ET cycles and frozen ET cycles were statistically similar between the two groups (61.5% vs. 57.6%, p = 0.658 and 70.6% vs. 66.7%, p = 0.535). For PCOS patients with HOMA-IR ≥ 2.71, the clinical pregnancy rate in fresh ET cycles was comparable between the two groups (51.5% vs. 56.3, p = 0.590), but it was statistically higher in the metformin group than in the control group in frozen ET cycles (57.1% vs. 40.0%, p = 0.023). The metformin group had less oocytes retrieved, a lower cleaved oocyte rate, a lower available D3 embryo rate, a lower blastocyst formation rate, and a lower available blastocyst rate than the control group. CONCLUSION HOMA-IR is a judgment criterion for metformin pre-treatment before IVF/ICSI-ET in patients with PCOS. Metformin pre-treatment could be added for PCOS patients with HOMA-IR ≥ 2.71 during frozen IVF/ICSI-ET cycles to improve the clinical pregnancy rate.
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Affiliation(s)
- Rui Gao
- The Reproductive Medical Center, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Lang Qin
- The Reproductive Medical Center, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Zhengyu Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China
- *Correspondence: Zhengyu Li, ; Wenjiao Min,
| | - Wenjiao Min
- Psychosomatic Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
- *Correspondence: Zhengyu Li, ; Wenjiao Min,
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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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Inflammatory and metabolic markers in relation to outcome of in vitro fertilization in a cohort of predominantly overweight and obese women. Sci Rep 2022; 12:13331. [PMID: 35922472 PMCID: PMC9349206 DOI: 10.1038/s41598-022-17612-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 07/28/2022] [Indexed: 11/09/2022] Open
Abstract
For overweight and obese women undergoing in vitro fertilization (IVF) the pregnancy and live birth rates are compromised while the underlying mechanisms and predictors are unclear. The aim was to explore the association between adipose tissue-related inflammatory and metabolic markers and the pregnancy and live birth outcome of IVF in a cohort of predominantly overweight and obese women. Serum samples, fulfilling standardizing criteria, were identified from 195 women having participated in either the control (n = 131) or intervention (n = 64) group of a randomized controlled trial (RCT), seeking to evaluate the effect of a weight reduction intervention on IVF outcome in obese women. Serum high-sensitivity C-reactive protein (hsCRP) and the adipokines leptin and adipocyte fatty acid-binding protein (AFABP) were analyzed for the whole cohort (n = 195) in samples collected shortly before IVF [at randomization (control group), after intervention (intervention group)]. Information on age, anthropometry [BMI, waist circumference, waist-to-height ratio (WHtR)], pregnancy and live birth rates after IVF, as well as the spontaneous pregnancy rate, was extracted or calculated from collected data. The women of the original intervention group were also characterized at randomization regarding all variables. Eight women [n = 3 original control group (2.3%), n = 5 original intervention group (7.8%)] conceived spontaneously before starting IVF. BMI category proportions in the cohort undergoing IVF (n = 187) were 1.6/20.1/78.3% (normal weight/overweight/obese). The pregnancy and live birth rates after IVF for the cohort were 35.8% (n = 67) and 24.6% (n = 46), respectively. Multivariable logistic regression revealed that none of the variables (age, hsCRP, leptin, AFABP, BMI, waist circumference, WHtR) were predictive factors of pregnancy or live birth after IVF. Women of the original intervention group displayed reductions in hsCRP, leptin, and anthropometric variables after intervention while AFABP was unchanged. In this cohort of predominantly overweight and obese women undergoing IVF, neither low-grade inflammation, in terms of hsCRP, other circulating inflammatory and metabolic markers released from adipose tissue (leptin, AFABP), nor anthropometric measures of adiposity or adipose tissue distribution (BMI, waist, WHtR) were identified as predictive factors of pregnancy or live birth rate.Trial registration: ClinicalTrials.gov number, NCT01566929. Trial registration date 30-03-2012, retrospectively registered.
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Patel N, Patel N, Pal S, Nathani N, Pandit R, Patel M, Patel N, Joshi C, Parekh B. Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility. BMC Womens Health 2022; 22:113. [PMID: 35413875 PMCID: PMC9004033 DOI: 10.1186/s12905-022-01681-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/22/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. METHODS We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). RESULT Compared with the controls, α-diversity and β-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. CONCLUSION The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.
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Affiliation(s)
- Nayna Patel
- Akanksha Hospital and Research Institute, Lambhvel Road, Lambhvel, Anand, Gujarat, 387310, India
| | - Nidhi Patel
- Gujarat Biotechnology Research Centre (GBRC), Gandhinagar, Gujarat, 382011, India
| | - Sejal Pal
- Akanksha Hospital and Research Institute, Lambhvel Road, Lambhvel, Anand, Gujarat, 387310, India
| | - Neelam Nathani
- Gujarat Biotechnology Research Centre (GBRC), Gandhinagar, Gujarat, 382011, India.,School of Applied Sciences & Technology (SAST-GTU), Gujarat Technological University, Visat - Gandhinagar Road, Chandkheda, Ahmedabad, Gujarat, 382424, India
| | - Ramesh Pandit
- Gujarat Biotechnology Research Centre (GBRC), Gandhinagar, Gujarat, 382011, India
| | - Molina Patel
- Akanksha Hospital and Research Institute, Lambhvel Road, Lambhvel, Anand, Gujarat, 387310, India
| | - Niket Patel
- Akanksha Hospital and Research Institute, Lambhvel Road, Lambhvel, Anand, Gujarat, 387310, India
| | - Chaitanya Joshi
- Gujarat Biotechnology Research Centre (GBRC), Gandhinagar, Gujarat, 382011, India
| | - Bhavin Parekh
- Akanksha Hospital and Research Institute, Lambhvel Road, Lambhvel, Anand, Gujarat, 387310, India.
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Zheng Y, Pan Y, Li P, Wang Z, Wang Z, Shi Y. Ovarian Sensitivity Decreased Significantly in Patients With Insulin Resistance Undergoing in vitro Fertilization and Embryo Transfer. Front Physiol 2022; 12:809419. [PMID: 35360506 PMCID: PMC8963761 DOI: 10.3389/fphys.2021.809419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 12/13/2021] [Indexed: 01/01/2023] Open
Abstract
Ovarian sensitivity could affect the outcome of in vitro fertilization and embryo transfer (IVF-ET). The objective of this study was to explore the relationship between the ovarian sensitivity index (OSI) and traditional ovarian response makers and observe the relationship between OSI and insulin resistance (IR). The patients enrolled in this study included 131 patients with polycystic ovary syndrome (PCOS) with IR (PCOS-IR), 52 patients with PCOS without IR (PCOS-N), 164 patients with control with IR (control-IR), 133 patients with control without IR (control-N), 295 patients with IR, 184 patients with non-IR, 183 patients with PCOS, and 297 patients with control (patients with non-PCOS). All patients received standard long protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol to induce follicular development. The two protocols downregulated the pituitary function or blocked the pituitary luteinizing hormone (LH) secretion with a GnRH antagonist. Both protocols can block premature LH surges because premature luteinization is not conducive to follicular development. All patients underwent IVF or intracytoplasmic sperm injection (ICSI). Embryo transfer was carried out according to the specific situation of each patient. The OSI was significantly reduced in patients with IR. The OSI had a significant positive relationship with anti-Müllerian hormone (AMH), antral follicle count (AFC), basal LH/follicle-stimulating hormone (FSH), dominant follicle number on trigger day, retrieved oocytes, embryo number, and high-quality embryo number. OSI had a significant negative relationship with age, body mass index (BMI), basal FSH, initial dose of Gn, and total dose of Gn. The receiver operating characteristic (ROC) curve of OSI demonstrated a better accuracy in distinguishing patients with positive pregnancy and clinical pregnancy, with an area under the curve (AUC) of 0.662 (95% CI, 0.598–0.727) and 0.636 (95% CI, 0.577–0.695), respectively. Patients could get a higher rate of dominant follicle count (p < 0.0001) through the treatment of standard long protocol when compared with GnRH antagonist protocol. The OSI has a significant correlation with traditional ovarian response markers and could be a good predictor of positive pregnancy and clinical pregnancy for patients with IR.
