Amerigo Vitagliano, Ettore Cicinelli, Antonio Simone Laganà, Alessandro Favilli, Salvatore Giovanni Vitale, Marco Noventa, Gianluca Raffaello Damiani, Miriam Dellino, Pierpaolo Nicolì, Antonio D'Amato, Stefano Bettocchi, Maria Matteo, Stefano Palomba
{"title":"Endometrial scratching: the light at the end of the tunnel.","authors":"Amerigo Vitagliano, Ettore Cicinelli, Antonio Simone Laganà, Alessandro Favilli, Salvatore Giovanni Vitale, Marco Noventa, Gianluca Raffaello Damiani, Miriam Dellino, Pierpaolo Nicolì, Antonio D'Amato, Stefano Bettocchi, Maria Matteo, Stefano Palomba","doi":"10.1093/humupd/dmad037","DOIUrl":"10.1093/humupd/dmad037","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"238-239"},"PeriodicalIF":14.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The complicated ART of finding consensus on family-building health policy: a comment on the IFFS consensus document.","authors":"Alexander Weinreb, Artur Ludwin, Hagai Levine","doi":"10.1093/humupd/dmad036","DOIUrl":"10.1093/humupd/dmad036","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"131-132"},"PeriodicalIF":14.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgina L Jones, Kirsty Budds, Francesca Taylor, Danielle Musson, Justin Raymer, David Churchman, Stephen H Kennedy, Crispin Jenkinson
<p><strong>Background: </strong>The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified.</p><p><strong>Objective and rationale: </strong>The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL. Applying robust systematic review methodology, following PRISMA guidelines, we sought to answer: How many studies have used the EHP and for what purpose?; What are the demographic characteristics and international context of the studies?; What is the methodological nature and quality of the studies?; Which interventions have been assessed and what are the reported EHP outcomes?; and Can the EHP outcomes of these interventions be analysed using a meta-analysis and, if so, what do the results show?</p><p><strong>Search methods: </strong>The electronic databases MEDLINE, CINAHL, PsycINFO, PubMed, and Google Scholar were searched from the year the EHP was first published, in 2001 to 26 February 2020 using the search terms 'EHP30', 'EHP5', 'EHP-30', 'EHP-5', 'endometriosis health profile 30', and 'endometriosis health profile 5'. We updated the searches on 9 April 2021. All included studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT).</p><p><strong>Outcomes: </strong>The review included 139 papers. In clinical intervention studies, the EHPs were deployed most frequently to measure the outcomes of medical (n = 35) and surgical (n = 21) treatment. The EHPs were also used in 13 other intervention studies, 29 non-interventional studies, 32 psychometric/cross cultural validation studies; six diagnostic studies, and in three other studies to measure outcomes in related conditions. They were mainly deployed in studies undertaken in Europe and North America. Overall, regardless of the nature of the intervention, most women reported improvements in HRQoL after treatment. Surgical interventions generally resulted in significant improvements for the longest amount of time. There was also evidence that when participants stopped taking medication their EHP scores worsened, perhaps reinforcing the temporary impact of medical treatment. Younger patients reported more negative impact upon their HRQoL. Further evidence using classical test theory to support the EHPs' robust psychometric properties, including acceptability, dimensionality, reliability, validity (including cross-cultural), and responsiveness, was demonstrated, particularly for the EHP-30. Strikingly, using anchor-based methods, EHP-30 responsiveness studies demon