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Affiliation(s)
- Yanjun Zheng
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Shandong Key Laboratory of Reproductive Medicine, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
| | - Ye Pan
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Shandong Key Laboratory of Reproductive Medicine, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
| | - Ping Li
- Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Zhongyuan Wang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
| | - Ze Wang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Shandong Key Laboratory of Reproductive Medicine, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
| | - Yuhua Shi
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Yuhua Shi,
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Wang C, Wen YX, Mai QY. Impact of metabolic disorders on endometrial receptivity in patients with polycystic ovary syndrome. Exp Ther Med 2022; 23:221. [PMID: 35222698 DOI: 10.3892/etm.2022.11145] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022] Open
Abstract
The present study investigated the expression of endometrial receptivity-related molecules in patients with polycystic ovary syndrome (PCOS) and different androgen status, insulin resistance (IR) levels, and body mass indexes (BMI) to identify the mechanism underlying their effects on pregnancy outcomes. The present study recruited 43 participants from November 2020 to January 2021, which were classified into five groups: i) Hyperandrogenemia (HA) combined with impaired glucose tolerance group (n=8); ii) HA combined with diabetes mellitus group (n=8); iii) HA combined with non-IR (NIR) group (n=10); iv) non-HA (NHA) androgen combined with IR group (n=8); and v) NHA combined with NIR group (n=9). In addition, according to their BMIs, patients were sub-grouped into lean/normal (n=27), overweight (n=8) or obese (n=8) groups. The mRNA expression levels of endometrial receptivity-related molecules were detected using reverse transcription-quantitative PCR. In addition, flow cytometry was used to determine the phenotype and percentage of uterine natural killer cells (uNK). According to the results, patients with PCOS and IR status, HA and obesity (BMI ≥24 kg/m2) demonstrated significantly decreased mRNA expression levels of adiponectin, adiponectin receptor (AdipoR)1, AdipoR2, adapter protein containing PH domain, PTB domain and leucine zipper motif 1, estrogen receptor (ER) α, ERβ, progesterone receptor (PR), IL-15, integrin β3 avβ3, and insulin-like growth factor binding protein-1, but increased mRNA expression levels of IL-6 and IL-8 compared with NHA + NIR group or lean/normal group, respectively. In addition, obese patients with PCOS demonstrated increased mRNA expression levels of PR compared with overweight patients. This suggested that insulin resistant status, HA, and obesity could alter the endometrial receptivity of patients with PCOS, which may explain poorer embryo implantation and pregnancy outcomes in clinics.
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Affiliation(s)
- Can Wang
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
| | - Yang-Xing Wen
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
| | - Qing-Yun Mai
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China
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Pathare ADS, Hinduja I, Mahadik RC. Basic aspects of endometrial receptivity in PCOS patients. Mol Biol Rep 2022; 49:1519-1528. [PMID: 34988892 DOI: 10.1007/s11033-021-06976-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 11/17/2021] [Indexed: 12/12/2022]
Abstract
Polycystic Ovarian Syndrome (PCOS) is an endocrine disorder commonly affecting the reproductive capacity of women leading to infertility. PCOS-related infertility is majorly due to anovulation; however, it is not the only cause. The defective endometrium causing recurrent miscarriage and implantation failure can also be accountable for infertility in PCOS women. The unusual levels of hormones and their receptors in the PCOS endometrium have a hostile effect during WOI, making the microenvironment unfavorable for embryo implantation. To date, many studies have been performed to determine the role of candidate genes in endometrial receptivity but very limited data is available using whole genome approach. This review aims at summarizing the existing studies on the basic aspects of endometrial receptivity in PCOS. The review focuses on aberrant levels of hormones and their receptors in the endometrium, affecting the receptivity. Additionally, it explores the novel approach reviewing the effect on treatment options administered for ovulation induction in PCOS on their endometrial receptivity. Overall, this review will help us to understand the molecular milieu in PCOS endometrium and its effect on the receptivity potential. However, to have a thorough understanding of the mechanistic approach of hormonal imbalance in PCOS on endometrial receptivity, there is a need to give more weightage to genome-wide studies in the future. The current review will further guide us to formulate future studies using whole genome technologies for the assessment of endometrial receptivity in different cohorts of PCOS women, which may have future diagnostic implementations.
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Affiliation(s)
- Amruta D S Pathare
- Department of IVF and Research, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, 400016, India
| | - Indira Hinduja
- Department of IVF and Research, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, 400016, India.
| | - Roshani C Mahadik
- Department of IVF and Research, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, 400016, India
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Ramanjaneya M, Diboun I, Rizwana N, Dajani Y, Ahmed L, Butler AE, Almarzooqi TA, Shahata M, Al Bader MK, Elgassim E, Burjaq H, Atkin SL, Abou-Samra AB, Elrayess MA. Elevated Adipsin and Reduced C5a Levels in the Maternal Serum and Follicular Fluid During Implantation Are Associated With Successful Pregnancy in Obese Women. Front Endocrinol (Lausanne) 2022; 13:918320. [PMID: 35909516 PMCID: PMC9326155 DOI: 10.3389/fendo.2022.918320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Complement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women. METHODS Forty overweight/obese (BMI = 30.8 ± 5.2 kg/m2) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models. RESULTS Out of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF (p = 0.01) but lower C5a levels (p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D (R = 0.5, p = 0.02), glucagon (R = 0.4, p = 0.03), leptin (R = 0.4, p = 0.01), resistin (R = 0.4, p = 0.02), and visfatin (R = 0.4, p = 0.02), but negatively correlated with total protein (R = -0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels (p ≤ 0.01). CONCLUSIONS Higher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies.