{"title":"A systematic review to determine use of the Endometriosis Health Profiles to measure quality of life outcomes in women with endometriosis.","authors":"Georgina L Jones, Kirsty Budds, Francesca Taylor, Danielle Musson, Justin Raymer, David Churchman, Stephen H Kennedy, Crispin Jenkinson","doi":"10.1093/humupd/dmad029","DOIUrl":"10.1093/humupd/dmad029","url":null,"abstract":"<p><strong>Background: </strong>The Endometriosis Health Profiles (EHPs), the EHP-30 and EHP-5, are patient-reported outcome measures that were developed to measure the health-related quality of life (HRQoL) of women living with endometriosis. Prior to their development, a systematic review was undertaken which identified that the HRQoL of women living with endometriosis was poorly understood, with only three medical and one surgical study identified.</p><p><strong>Objective and rationale: </strong>The 20-year anniversary of the EHP-30 provided a timely opportunity to assess how the tools have been used and explore what the findings tell us about the impact of endometriosis and its associated treatments upon women's QoL. Applying robust systematic review methodology, following PRISMA guidelines, we sought to answer: How many studies have used the EHP and for what purpose?; What are the demographic characteristics and international context of the studies?; What is the methodological nature and quality of the studies?; Which interventions have been assessed and what are the reported EHP outcomes?; and Can the EHP outcomes of these interventions be analysed using a meta-analysis and, if so, what do the results show?</p><p><strong>Search methods: </strong>The electronic databases MEDLINE, CINAHL, PsycINFO, PubMed, and Google Scholar were searched from the year the EHP was first published, in 2001 to 26 February 2020 using the search terms 'EHP30', 'EHP5', 'EHP-30', 'EHP-5', 'endometriosis health profile 30', and 'endometriosis health profile 5'. We updated the searches on 9 April 2021. All included studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT).</p><p><strong>Outcomes: </strong>The review included 139 papers. In clinical intervention studies, the EHPs were deployed most frequently to measure the outcomes of medical (n = 35) and surgical (n = 21) treatment. The EHPs were also used in 13 other intervention studies, 29 non-interventional studies, 32 psychometric/cross cultural validation studies; six diagnostic studies, and in three other studies to measure outcomes in related conditions. They were mainly deployed in studies undertaken in Europe and North America. Overall, regardless of the nature of the intervention, most women reported improvements in HRQoL after treatment. Surgical interventions generally resulted in significant improvements for the longest amount of time. There was also evidence that when participants stopped taking medication their EHP scores worsened, perhaps reinforcing the temporary impact of medical treatment. Younger patients reported more negative impact upon their HRQoL. Further evidence using classical test theory to support the EHPs' robust psychometric properties, including acceptability, dimensionality, reliability, validity (including cross-cultural), and responsiveness, was demonstrated, particularly for the EHP-30. Strikingly, using anchor-based methods, EHP-30 responsiveness studies demon","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"186-214"},"PeriodicalIF":14.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments.</p><p><strong>Objective and rationale: </strong>The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment.</p><p><strong>Search methods: </strong>PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed.</p><p><strong>Outcomes: </strong>A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment.</p><p><strong>Wider implications: </strong>The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), acti