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Affiliation(s)
- Manjunath Ramanjaneya
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | | | - Najeha Rizwana
- Biomedical Research Center (BRC), Qatar University, Doha, Qatar
| | | | | | | | - Thoraya Ali Almarzooqi
- Obstetrics and Gynecology Department, Women’s Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Mohammed Shahata
- Obstetrics and Gynecology Department, Women’s Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Moza Khalaf Al Bader
- Obstetrics and Gynecology Department, Women’s Hospital, Hamad Medical Corporation, Doha, Qatar
| | | | - Hasan Burjaq
- Obstetrics and Gynecology Department, Women’s Hospital, Hamad Medical Corporation, Doha, Qatar
| | | | | | - Mohamed A. Elrayess
- Biomedical Research Center (BRC), Qatar University, Doha, Qatar
- QU Health, Qatar University, Doha, Qatar
- *Correspondence: Mohamed A. Elrayess,
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22
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Abstract
OBJECTIVE To determine the cutoff values of HOMA-IR for predicting clinical pregnancy rate in normal weight patients during their first IVF. MATERIALS AND METHODS The data was retrospectively analyzed from 329 normal-weight women aged 21-40 years with BMI <25 kg/m2 who received first IVF-ET during the period from December 2018 to June 2019.We assessed the associations between HOMA-IR and clinical pregnancy rates during IVF in the women with or without PCOS according to different BMI ranges. RESULTS In non PCOS,clinical pregnancy rate was significantly decreased at the HOMA-IR values ranging from 2.2 to 3.15 (OR, 0.188, 95% CI, 0.084-0.42; p < .05) and at those >3.15 (OR, 0.018, 95% CI, 0.004-0.081; p < .05).In PCOS, clinical pregnancy rate significantly decreased at the HOMA-IR >3.15 (OR, 0.15, 95% CI, 0.044-0.507; p < .05). In non PCOS with BMI <21.45 kg/m2, clinical pregnancy rate was decreased with HOMA-IR >2.2, and a significant cutoff point at HOMA-IR >3.15; with 21.45 ≤ BMI <25 kg/m2, clinical pregnancy rate was declined significantly at the HOMA-IR >1.56 (OR, 0.196, 95% CI, 0.055-0.704).In PCOS with BMI <21.45 kg/m2, clinical pregnancy rate was decreased as the HOMA-IR increased, but there was no significant cutoff point; with 21.45 ≤ BMI < 25 kg/m2, clinical pregnancy rate was declined significantly at the HOMA-IR > 3.15 (OR, 0.186; 95% CI, 0.04-0.872). CONCLUSION HOMA-IR and BMI had adverse effects on the IVF outcome of infertility women. Moreover, obesity can increase the degree of insulin resistance in infertility women. These findings suggested that only better HOMA-IR and BMI will lead to better IVF results.
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Affiliation(s)
- Haixia Song
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Reproductive Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
| | - Zhenqing Yu
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
| | - Ping Li
- Women and Children's Hospital Affiliated to Xiamen University, Xiamen, China
| | - Ying Wang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
| | - Yuhua Shi
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China
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Liu T, Liu D, Song X, Qu J, Zheng X, Li J, Yang R, Yang S, Zhang X, Wang H, Yan L, Ma C, Li R, Yan J, Qiao J. Lipid Metabolism Was Associated With Oocyte in vitro Maturation in Women With Polycystic Ovarian Syndrome Undergoing Unstimulated Natural Cycle. Front Cell Dev Biol 2021; 9:719173. [PMID: 34540838 PMCID: PMC8446356 DOI: 10.3389/fcell.2021.719173] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/09/2021] [Indexed: 11/13/2022] Open
Abstract
Objective Hyperlipidemia are common polycystic ovarian syndrome (PCOS)-related metabolic dysfunctions and can adversely affect assisted reproductive technology (ART) outcomes in controlled ovarian hyperstimulation (COH) cycles. The objective of this study is to analyze the relationship between lipid metabolism and ART outcomes in unstimulated natural cycles without the utilization of ovarian induction drugs, which is still uncertain. Methods This retrospective study included infertile women with PCOS between 21 and 40 years old undergoing unstimulated natural cycles from January 01, 2006 to December 31, 2019. Lipid metabolism was measured by body mass index (BMI) and serum biochemical parameters including total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C). ART outcomes were measured by number of oocytes retrieved, oocyte maturation quality and developmental potential, clinical pregnancy and live birth. Results A total of 586 patients were included in this study. Multivariate Poisson log-linear analysis showed that high TC (≥5.18 mmol/L), triglycerides (TG) (≥1.76 mmol/L), LDL-C (≥3.37 mmol/L) levelsand low HDL-C levels (≤1.04 mmol/L) were significantly (PTC = 0.001, PTG < 0.001, PHDL–C < 0.001, PLDL–C < 0.001) associated with increased number of oocytes retrieved. BMI was significantly negatively associated with maturation rate (P < 0.001), fertilization rate (P < 0.001) and transferrable embryo rate (P = 0.002). High TG levels and low HDL-C levels were also associated with decreased maturation rate (PTG < 0.001, PHDL–C = 0.026). Logistic regression analysis showed statistically significant association between obesity (≥28.0 kg/m2) and decreased live birth rate (P = 0.004) as well as cumulative live birth rate (P = 0.007). Conclusion This is the first study that focused on the relationship between basal lipid metabolism and ART outcomes in women with PCOS undergoing unstimulated natural cycles. The results showed that high levels of lipid metabolic parameters were associated with increased number of oocytes retrieved and obesity was closely associated with impaired oocyte maturation quality and developmental potential as well as poor live birth outcomes.
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Affiliation(s)
- Tao Liu
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Dongming Liu
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Xueling Song
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Jiangxue Qu
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoying Zheng
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Jia Li
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Rui Yang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Shuo Yang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Xi Zhang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Haiyan Wang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Liying Yan
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Caihong Ma
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Rong Li
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Jie Yan
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
| | - Jie Qiao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.,National Clinical Research Center for Obstetrics and Gynecology, Beijing, China.,Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing, China.,Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing, China.,Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, China
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Bai X, Zheng L, Li D, Xu Y. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review. Reprod Biol Endocrinol 2021; 19:122. [PMID: 34362377 PMCID: PMC8344130 DOI: 10.1186/s12958-021-00802-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 07/12/2021] [Indexed: 12/14/2022] Open
Abstract
Polycystic ovary syndrome (PCOS) is a neuroendocrine heterogeneous disease that frequently occurs in women of reproductive age, causing serious damage to the fertility, quality of life, and physical and mental health of patients. The current studies have proved that satisfactory endometrial receptivity is one of the conditions that must be met during the process of spermatovum position, adhesion and invasion, as well as the subsequent blastocyst division and embryo development. Women with PCOS may suffer a series of pathological processes such as changes in the expression levels of hormones and related receptors, imbalances in the proportion of miscellaneous cytokines, insulin resistance, low-grade chronic inflammation and endometrial morphological changes, which will damage endometrial receptivity from various aspects and obstruct fertilized egg nidation and embryonic development, thus causing adverse reproductive health events including infertility and abortion. This article reviews the research progress about characteristics and related influencing factors of endometrial receptivity in PCOS patients.