{"title":"Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review.","authors":"Yiqiu Wei, Jingxuan Wang, Rui Qu, Weiqian Zhang, Yiling Tan, Yanwei Sha, Lin Li, Tailang Yin","doi":"10.1093/humupd/dmad026","DOIUrl":"10.1093/humupd/dmad026","url":null,"abstract":"<p><strong>Background: </strong>Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments.</p><p><strong>Objective and rationale: </strong>The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment.</p><p><strong>Search methods: </strong>PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed.</p><p><strong>Outcomes: </strong>A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment.</p><p><strong>Wider implications: </strong>The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), acti","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"48-80"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41141146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangming Zhong, Jianlin Li, Graham J Burton, Hannu Koistinen, Ka Wang Cheung, Ernest H Y Ng, Yuanqing Yao, William S B Yeung, Cheuk-Lun Lee, Philip C N Chiu
<p><strong>Background: </strong>The establishment of maternal-fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal-fetal interface and their associations with pathological processes.</p><p><strong>Objective and rationale: </strong>This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal-fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal-fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal-fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included.</p><p><strong>Outcomes: </strong>The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal-fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal-fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal-fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groun
{"title":"The functional roles of protein glycosylation in human maternal-fetal crosstalk.","authors":"Jiangming Zhong, Jianlin Li, Graham J Burton, Hannu Koistinen, Ka Wang Cheung, Ernest H Y Ng, Yuanqing Yao, William S B Yeung, Cheuk-Lun Lee, Philip C N Chiu","doi":"10.1093/humupd/dmad024","DOIUrl":"10.1093/humupd/dmad024","url":null,"abstract":"<p><strong>Background: </strong>The establishment of maternal-fetal crosstalk is vital to a successful pregnancy. Glycosylation is a post-translational modification in which glycans (monosaccharide chains) are attached to an organic molecule. Glycans are involved in many physiological and pathological processes. Human endometrial epithelium, endometrial gland secretions, decidual immune cells, and trophoblasts are highly enriched with glycoconjugates and glycan-binding molecules important for a healthy pregnancy. Aberrant glycosylation in the placenta and uterus has been linked to repeated implantation failure and various pregnancy complications, but there is no recent review summarizing the functional roles of glycosylation at the maternal-fetal interface and their associations with pathological processes.</p><p><strong>Objective and rationale: </strong>This review aims to summarize recent findings on glycosylation, glycosyltransferases, and glycan-binding receptors at the maternal-fetal interface, and their involvement in regulating the biology and pathological conditions associated with endometrial receptivity, placentation and maternal-fetal immunotolerance. Current knowledge limitations and future insights into the study of glycobiology in reproduction are discussed.</p><p><strong>Search methods: </strong>A comprehensive PubMed search was conducted using the following keywords: glycosylation, glycosyltransferases, glycan-binding proteins, endometrium, trophoblasts, maternal-fetal immunotolerance, siglec, selectin, galectin, repeated implantation failure, early pregnancy loss, recurrent pregnancy loss, preeclampsia, and fetal growth restriction. Relevant reports published between 1980 and 2023 and studies related to these reports were retrieved and reviewed. Only publications written in English were included.