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Affiliation(s)
- Xuechun Bai
- The Second Hospital of Jilin University, Jilin Province Changchun City, China
| | - Lianwen Zheng
- The Second Hospital of Jilin University, Jilin Province Changchun City, China
| | - Dandan Li
- The Second Hospital of Jilin University, Jilin Province Changchun City, China
| | - Ying Xu
- The Second Hospital of Jilin University, Jilin Province Changchun City, China
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25
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Jiang NX, Li XL. The Disorders of Endometrial Receptivity in PCOS and Its Mechanisms. Reprod Sci 2021; 29:2465-2476. [PMID: 34046867 DOI: 10.1007/s43032-021-00629-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 05/19/2021] [Indexed: 12/14/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a mysterious and complicated endocrine disease with the combination of metabolic, reproductive, psychological dysfunctions. Impaired endometrial receptivity and ovulation disorders/anovulation are both important causes of PCOS-related infertility. However, change in endometrium has never received the same attention as ovulatory dysfunction. Besides, putting emphasis on endometrial function may be more realistic for PCOS-related infertility, given the wide use of assisted reproductive technology. The present review focuses on the disorders of endometrial receptivity of patients with PCOS, summarizes the changes of the indicators of endometrial receptivity including leukemia inhibitory factor, homeobox genes A, pinopodes, αvβ3-integrin, and intercellular junctions and also analyzes the possible mechanisms of decreased endometrial receptivity and its relationship with the main endocrine and metabolic disorders of PCOS such as hyperandrogenism, inflammation, insulin resistance, and obesity. Despite several biomarkers have been found to be associated with decreased endometrial receptivity in PCOS, the clinical relevance of these findings still awaits future clarification.
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Affiliation(s)
- Nan-Xing Jiang
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China
| | - Xue-Lian Li
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China. .,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People's Republic of China.
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26
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Luo Y, Cui C, Han X, Wang Q, Zhang C. The role of miRNAs in polycystic ovary syndrome with insulin resistance. J Assist Reprod Genet 2021; 38:289-304. [PMID: 33405004 PMCID: PMC7884539 DOI: 10.1007/s10815-020-02019-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/22/2020] [Indexed: 02/07/2023] Open
Abstract
PURPOSE This review aims to summarize the key findings of several miRNAs and their roles in polycystic ovary syndrome with insulin resistance, characterize the disease pathogenesis, and establish a new theoretical basis for diagnosing, treating, and preventing polycystic ovary syndrome. METHODS Relevant scientific literature was covered from 1992 to 2020 by searching the PubMed database with search terms: insulin/insulin resistance, polycystic ovary syndrome, microRNAs, and metabolic diseases. References of relevant studies were cross-checked. RESULTS The related miRNAs (including differentially expressed miRNAs) and their roles in pathogenesis, and possible therapeutic targets and pathways, are discussed, highlighting controversies and offering thoughts for future directions. CONCLUSION We found abundant evidence on the role of differentially expressed miRNAs with its related phenotypes in PCOS. Considering the essential role of insulin resistance in the pathogenesis of PCOS, the alterations of associated miRNAs need more research attention. We speculate that race/ethnicity or PCOS phenotype and differences in methodological differences might lead to inconsistencies in research findings; thus, several miRNA profiles need to be investigated further to qualify for the potential therapeutic targets for PCOS-IR.
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Affiliation(s)
- Yingliu Luo
- Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan Province, People's Republic of China
| | - Chenchen Cui
- Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan Province, People's Republic of China
- Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou, 450003, Henan Province, People's Republic of China
| | - Xiao Han
- Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan Province, People's Republic of China
| | - Qian Wang
- Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan Province, People's Republic of China
- Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou, 450003, Henan Province, People's Republic of China
| | - Cuilian Zhang
- Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan Province, People's Republic of China.
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27
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Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum Reprod Update 2020; 27:584-618. [PMID: 33302299 DOI: 10.1093/humupd/dmaa051] [Citation(s) in RCA: 198] [Impact Index Per Article: 39.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/29/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute to subfertility and poor reproductive outcomes in affected women. OBJECTIVE AND RATIONALE The aim of this review was to determine whether there is sufficient evidence to support that endometrial function is altered in women with PCOS, whether clinical features of PCOS affect the endometrium, and whether there are evidence-based interventions to improve endometrial dysfunction in PCOS women. SEARCH METHODS An extensive literature search was performed from 1970 up to July 2020 using PubMed and Web of Science without language restriction. The search included all titles and abstracts assessing a relationship between PCOS and endometrial function, the role played by clinical and biochemical/hormonal factors related to PCOS and endometrial function, and the potential interventions aimed to improve endometrial function in women with PCOS. All published papers were included if considered relevant. Studies having a specific topic/hypothesis regarding endometrial cancer/hyperplasia in women with PCOS were excluded from the analysis. OUTCOMES Experimental and clinical data suggest that the endometrium differs in women with PCOS when compared to healthy controls. Clinical characteristics related to the syndrome, alone and/or in combination, may contribute to dysregulation of endometrial expression of sex hormone receptors and co-receptors, increase endometrial insulin-resistance with impaired glucose transport and utilization, and result in chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities in women with PCOS. Among several interventions to improve endometrial function in women with PCOS, to date, only lifestyle modification, metformin and bariatric surgery have the highest scientific evidence for clinical benefit. WIDER IMPLICATIONS Endometrial dysfunction and abnormal trophoblast invasion and placentation in PCOS women can predispose to miscarriage and pregnancy complications. Thus, patients and their health care providers should advise about these risks. Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.
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Affiliation(s)
- Stefano Palomba
- Unit of Obstetrics and Gynecology, Grande Ospedale Metropolitano of Reggio Calabria, Reggio Calabria, Italy
| | - Terhi T Piltonen
- Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
| | - Linda C Giudice
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA
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Sun YF, Zhang J, Xu YM, Cao ZY, Wang YZ, Hao GM, Gao BL. High BMI and Insulin Resistance Are Risk Factors for Spontaneous Abortion in Patients With Polycystic Ovary Syndrome Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 2020; 11:592495. [PMID: 33343510 PMCID: PMC7744738 DOI: 10.3389/fendo.2020.592495] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/05/2020] [Indexed: 12/17/2022] Open
Abstract
Background The risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle. Methods A systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity. Results Among 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [0.29, 0.44], MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR = 0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]). Conclusion High BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.
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Affiliation(s)
| | | | | | | | | | - Gui-Min Hao
- Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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29
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Effect of Three Androgen Indexes (FAI, FT, and TT) on Clinical, Biochemical, and Fertility Outcomes in Women with Polycystic Ovary Syndrome. Reprod Sci 2020; 28:775-784. [PMID: 32989632 DOI: 10.1007/s43032-020-00316-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/10/2020] [Indexed: 10/23/2022]
Abstract
This work sought to evaluate the effects of three androgen indexes of free testosterone (FT), total testosterone (TT), and free-androgen index (FAI) on clinical phenotype, endocrine metabolic disorders, and fertility outcomes in women with polycystic ovary syndrome. The data in this study came from a large, multicenter, randomized double-blind controlled clinical trial involving 1000 infertile PCOS patients. Baseline phenotypic, endocrine, and metabolic parameters and fertility outcomes undergoing ovulation induction were collected. FAI is superior to FT, and FT is superior to TT in terms of their correlation with anthropometric parameters and metabolic profile. FT and TT were significantly positively correlated with LH/FSH. FAI and FT were significantly correlated with the incidence of metabolic syndrome. FAI, FT, and TT were significantly positively correlated with polycystic ovary morphology and menstrual period. FAI was significantly related ovulations per cycle, pregnancy, conception, and live birth rates. After adjusting for age, the increased FT level was significantly related to the decreased rates of ovulations per cycle, conception, and pregnancy. FAI is superior to FT and FT is superior to TT in terms of their correlation with phenotypic and metabolic parameters in PCOS patients. FAI and FT are important factors related to the fertility outcomes of infertile PCOS patients. Clinical trial registration number: NCT01573858.