</p><p><strong>Outcomes: </strong>The application of ultrasensitive mass spectrometry tools and lectin-based glycan profiling has enabled characterization of glycans present at the maternal-fetal interface and in maternal serum. The endometrial luminal epithelium is covered with highly glycosylated mucin that regulates blastocyst adhesion during implantation. In the placenta, fucose and sialic acid residues are abundantly presented on the villous membrane and are essential for proper placentation and establishment of maternal-fetal immunotolerance. Glycan-binding receptors, including selectins, sialic-acid-binding immunoglobulin-like lectins (siglecs) and galectins, also modulate implantation, trophoblast functions and maternal-fetal immunotolerance. Aberrant glycosylation is associated with repeated implantation failure, early pregnancy loss and various pregnancy complications. The current limitation in the field is that most glycobiological research relies on association studies, with few studies revealing the specific functions of glycans. Technological advancements in analytic, synthetic and functional glycobiology have laid the groun","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"81-108"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10572145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Finding a way through the review maze: systematic, scoping, or an overview.","authors":"Madelon van Wely","doi":"10.1093/humupd/dmad032","DOIUrl":"10.1093/humupd/dmad032","url":null,"abstract":"","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":"30 1","pages":"1-2"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robert B Gilchrist, Tuong M Ho, Michel De Vos, Flor Sanchez, Sergio Romero, William L Ledger, Ellen Anckaert, Lan N Vuong, Johan Smitz
<p><strong>Background: </strong>While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.</p><p><strong>Objective and rationale: </strong>The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed.</p><p><strong>Search methods: </strong>Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS.</p><p><strong>Outcomes: </strong>Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.</p><p><strong>Wider implications: </strong>Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in anim
背景：虽然卵母细胞体外受精在全球范围内都有零星的临床实践，但并没有得到广泛应用。不过，最近我们对动物研究中卵母细胞生物学和排卵基本方面的理解取得了一些开创性的进展，从而产生了新的 IVM 方法。双相体外受精法是体外受精技术最近取得的一项重大进展。这包括从受到微量刺激的患者/动物的小前卵泡中收集未成熟卵母细胞（无需 hCG-刺激），并在 IVM 之前在先进的培养系统中对卵母细胞进行 24 小时的预培养（"pre-IVM"），然后进行常规 IVF 程序。如果安全有效，这种新型程序可能会对人类 ART 实践产生重大影响。目的和依据：本综述旨在研究卵巢生物学的主要科学进展，特别关注 IVM 前方法的发展，深入探讨双相 IVM 程序，并报告动物和临床人类数据的结果，包括安全性数据。文章还讨论了双相静脉输液对 ART 实践的潜在影响：本综述从 PubMed 和 Web of Science 搜索结果中选取了同行评议的原创文章和综述文章。搜索时使用了以下关键词：卵母细胞体外受精、体外受精前、双相体外受精、CAPA-IVM、hCG-触发/刺激体外受精、自然周期体外受精/M、体外受精、OTO-IVM、卵母细胞成熟、减数分裂能力、卵母细胞发育能力、卵母细胞获能、卵泡大小、积壳细胞（CC）、颗粒细胞、COC、间隙连接通讯、跨区过程、cAMP 与体外受精、cGMP 与体外受精、CNP 与体外受精、类 EGF 肽与体外受精、最小刺激 ART、多囊卵巢综合征。结果：尽量减少促性腺激素的使用意味着 IVM 卵母细胞将从含有仍在发育的卵母细胞的小前区（前优势）卵泡中采集。使用此类卵母细胞进行标准体外受精会产生不理想的临床结果，而体外受精前卵母细胞移植的目的是在体外受精前继续卵母细胞的体外发育。预体外受精是通过引起卵母细胞CC发生深刻的细胞变化来实现的，CC在预体外受精阶段继续满足卵母细胞的发育需求。文献中包含了 25 年来对各种前体外受精和双相体外受精程序的动物研究，为人类体外受精的新方法提供了大量的知识基础。一种基于 c 型钠尿肽的体外受精前程序（名为 "获能-体外受精"（CAPA-IVM））已通过了临床前人体安全性和有效性试验，将其应用于临床实践后，健康活产率与传统体外受精并无不同：几十年来，临床体外受精的改进一直是循序渐进的，但随着动物卵母细胞生物学的里程碑式发现最终应用于临床实践，过去几年可能出现了转机，从而改善了患者的治疗效果。CAPA-IVM 是首个经过临床试验的双相体外受精系统，其良好的临床结果表明，体外受精作为一种替代性、低干预、低成本、安全、患者友好的抗逆转录病毒疗法，尤其是对多囊卵巢综合症患者来说，再次引起了人们的兴趣。同样的新方法也被用于癌症患者的生育力保存，并有望用于社会卵母细胞冷冻。
{"title":"A fresh start for IVM: capacitating the oocyte for development using pre-IVM.","authors":"Robert B Gilchrist, Tuong M Ho, Michel De Vos, Flor Sanchez, Sergio Romero, William L Ledger, Ellen Anckaert, Lan N Vuong, Johan Smitz","doi":"10.1093/humupd/dmad023","DOIUrl":"10.1093/humupd/dmad023","url":null,"abstract":"<p><strong>Background: </strong>While oocyte IVM is practiced sporadically it has not achieved widespread clinical practice globally. However, recently there have been some seminal advances in our understanding of basic aspects of oocyte biology and ovulation from animal studies that have led to novel approaches to IVM. A significant recent advance in IVM technology is the use of biphasic IVM approaches. These involve the collection of immature oocytes from small antral follicles from minimally stimulated patients/animals (without hCG-priming) and an ∼24 h pre-culture of oocytes in an advanced culture system ('pre-IVM') prior to IVM, followed by routine IVF procedures. If safe and efficacious, this novel procedure may stand to make a significant impact on human ART practices.</p><p><strong>Objective and rationale: </strong>The objectives of this review are to examine the major scientific advances in ovarian biology with a unique focus on the development of pre-IVM methodologies, to provide an insight into biphasic IVM procedures, and to report on outcomes from animal and clinical human data, including safety data. The potential future impact of biphasic IVM on ART practice is discussed.</p><p><strong>Search methods: </strong>Peer review original and review articles were selected from PubMed and Web of Science searches for this narrative review. Searches were performed using the following keywords: oocyte IVM, pre-IVM, biphasic IVM, CAPA-IVM, hCG-triggered/primed IVM, natural cycle IVF/M, ex-vivo IVM, OTO-IVM, oocyte maturation, meiotic competence, oocyte developmental competence, oocyte capacitation, follicle size, cumulus cell (CC), granulosa cell, COC, gap-junction communication, trans-zonal process, cAMP and IVM, cGMP and IVM, CNP and IVM, EGF-like peptide and IVM, minimal stimulation ART, PCOS.</p><p><strong>Outcomes: </strong>Minimizing gonadotrophin use means IVM oocytes will be collected from small antral (pre-dominant) follicles containing oocytes that are still developing. Standard IVM yields suboptimal clinical outcomes using such oocytes, whereas pre-IVM aims to continue the oocyte's development ex vivo, prior to IVM. Pre-IVM achieves this by eliciting profound cellular changes in the oocyte's CCs, which continue to meet the oocyte's developmental needs during the pre-IVM phase. The literature contains 25 years of animal research on various pre-IVM and biphasic IVM procedures, which serves as a large knowledge base for new approaches to human IVM. A pre-IVM procedure based on c-type natriuretic peptide (named 'capacitation-IVM' (CAPA-IVM)) has undergone pre-clinical human safety and efficacy trials and its adoption into clinical practice resulted in healthy live birth rates not different from conventional IVF.</p><p><strong>Wider implications: </strong>Over many decades, improvements in clinical IVM have been gradual and incremental but there has likely been a turning of the tide in the past few years, with landmark discoveries in anim","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"3-25"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Background: </strong>Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt.</p><p><strong>Objective and rationale: </strong>The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART.</p><p><strong>Search methods: </strong>An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues.</p><p><strong>Outcomes: </strong>ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications.</p><p><strong>Wider implications: </strong>Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it
背景：全世界已有数百万儿童在人工生殖技术的帮助下出生，但人工生殖技术的无害性尚未得到充分证明。多年来，评估抗逆转录病毒疗法具体效果的工作主要集中在胚胎上；然而，决定未来胚胎发育潜力的首先是卵母细胞的质量。卵巢刺激、冷冻保存和 IVM 有时是获得成熟卵母细胞的必要步骤，但它们可能会改变卵母细胞基因组的适当表达。此外，女性不孕症、环境因素和生活方式也可能对卵母细胞转录组的质量产生重大影响，从而干扰 ART 尝试的结果。目的和依据：本综述旨在确定人类卵母细胞转录组的变化是由 ART 的特定干预措施以及年龄、生殖健康问题和生活方式等内在因素引起的。我们还为今后尝试 ART 时应采取的良好做法提供了建议：在PubMed上进行了深入的文献检索，以确定评估ART干预后人类卵母细胞转录组的研究，或在母体衰老、次优生活方式或生殖健康问题的背景下进行的研究：抗逆转录病毒疗法的成功易受外部因素、孕产妇衰老、生活方式因素（吸烟、体重指数）以及子宫内膜异位症或多囊卵巢综合征导致的不孕症的影响。事实上，所有这些都有可能增加氧化应激，改变线粒体的前处理过程。关于 ART 技术本身，有证据表明不同的卵巢刺激方案会影响卵母细胞转录组。线粒体、氧化磷酸化和新陈代谢的相关过程会受到 IVM 的干扰。低温保存可能会使转录调控、泛素化、细胞周期和卵母细胞生长途径的基因失调。至于其他 ART 实验室因素，如温度、氧张力、空气污染和光照，相关证据仍然很少。我们重点研究了参与染色质过程的基因，如 DNA 甲基化、异染色质调节、组蛋白修饰和染色质重塑复合物，以及基因组印记，观察到这些基因在 ART 干预或生活方式暴露后，以及由于母体衰老和生殖疾病等内部因素引起的系统性失调。这些表观遗传调节因子表达的改变可能是与不利的卵母细胞环境相关的共同机制，从而解释了全球转录组的改变：更广泛的影响：许多试管婴儿因素和其他外部因素都有可能损害卵母细胞转录组的完整性，这对发育中的胚胎可能并非无害。幸运的是，通过调整 ART 方案或减少不良暴露，很可能会将此类失调降至最低。