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30
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He FF, Li YM. Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review. J Ovarian Res 2020; 13:73. [PMID: 32552864 PMCID: PMC7301991 DOI: 10.1186/s13048-020-00670-3] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 06/01/2020] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder. Typically, it is characterized by hirsutism, hyperandrogenism, ovulatory dysfunction, menstrual disorders and infertility. To date, its pathogenesis remains unclear. However, insulin resistance (IR) is considered as the primary pathological basis for its reproductive dysfunction. On the other hand, a condition in which insulin is over-secreted is called hyperinsulinemia. IR/Hyperinsulinemia is associated with chronic inflammation, hormonal changes, follicular dysplasia, endometrial receptivity changes, and abortion or infertility. Additionally, it increases incidence of complications during pregnancy and has been associated with anxiety, depression, and other psychological disorders. Gut microbiota, the "second genome" acquired by the human body, can promote metabolism, immune response through interaction with the external environment. Gut microbiota dysbiosis can cause IR, which is closely linked to the occurrence of PCOS. This article reviewed recent findings on the roles of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome.
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Affiliation(s)
- Fang-Fang He
- Department of Assisted Reproduction, Xiangya Hospital affiliated Central South University, Changsha, 410008, People's Republic of China
| | - Yu-Mei Li
- Department of Assisted Reproduction, Xiangya Hospital affiliated Central South University, Changsha, 410008, People's Republic of China.
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31
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Sun Q, Yang Y, Peng X, Zhang Y, Gao Y, Wang F, Zhang Y, Feng W, Yang W, Kang X. Coagulation parameters predictive of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2019; 240:36-40. [PMID: 31226575 DOI: 10.1016/j.ejogrb.2019.06.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 06/06/2019] [Accepted: 06/12/2019] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To explore coagulation parameters in association with polycystic ovarian syndrome (PCOS) and establish a model for predicting the risk of PCOS. STUDY DESIGN This study included 181 outpatients with PCOS. A total of 301 women who attempted to seek pre-pregnancy consultation at the Department of Gynecology of our hospital were included in the control group, and six coagulation parameters were measured for all included subjects. A logistic regression model was built based on the training dataset using the purposeful selection method to select important predictors. The performance of the established model was validated on the test dataset. RESULTS There were statistically significant differences found among all coagulation parameters except D-Dimer (DD, P = 0.080). The purposeful selection method selected age (odds ratio [OR] = 0.89; p = 0.008), prothrombin time (PT, OR = 0.68, p < 0.0001), thrombin time (TT, OR = 3.30; p = 0.0005), and fibrin degradation products (FDP, OR = 0.24; p = 0.0002) as important predictors of PCOS risk. The receiver operating characteristic (ROC) curve analysis indicated that the area under the ROC curve (AUC) of the model was 0.81 for the training dataset with an optimal cut-off point of the predicted probability of 0.45, leading to a sensitivity of 0.71 and a specificity of 0.82. The AUC was 0.79 for the test data. CONCLUSIONS It was found that the coagulation parameters, including PT, TT, and FDP, are predictive of PCOS. These results highlight the potential of anti-coagulation therapies to lower the risk of adverse outcomes in women with PCOS.
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Affiliation(s)
- Qian Sun
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Yan Yang
- Department of Laboratory, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Xuenan Peng
- Department of Clinical Medicine, Medical College of Soochow University, Soochow, Jiangsu, China
| | - Yunyan Zhang
- Department of Laboratory, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Yuan Gao
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Fang Wang
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Yang Zhang
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Wen Feng
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China
| | - Wen Yang
- Department of Gynecology, The First People's Hospital of Lianyungang, Lianyung, Jiangsu, China.
| | - Xiaomin Kang
- Department of Reproductive Medical Centre, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
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Bishop CV, Stouffer RL, Takahashi DL, Mishler EC, Wilcox MC, Slayden OD, True CA. Chronic hyperandrogenemia and western-style diet beginning at puberty reduces fertility and increases metabolic dysfunction during pregnancy in young adult, female macaques. Hum Reprod 2019; 33:694-705. [PMID: 29401269 DOI: 10.1093/humrep/dey013] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 01/12/2018] [Indexed: 02/02/2023] Open
Abstract
STUDY QUESTION What are the impacts of elevated testosterone (T) and an obesogenic western-style diet (WSD), either independently or together, on fertility and metabolic adaptations of pregnancy in primates? SUMMARY ANSWER Testosterone increases the time to achieve pregnancy, while a WSD reduces overall fertility, and the combination of testosterone and WSD additionally impairs glucose tolerance and causes pregnancy loss. WHAT IS KNOWN ALREADY Both hyperandrogenemia and obesity are hallmarks of polycystic ovary syndrome, which is a leading cause of infertility among women worldwide. Female macaques receiving T and WSD beginning at puberty show increased metabolic, ovarian and uterine dysfunction in the non-pregnant state by 3 years of treatment. STUDY DESIGN, SIZE, DURATION The same cohort of female rhesus macaques continued treatments from the time of puberty (2.5 years) to 4 years, including this fertility trial. There were four groups (n = 9-10/group): controls (C), T-treated (T; average total serum level 1.35 ng/ml), WSD-treated, and combined T and WSD-treated (T + WSD) females. PARTICIPANTS/MATERIALS, SETTING, METHODS Females, which were typically having menstrual cycles, were paired for 4 days with a proven male breeder following the late follicular rise in circulating estradiol (≥100 pg/ml). The presence of sperm in the reproductive tract was used to confirm mating. Animals went through up to three successive rounds of mating until they became pregnant, as confirmed by a rise in circulating mCG during the late luteal phase and ultrasound evidence of a gestational sac at Day 30 post-mating (GD30). Placental vascular parameters were also measured at GD30. Metabolic measurements consisted of fasting levels of blood glucose and insulin at approximately GD30, 60, 90 and 115, as well as an intravenous (iv) glucose tolerance test (GTT) at GD115. MAIN RESULTS AND THE ROLE OF CHANCE While all animals in the C and T groups eventually became pregnant, T-treated females on average had a greater interval to achieve pregnancy (P < 0.05). However, only ~70% of animals in the WSD and T + WSD groups became pregnant (P < 0.004). One pregnancy in T + WSD group resulted in an anembryonic pregnancy which miscarried around GD60, while another T + WSD female conceived with a rare identical twin pregnancy which required cessation due to impending fetal loss at GD106. Thus, the number of viable fetuses was less in the T + WSD group, compared to C, T or WSD. Placental blood volume at GD30 was reduced in all treatments compared to the C group (P < 0.05). Maternal P4 levels were elevated in the WSD (P < 0.03) group and E2 levels were elevated in T + WSD animals (P < 0.05). An increase in serum A4 levels throughout gestation was observed in all groups (P < 0.03) except WSD (P = 0.3). All groups displayed increased insulin resistance with pregnancy, as measured from the ivGTT during pregnancy. However, only the T + WSD group had a significant increase in fasting glucose levels and glucose clearance during the GTT indicating a worsened glucose tolerance. WSD treatment decreased female fetuses third trimester weights, but there was an interaction between WSD and T to increase female fetal weight when normalized to maternal weight. LARGE SCALE DATA N/A. LIMITATIONS REASONS FOR CAUTION The small number of pregnancies in the WSD and T + WSD groups hampers the ability to make definitive conclusions on effects during gestation. Also, the high fertility rate in the controls indicates the cohort was at their breeding prime age, which may impair the ability to observe subtle fertility defects. The low number of fetuses used for male and female analysis requires additional studies. WIDER IMPLICATIONS OF THE FINDINGS The current findings strongly suggest that both hyperandrogenemia and obesity have detrimental effects on fertility and gestation in primates, which may be directly relevant to women with polycystic ovary syndrome. STUDY FUNDING/COMPETING INTEREST(S) All ONPRC Cores and Units were supported by NIH Grant P51 OD011092 awarded to ONPRC. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) of the National Institutes of Health (NIH) under Award Number P50HD071836 (to R.L.S.). The authors have no competing conflict of interests to disclose.