{"title":"Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects.","authors":"Bastien Ducreux, Catherine Patrat, Jacquetta Trasler, Patricia Fauque","doi":"10.1093/humupd/dmad025","DOIUrl":"10.1093/humupd/dmad025","url":null,"abstract":"<p><strong>Background: </strong>Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt.</p><p><strong>Objective and rationale: </strong>The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART.</p><p><strong>Search methods: </strong>An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues.</p><p><strong>Outcomes: </strong>ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications.</p><p><strong>Wider implications: </strong>Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"26-47"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeffrey Pea, Jahnay Bryan, Cynthia Wan, Alexis L Oldfield, Kiran Ganga, Faith E Carter, Lynn M Johnson, Marla E Lujan
<p><strong>Background: </strong>Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS.</p><p><strong>Search methods: </strong>Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves.</p><p><strong>Outcomes: </strong>From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggest
背景：多囊卵巢形态（PCOM）超声检查被认为是多囊卵巢综合征（PCOS）的主要特征。最新的《国际多囊卵巢综合征评估和管理循证指南》重申了其作为多囊卵巢综合症诊断标准的相关性。然而目前尚不清楚定义多囊卵巢综合征的最佳实践和特定超声标记物。目的和原理：本系统综述和诊断荟萃分析的目的是评估卵巢形态的各种超声特征在多囊卵巢综合症诊断中的准确性。检索方法：1990年1月1日至6月12日发表的相关研究2023个是通过PubMed、Web of Science、Scopus、CINAHL和CENTRAL的系统搜索确定的。使用以下超声标记物生成多囊卵巢综合征诊断准确性指标（如拟议阈值、敏感性、特异性）的研究符合纳入标准：每个卵巢的卵泡数（FNPO）或单个横截面的卵泡数、卵巢体积（OV）和基质特征。排除了对孕妇或绝经后妇女的研究。诊断测试准确性研究的偏倚风险和适用性评估分别使用单指标测试或多指标测试之间的QUADAS-2和QUADAS-C工具确定。使用敏感性和特异性合并的双变量模型进行诊断荟萃分析，并使用森林图和受试者操作特征汇总曲线（SROC）进行可视化。结果：从最初确定的2197份记录中，纳入了31项研究。由于研究人群重复或指数测试数据有限，五项和两项研究的数据被排除在荟萃分析之外，剩下24项研究。20项成人研究的汇总结果包括3883名对照参与者和3859名多囊卵巢综合征患者。FNPO是成年女性最准确的诊断标志物（敏感性：84%，CI:81-87%；特异性：91%，CI:86-94%；AUC:0.905）。OV和FNPS具有相似的合并敏感性（OV:81%，CI:76-86%；FNPS:81%，CI：70-89%），但与FNPO相比，合并特异性较差（OV:80%，CI:75-86%；FNPS-83%，CI:75-98%）和AUC（OV:0.856；FNPS:0.870）。由210名对照参与者和268名多囊卵巢综合征女孩组成的四项青少年研究的汇总结果表明，尽管目前的证据仍然有限，但OV可能是多囊卵巢综合症诊断的有力超声标记。大多数研究在所有超声标记物的患者选择（例如缺乏随机/连续的患者选择）和指标测试（例如缺乏预先提出的比较阈值）领域存在高偏倚风险。因此，诊断荟萃分析无法确定超声标记物诊断多囊卵巢综合征的最准确界限。亚组分析表明，基于先前提出的诊断阈值、年龄、BMI或技术的分层并不能解释研究中观察到的诊断准确性的异质性。使用鹿特丹标准诊断多囊卵巢综合征的研究提高了FNPO的敏感性。与亚洲研究（FNPO：敏感性）和欧洲研究（OV：特异性、诊断比值比和阳性似然比）相比，北美研究的诊断准确性较低。诊断准确性的地理差异可能是由于不同地区PCOS组的年龄、BMI和诊断标准的差异。更广泛的意义：这项诊断荟萃分析支持将FNPO作为成年女性多囊卵巢综合征超声诊断的金标准。OV和FNPS在无法准确获得窦卵泡总数的情况下提供了替代方案。随着更多的数据可用，我们的发现支持了青少年多囊卵巢综合征超声证据的潜力。亚组分析表明，有必要调查地理差异对多囊卵巢综合征表型的任何相对贡献。这些发现可能为制定PCOM的标准化定义和更准确的PCOS超声评估策略和最佳实践提供基础。
{"title":"Ultrasonographic criteria in the diagnosis of polycystic ovary syndrome: a systematic review and diagnostic meta-analysis.","authors":"Jeffrey Pea, Jahnay Bryan, Cynthia Wan, Alexis L Oldfield, Kiran Ganga, Faith E Carter, Lynn M Johnson, Marla E Lujan","doi":"10.1093/humupd/dmad027","DOIUrl":"10.1093/humupd/dmad027","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary morphology (PCOM) on ultrasonography is considered as a cardinal feature of polycystic ovarian syndrome (PCOS). Its relevance as a diagnostic criterion for PCOS was reaffirmed in the most recent International Evidence-Based Guideline for the Assessment and Management of PCOS. However, there remains a lack of clarity regarding the best practices and specific ultrasonographic markers to define PCOM.</p><p><strong>Objective and rationale: </strong>The aim of this systematic review and diagnostic meta-analysis was to assess the diagnostic accuracy of various ultrasonographic features of ovarian morphology in the diagnosis of PCOS.