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Affiliation(s)
- C V Bishop
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - R L Stouffer
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - D L Takahashi
- Cardiometabolic Health Division, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - E C Mishler
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - M C Wilcox
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - O D Slayden
- Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
| | - C A True
- Cardiometabolic Health Division, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Ave, Beaverton, OR 97006, USA
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Qi J, Wang W, Zhu Q, He Y, Lu Y, Wang Y, Li X, Chen ZJ, Sun Y. Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2018; 103:2457-2467. [PMID: 29618067 DOI: 10.1210/jc.2017-02459] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 03/26/2018] [Indexed: 12/22/2022]
Abstract
CONTEXT Endometrial insulin resistance (IR) may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated. OBJECTIVE To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 1 and 2 and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial IR and local cortisol. DESIGN We measured cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on the seventh day after human chorionic gonadotropin injection. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs). RESULTS The cortisol concentration was elevated, whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared with those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN). CONCLUSIONS Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.
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Affiliation(s)
- Jia Qi
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Wangsheng Wang
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Qinling Zhu
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Yaqiong He
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Yao Lu
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Yuan Wang
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Xiaoxue Li
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
| | - Zi-Jiang Chen
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China
| | - Yun Sun
- Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
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Julania S, Walls ML, Hart R. The Place of In Vitro Maturation in PCO/PCOS. Int J Endocrinol 2018; 2018:5750298. [PMID: 30154841 PMCID: PMC6091445 DOI: 10.1155/2018/5750298] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 02/13/2018] [Accepted: 07/03/2018] [Indexed: 11/29/2022] Open
Abstract
In vitro maturation (IVM) of human oocytes is an emerging treatment option for women with polycystic ovary/polycystic ovary syndrome (PCO/PCOS) in addition to the standard in vitro fertilization (IVF) treatment. There has been significant improvements in pregnancy rates with IVM over the last two decades. This article reviews the place of IVM for women with PCO/PCOS, placing an emphasis on the predictors of successful pregnancy, optimization of culture media, IVM protocols, pregnancy rates, and neonatal outcomes following IVM treatment.
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Affiliation(s)
- Shital Julania
- King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia
| | - Melanie L. Walls
- Fertility North, Suite 213, Specialist Medical Centre, Joondalup Health Campus, Shenton Avenue, Joondalup, WA 6027, Australia
- Fertility Specialists of Western Australia, Bethesda Hospital, 25 Queenslea Drive, Claremont, Perth, WA 6010, Australia
| | - Roger Hart
- Fertility Specialists of Western Australia, Bethesda Hospital, 25 Queenslea Drive, Claremont, Perth, WA 6010, Australia
- Division of Obstetrics and Gynaecology, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Perth, WA 6008, Australia
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Cakiroglu Y, Doger E, Vural F, Kopuk SY, Vural B. Impact of insulin resistance and obesity on intracytoplasmic sperm injection outcomes in young women with polycystıc ovary syndrome. North Clin Istanb 2017; 4:218-224. [PMID: 29270569 PMCID: PMC5724915 DOI: 10.14744/nci.2017.79663] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 07/06/2017] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE To examine effects of body mass index (BMI) and insulin resistance (IR) on the in vitro fertilization (IVF) outcomes in women with polycystic ovary syndrome (PCOS). METHODS A total of 106 women with PCOS who underwent intracytoplasmic sperm injection were investigated. The patients were stratified into groups according to their BMI [healthy weight: BMI <25 kg/m2 (n=51), overweight: ≤25-29.9 kg/m2 (n=27), and obese: ≥30 kg/m2 (n=28)]. Secondly, the patients were classified based on the presence of IR (IR was considered to be present if homeostatic model assessment-IR was >2.5). The main outcome measures were reproductive and IVF outcomes with respect to BMI and IR. RESULTS The basal hormonal evaluations, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, estradiol, testosterone, DHEAS, AMH, and antral follicle counts, were similar between the groups of BMI and IR. The number of retrieved oocytes, MII oocytes, embryo counts, and fertilization and pregnancy rates were similar between lean and overweight/obese PCOS with and without IR. Even though pregnancy and delivery rates per started cycle and embryo transfer were higher in healthy-weight women with PCOS than in overweight/obese patients, it did not reach statistical significance. CONCLUSION Reproductive outcomes in women with PCOS according to BMI and IR were similar. Neither BMI nor IR had an independent effect on ovarian response and IVF success in young women with PCOS.
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Affiliation(s)
- Yigit Cakiroglu
- Department of Obstetrics and Gynecology, Kocaeli University, Kocaeli, Turkey
| | - Emek Doger
- Department of Obstetrics and Gynecology, Kocaeli University, Kocaeli, Turkey
| | - Fisun Vural
- Department of Obstetrics and Gynecology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey
| | - Sule Yildirim Kopuk
- Department of Obstetrics and Gynecology, Health Science University, Umraniye Education and Research Hospital, Istanbul, Turkey
| | - Birol Vural
- Department of Obstetrics and Gynecology, Kocaeli University, Kocaeli, Turkey
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Wei D, Zhang B, Shi Y, Zhang L, Zhao S, Du Y, Xu L, Legro RS, Zhang H, Chen ZJ. Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2017; 102:3822-3829. [PMID: 28938429 DOI: 10.1210/jc.2017-01294] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 08/09/2017] [Indexed: 12/30/2022]
Abstract
CONTEXT Women with polycystic ovary syndrome (PCOS) commonly have intrinsic insulin resistance and are recommended to undergo an oral glucose tolerance test (OGTT) for diabetes screening. However, the effect of preconception impaired glucose tolerance (IGT) on pregnancy is still unclear. OBJECTIVE To prospectively assess the effect of preconception IGT on pregnancy outcomes. DESIGN, SETTING, PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES This was a secondary analysis of a multicenter randomized trial in 1508 women with PCOS comparing live birth and obstetric complications between fresh and frozen embryo transfer. At baseline, fasting and 2-hour glucose and insulin levels after 75-g OGTT were measured. RESULTS Women with preconception IGT had higher risks of gestational diabetes in both singleton pregnancy [9.5% vs 3.2%; odds ratio (OR) 3.13; 95% confidence interval (CI) 1.23to 7.69] and twin pregnancy (20.0% vs 3.2%; OR 7.69; 95% CI 2.78 to 20.00) than women with normoglycemia. Preconception IGT was associated with a higher risk of large for gestational age in singleton newborns compared with normoglycemia (34.7% vs 19.8%; OR 2.13; 95% CI 1.19 to 3.85) or isolated impaired fasting glucose (i-IFG) (34.7% vs 15.4%; OR 2.94; 95% CI 1.33 to 6.25). Women with preconception IGT had a higher singleton pregnancy loss rate than women with i-IFG (31.4% vs 17.5%; OR 2.17; 95% CI 1.11 to 4.17). After adjusting for age, body mass index, duration of infertility, total testosterone level, and treatment groups (frozen vs fresh embryo transfer), these associations remained. CONCLUSIONS Preconception IGT, independent from BMI, was associated with adverse pregnancy outcome compared with i-IFG and normoglycemia.