</p><p><strong>Search methods: </strong>Relevant studies published from 1 January 1990 to 12 June 2023 were identified by a systematic search in PubMed, Web of Science, Scopus, CINAHL, and CENTRAL. Studies that generated diagnostic accuracy measures (e.g. proposed thresholds, sensitivity, specificity) for PCOS using the following ultrasonographic markers met criteria for inclusion: follicle number per ovary (FNPO) or per single cross-section (FNPS), ovarian volume (OV), and stromal features. Studies on pregnant or post-menopausal women were excluded. Risk of bias and applicability assessment for diagnostic test accuracy studies were determined using the QUADAS-2 and QUADAS-C tool for a single index test or between multiple index tests, respectively. Diagnostic meta-analysis was conducted using a bivariate model of pooled sensitivity and specificity, and visualized using forest plots and summary receiver-operating characteristic (SROC) curves.</p><p><strong>Outcomes: </strong>From a total of 2197 records initially identified, 31 studies were included. Data from five and two studies were excluded from the meta-analysis due to duplicate study populations or limited data for the index test, leaving 24 studies. Pooled results of 20 adult studies consisted of 3883 control participants and 3859 individuals with PCOS. FNPO was the most accurate diagnostic marker (sensitivity: 84%, CI: 81-87%; specificity: 91%, CI: 86-94%; AUC: 0.905) in adult women. OV and FNPS had similar pooled sensitivities (OV: 81%, CI: 76-86%; FNPS: 81%, CI: 70-89%) but inferior pooled specificities (OV: 81%, CI: 75-86%; FNPS: 83%, CI: 75-88%) and AUCs (OV: 0.856; FNPS: 0.870) compared to FNPO. Pooled results from four adolescent studies consisting of 210 control participants and 268 girls with PCOS suggested that OV may be a robust ultrasonographic marker for PCOS diagnosis albeit the current evidence remains limited. The majority of the studies had high risk of bias for the patient selection (e.g. lack of randomized/consecutive patient selection) and index test (e.g. lack of pre-proposed thresholds for comparison) domains across all ultrasonographic markers. As such, diagnostic meta-analysis was unable to determine the most accurate cutoff for ultrasonographic markers to diagnose PCOS. Subgroup analysis suggest","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"109-130"},"PeriodicalIF":14.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amruta D S Pathare, Marina Loid, Merli Saare, Sebastian Brusell Gidlöf, Masoud Zamani Esteki, Ganesh Acharya, Maire Peters, Andres Salumets
<p><strong>Background: </strong>Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility.</p><p><strong>Objective and rationale: </strong>The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.</p><p><strong>Search methods: </strong>The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded.</p><p><strong>Outcomes: </strong>In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity.</p><p><strong>Wider implications: </strong>Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age h
{"title":"Endometrial receptivity in women of advanced age: an underrated factor in infertility.","authors":"Amruta D S Pathare, Marina Loid, Merli Saare, Sebastian Brusell Gidlöf, Masoud Zamani Esteki, Ganesh Acharya, Maire Peters, Andres Salumets","doi":"10.1093/humupd/dmad019","DOIUrl":"10.1093/humupd/dmad019","url":null,"abstract":"<p><strong>Background: </strong>Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility.</p><p><strong>Objective and rationale: </strong>The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.</p><p><strong>Search methods: </strong>The review was prepared using PubMed (Medline) until February 2023 with the keywords such as 'endometrial aging', 'receptivity', 'decidualization', 'hormone', 'senescence', 'cellular', 'molecular', 'methylation', 'biological age', 'epigenetic', 'oocyte recipient', 'oocyte donation', 'embryo transfer', and 'pregnancy rate'. Articles in a language other than English were excluded.</p><p><strong>Outcomes: </strong>In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women's age on endometrial receptivity.</p><p><strong>Wider implications: </strong>Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age h","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"773-793"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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