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Affiliation(s)
- Daimin Wei
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China
| | - Bo Zhang
- Center for Reproductive Medicine, Maternal and Child Health Hospital in Guangxi, Nanning 530003, China
| | - Yuhua Shi
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China
| | - Lin Zhang
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China
| | - Shigang Zhao
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China
| | - Yanzhi Du
- Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China
| | - Lizhen Xu
- Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200000, China
| | - Richard S Legro
- Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, Pennsylvania 17033
| | - Heping Zhang
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520
| | - Zi-Jiang Chen
- Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250001, China
- Key Laboratory of Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan 250001, China
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250001, China
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Evans J, Salamonsen LA, Winship A, Menkhorst E, Nie G, Gargett CE, Dimitriadis E. Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol 2016; 12:654-667. [PMID: 27448058 DOI: 10.1038/nrendo.2016.116] [Citation(s) in RCA: 217] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The human endometrium is a highly dynamic tissue that is cyclically shed, repaired, regenerated and remodelled, primarily under the orchestration of oestrogen and progesterone, in preparation for embryo implantation. Humans are among the very few species that menstruate and that, consequently, are equipped with unique cellular and molecular mechanisms controlling these cyclic processes. Many reproductive pathologies are specific to menstruating species, and studies in animal models rarely translate to humans. Abnormal remodelling and regeneration of the human endometrium leads to a range of reproductive complications. Furthermore, the processes regulating endometrial remodelling and implantation, including those controlling hormonal impact, breakdown and repair, stem/progenitor cell activation, inflammation and cell invasion have broad applications to other fields. This Review presents current knowledge regarding the normal and abnormal function of the human endometrium. The development of biomarkers for prediction of uterine diseases and pregnancy disorders and future avenues of investigation to improve fertility and enhance endometrial function are also discussed.
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Affiliation(s)
- Jemma Evans
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
- Department of Physiology, Monash University, Clayton, 3800, Australia
| | - Lois A Salamonsen
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, 3800, Australia
| | - Amy Winship
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
| | - Ellen Menkhorst
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
| | - Guiying Nie
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Australia
| | - Caroline E Gargett
- Department of Obstetrics and Gynaecology, Monash University, Clayton, 3800, Australia
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, 3168, Australia
| | - Eva Dimitriadis
- Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia
- Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia
- Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia
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Seok HH, Song H, Lyu SW, Kim YS, Lee DR, Lee WS, Yoon TK. Application of serum anti-Müllerian hormone levels in selecting patients with polycystic ovary syndrome for in vitro maturation treatment. Clin Exp Reprod Med 2016; 43:126-32. [PMID: 27358832 PMCID: PMC4925868 DOI: 10.5653/cerm.2016.43.2.126] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 02/22/2016] [Accepted: 02/26/2016] [Indexed: 11/06/2022] Open
Abstract
Objective The purpose of this study was to identify useful clinical factors for the identification of patients with polycystic ovary syndrome (PCOS) who would benefit from in vitro maturation (IVM) treatment without exhibiting compromised pregnancy outcomes. Methods A retrospective cohort study was performed of 186 consecutive patients with PCOS who underwent human chorionic gonadotropin-primed IVM treatment between March 2010 and March 2014. Only the first IVM cycle of each patient was included in this study. A retrospective case-control study was subsequently conducted to compare pregnancy outcomes between IVM and conventional in vitro fertilization (IVF) cycles. Results Through logistic regression analyses, we arrived at the novel finding that serum anti-Müllerian hormone (AMH) levels and the number of fertilized oocytes in IVM were independent predictive factors for live birth with unstandardized coefficients of 0.078 (95% confidence interval [CI], 1.005–1.164; p=0.037) and 0.113 (95% CI, 1.038–1.208; p=0.003), respectively. Furthermore, these two parameters were able to discriminate patients who experienced live births from non-pregnant IVM patients using cut-off levels of 8.5 ng/mL and five fertilized oocytes, respectively. A subsequent retrospective case-control study of patients with PCOS who had serum AMH levels ≥8.5 ng/mL showed that IVM had pregnancy outcomes comparable to conventional IVF, and that no cases of ovarian hyperstimulation syndrome were observed. Conclusion Serum AMH levels are a useful factor for predicting pregnancy outcomes in PCOS patients before the beginning of an IVM cycle. IVM may be an alternative to conventional IVF for PCOS patients if the patients are properly selected according to predictive factors such as serum AMH levels.
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Affiliation(s)
- Hyun Ha Seok
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Haengseok Song
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea.; Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Sang Woo Lyu
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - You Shin Kim
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Dong Ryul Lee
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea.; Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Woo Sik Lee
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Tae Ki Yoon
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
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Piltonen TT. Polycystic ovary syndrome: Endometrial markers. Best Pract Res Clin Obstet Gynaecol 2016; 37:66-79. [PMID: 27156350 DOI: 10.1016/j.bpobgyn.2016.03.008] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Accepted: 03/05/2016] [Indexed: 12/31/2022]
Abstract
Women with polycystic ovarian syndrome (PCOS) present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS and an increased miscarriage rate have been suggested to coincide, but the results are conflicting. Recent studies have also shown increased risks of pregnancy-induced hypertension, preeclampsia, and premature delivery that may be related to altered decidualization/placentation in affected women. In the long run, PCOS per se is associated with the occurrence of endometrial cancer (EC), with obesity aggravating the risk. Most investigated markers of the endometrial abnormalities in women with PCOS are related to steroid hormone action (ERs (estrogen receptors), PRs (progesterone receptors), ARs (androgen receptors), and steroid receptor coactivators), endometrial receptivity/decidualization (HOXA10, αvβ3 integrin, and IGFBP-1 (insulin-like growth factor-binding protein 1)), glucose metabolism (IRs (insulin receptors), glucose transporters, IGFs) and inflammation/immune cell migration ((IL-6 (interleukin 6), CCL2 (CC motif ligand), and uNK (uterine natural killer) cells). Despite several endometrial abnormalities in women with PCOS, the clinical relevance of these findings still awaits future clarification; to date, no common screening protocols/recommendations for women with PCOS have been established.
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Affiliation(s)
- Terhi T Piltonen
- Clinical Researcher for the Finnish Medical Foundation, Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Kajaanintie 50, BOX 5000, 90014 Oulu, Finland.
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Xu M, Tian YZ, Zhu XJ, Zhang X, Zhu JY, Gu CX, Chen Y, Huang JL. Effect of Xianziyizhen Recipe Capsule on PGI2-PPARδ Signaling Pathway in Embryo Implantation Dysfunction Mice. Am J Reprod Immunol 2015; 73:545-56. [PMID: 25648617 DOI: 10.1111/aji.12361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Accepted: 01/02/2015] [Indexed: 12/22/2022] Open
Abstract
PROBLEM We investigated the effect of Xianziyizhen recipe capsule (XRC), a kidney-tonifying herb, on the PGI2-PPARδ signaling pathway at the maternal-fetal interface in embryo implantation dysfunction (EID) mice. METHOD OF STUDY Intragastric administration of Progynova (estradiol) or XRC was performed in EID mouse model, following experimental induction of kidney deficiency by co-treatment with chemotherapy drug hydroxyurea and antiprogesterone mifepristone. The PPARδ and IL-11 mRNA expression in endometrium were detected by real-time relative reverse transcription-polymerase chain reaction (RT-PCR). Further, the protein expression of COX-2, PGI2, MMP-9, and TIMP-3 was detected in endometrial glandular epithelium and in stromal cells by immunohistochemical (IHC) assay. RESULTS The results showed that hydroxyurea and mifepristone-induced EID were associated with significantly lower PPARδ and IL-11 mRNA levels in endometrium and reduced COX-2, PGI2, MMP-9, and TIMP-3 levels in endometrial glandular epithelium, compared with normal controls. However, XRC and Progynova treatment reversed these effects, leading to significant increases in PPARδ and IL-11 mRNA expression, and COX-2, PGI2, MMP-9 and TIMP-3 protein levels, when compared with the levels observed in EID mice. CONCLUSION These results strongly suggested that XRC is beneficial in EID treatment and that XRC may mediate its effects through regulation of the PGI2-PPARδ signaling pathway.
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Affiliation(s)
- Min Xu
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Ying-Zhou Tian
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Xiu-Jun Zhu
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Xi Zhang
- Department of Gynecology, Guangzhou University of TCM, Guangzhou, China
| | - Jing-Yan Zhu
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Chun-Xiao Gu
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Yi Chen
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
| | - Jian-Ling Huang
- Department of Gynecology, Guangdong Provincial Hospital of TCM, Guangzhou, China
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Schulte MMB, Tsai JH, Moley KH. Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reprod Sci 2014; 22:6-14. [PMID: 25488942 DOI: 10.1177/1933719114561552] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Successful embryonic implantation is the result of a receptive endometrium, a functional embryo at the blastocyst stage and a synchronized dialog between maternal and embryonic tissues. Successful implantation requires the endometrium to undergo steroid-dependent change during each menstrual cycle, exhibiting a short period of embryonic receptivity known as the window of implantation. The term "endometrial receptivity" was introduced to define the state of the endometrium during the window of implantation. It refers to the ability of the endometrium to undergo changes that will allow the blastocyst to attach, penetrate, and induce localized changes in the endometrial stroma. These changes are metabolically demanding, and glucose metabolism has been proven to be important for the preparation of the endometrium for embryo implantation. Obesity and polycystic ovary syndrome (PCOS) represent 2 common metabolic disorders that are associated with subfertility. The aim of this review is to summarize the effect of obesity and PCOS on endometrial receptivity at the time of implantation. Focus will be on metabolic alterations that regulate decidualization, including glucose metabolism, hyperinsulinemia, and hyperandrogenism.
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Affiliation(s)
- Maureen M B Schulte
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jui-he Tsai
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA
| | - Kelle H Moley
- Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA
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Chang EM, Song HS, Lee DR, Lee WS, Yoon TK. In vitro maturation of human oocytes: Its role in infertility treatment and new possibilities. Clin Exp Reprod Med 2014; 41:41-6. [PMID: 25045627 PMCID: PMC4102689 DOI: 10.5653/cerm.2014.41.2.41] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 03/22/2014] [Accepted: 03/24/2014] [Indexed: 01/25/2023] Open
Abstract
IVM refers to the maturation of immature oocytes in culture after their recovery from small antral follicles at the stage prior to selection and dominance. IVM requires little or no FSH in vivo and has been proposed as an alternative to conventional IVF, since it reduces the primary adverse effects caused by controlled ovarian stimulation, including the ovarian hyperstimulation syndrome. Moreover, IVM is a promising option for cases for which no standard protocol is suitable, such as FSH resistance, contraindications for ovarian stimulatory drugs, and the need for urgent fertility preservation. Recently, IVM has been used in women with regular cycles and normal ovaries. However, the pregnancy rate following IVM is suboptimal compared with that of conventional IVF, indicating that further studies to optimize the protocol and the culture conditions are warranted.
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Affiliation(s)
- Eun Mi Chang
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Hang Seok Song
- Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Dong Ryul Lee
- Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
| | - Woo Sik Lee
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Tae Ki Yoon
- Department of Obstetrics and Gynecology, Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul, Korea
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Kim E, Seok HH, Lee SY, Lee DR, Moon J, Yoon TK, Lee WS, Lee KA. Correlation between Expression of Glucose Transporters in Granulosa Cells and Oocyte Quality in Women with Polycystic Ovary Syndrome. Endocrinol Metab (Seoul) 2014; 29:40-7. [PMID: 24741453 PMCID: PMC3970285 DOI: 10.3803/enm.2014.29.1.40] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Accepted: 10/11/2013] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The glucose transporters (GLUTs) exhibit different tissue-specific expression. This study aimed to investigate the types of GLUTs expressed in human granulosa cells (GCs) obtained from women with polycystic ovary syndrome (PCOS) and their relationship with insulin resistance (IR) and the outcomes of in vitro maturation (IVM) of immature oocytes. METHODS Expression of GLUTs was evaluated in GCs from women with PCOS with or without IR. Thirty-six women with PCOS undergoing an IVM program were included. Differential gene expression between the insulin sensitive (IS) and IR group was measured by reverse transcription polymerase chain reaction. RESULTS Expression of GLUTs 1, 3, 5, 8, and 13 was constitutive, whereas expression of GLUTs 2 and 7 was not observed in human GCs. The remaining GLUTs, 4, 6, 9, 10, 11, and 12, were differentially expressed among patients according to metabolic status, such as insulin sensitivity. A higher number of GCs from patients with IR (92%) expressed GLUT6 than GCs from IS PCOS patients (46.3%). Logistic regression showed that expression of GLUTs 9, 11, and 12 correlates with rates of IVM at 48 hours, fertilization, and implantation, respectively. CONCLUSION This is the first report describing the expression pattern of all 13 members of the GLUT family in human GCs. Results of the present study suggest that patients' insulin sensitivity regulates GLUT expression in GCs in PCOS patients, and this may control oocyte quality for IVM and subsequent processes such as fertilization and implantation in patients taking part in an in vitro fertilization program.
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Affiliation(s)
- Eunju Kim
- Department of Biomedical Science, CHA University, Seoul, Korea
| | - Hyun Ha Seok
- Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Su-Yeon Lee
- Department of Biomedical Science, CHA University, Seoul, Korea
| | - Dong Ryul Lee
- Department of Biomedical Science, CHA University, Seoul, Korea
- Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Jisook Moon
- Department of Applied Bioscience, CHA University, Seoul, Korea
| | - Tae Ki Yoon
- Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Woo Sik Lee
- Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Kyung-Ah Lee
- Department of Biomedical Science, CHA University, Seoul, Korea
- Fertility Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
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