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}
F Parisi, C Fenizia, A Introini, A Zavatta, C Scaccabarozzi, M Biasin, V Savasi
<p><strong>Background: </strong>Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.</p><p><strong>Objective and rationale: </strong>This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.</p><p><strong>Search methods: </strong>Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.</p><p><strong>Outcomes: </strong>During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.</p><p><strong>Wider implications: </strong>Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens
{"title":"The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.","authors":"F Parisi, C Fenizia, A Introini, A Zavatta, C Scaccabarozzi, M Biasin, V Savasi","doi":"10.1093/humupd/dmad016","DOIUrl":"10.1093/humupd/dmad016","url":null,"abstract":"<p><strong>Background: </strong>Estrogens regulate disparate female physiological processes, thus ensuring reproduction. Altered estrogen levels and signaling have been associated with increased risks of pregnancy failure and complications, including hypertensive disorders and low birthweight babies. However, the role of estrogens in the periconceptional period and early pregnancy is still understudied.</p><p><strong>Objective and rationale: </strong>This review aims to summarize the current evidence on the role of maternal estrogens during the periconceptional period and the first trimester of pregnancies conceived naturally and following ART. Detailed molecular mechanisms and related clinical impacts are extensively described.</p><p><strong>Search methods: </strong>Data for this narrative review were independently identified by seven researchers on Pubmed and Embase databases. The following keywords were selected: 'estrogens' OR 'estrogen level(s)' OR 'serum estradiol' OR 'estradiol/estrogen concentration', AND 'early pregnancy' OR 'first trimester of pregnancy' OR 'preconceptional period' OR 'ART' OR 'In Vitro Fertilization (IVF)' OR 'Embryo Transfer' OR 'Frozen Embryo Transfer' OR 'oocyte donation' OR 'egg donation' OR 'miscarriage' OR 'pregnancy outcome' OR 'endometrium'.</p><p><strong>Outcomes: </strong>During the periconceptional period (defined here as the critical time window starting 1 month before conception), estrogens play a crucial role in endometrial receptivity, through the activation of paracrine/autocrine signaling. A derailed estrogenic milieu within this period seems to be detrimental both in natural and ART-conceived pregnancies. Low estrogen levels are associated with non-conception cycles in natural pregnancies. On the other hand, excessive supraphysiologic estrogen concentrations at time of the LH peak correlate with lower live birth rates and higher risks of pregnancy complications. In early pregnancy, estrogen plays a massive role in placentation mainly by modulating angiogenic factor expression-and in the development of an immune-tolerant uterine micro-environment by remodeling the function of uterine natural killer and T-helper cells. Lower estrogen levels are thought to trigger abnormal placentation in naturally conceived pregnancies, whereas an estrogen excess seems to worsen pregnancy development and outcomes.</p><p><strong>Wider implications: </strong>Most current evidence available endorses a relation between periconceptional and first trimester estrogen levels and pregnancy outcomes, further depicting an optimal concentration range to optimize pregnancy success. However, how estrogens co-operate with other factors in order to maintain a fine balance between local tolerance towards the developing fetus and immune responses to pathogens remains elusive. Further studies are highly warranted, also aiming to identify the determinants of estrogen response and biomarkers for personalized estrogen administration regimens","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"699-720"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677177","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}
Nienke E van Hoogenhuijze, Gemma Lahoz Casarramona, Sarah Lensen, Cindy Farquhar, Mohan S Kamath, Aleyamma T Kunjummen, Nick Raine-Fenning, Sine Berntsen, Anja Pinborg, Shari Mackens, Zeynep Ozturk Inal, Ernest H Y Ng, Jennifer S M Mak, Sachin A Narvekar, Wellington P Martins, Mia Steengaard Olesen, Helen L Torrance, Ben W Mol, Marinus J C Eijkemans, Rui Wang, Frank J M Broekmans
<p><strong>Background: </strong>In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed.</p><p><strong>Objective and rationale: </strong>This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis.</p><p><strong>Search methods: </strong>A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET.</p><p><strong>Outcomes: </strong>Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo
{"title":"Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.","authors":"Nienke E van Hoogenhuijze, Gemma Lahoz Casarramona, Sarah Lensen, Cindy Farquhar, Mohan S Kamath, Aleyamma T Kunjummen, Nick Raine-Fenning, Sine Berntsen, Anja Pinborg, Shari Mackens, Zeynep Ozturk Inal, Ernest H Y Ng, Jennifer S M Mak, Sachin A Narvekar, Wellington P Martins, Mia Steengaard Olesen, Helen L Torrance, Ben W Mol, Marinus J C Eijkemans, Rui Wang, Frank J M Broekmans","doi":"10.1093/humupd/dmad014","DOIUrl":"10.1093/humupd/dmad014","url":null,"abstract":"<p><strong>Background: </strong>In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed.</p><p><strong>Objective and rationale: </strong>This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis.</p><p><strong>Search methods: </strong>A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET.</p><p><strong>Outcomes: </strong>Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"721-740"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667357","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}
Simon Alesi, Nahal Habibi, Thais Rasia Silva, Nicole Cheung, Sophia Torkel, Chau Thien Tay, Alejandra Quinteros, Hugo Winter, Helena Teede, Aya Mousa, Jessica A Grieger, Lisa J Moran
Background: Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility.
Objective and rationale: A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy.
Search methods: In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach.
Outcomes: A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies.
Wider implications: Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.
{"title":"Assessing the influence of preconception diet on female fertility: a systematic scoping review of observational studies.","authors":"Simon Alesi, Nahal Habibi, Thais Rasia Silva, Nicole Cheung, Sophia Torkel, Chau Thien Tay, Alejandra Quinteros, Hugo Winter, Helena Teede, Aya Mousa, Jessica A Grieger, Lisa J Moran","doi":"10.1093/humupd/dmad018","DOIUrl":"10.1093/humupd/dmad018","url":null,"abstract":"<p><strong>Background: </strong>Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility.</p><p><strong>Objective and rationale: </strong>A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy.</p><p><strong>Search methods: </strong>In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach.</p><p><strong>Outcomes: </strong>A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies.</p><p><strong>Wider implications: </strong>Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.</p>","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"811-828"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834686","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>Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.</p><p><strong>Objective and rationale: </strong>We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.</p><p><strong>Search methods: </strong>The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.</p><p><strong>Outcomes: </strong>First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique
{"title":"Dissecting mammalian reproduction with spatial transcriptomics.","authors":"Xin Zhang, Qiqi Cao, Shreya Rajachandran, Edward J Grow, Melanie Evans, Haiqi Chen","doi":"10.1093/humupd/dmad017","DOIUrl":"10.1093/humupd/dmad017","url":null,"abstract":"<p><strong>Background: </strong>Mammalian reproduction requires the fusion of two specialized cells: an oocyte and a sperm. In addition to producing gametes, the reproductive system also provides the environment for the appropriate development of the embryo. Deciphering the reproductive system requires understanding the functions of each cell type and cell-cell interactions. Recent single-cell omics technologies have provided insights into the gene regulatory network in discrete cellular populations of both the male and female reproductive systems. However, these approaches cannot examine how the cellular states of the gametes or embryos are regulated through their interactions with neighboring somatic cells in the native tissue environment owing to tissue disassociations. Emerging spatial omics technologies address this challenge by preserving the spatial context of the cells to be profiled. These technologies hold the potential to revolutionize our understanding of mammalian reproduction.</p><p><strong>Objective and rationale: </strong>We aim to review the state-of-the-art spatial transcriptomics (ST) technologies with a focus on highlighting the novel biological insights that they have helped to reveal about the mammalian reproductive systems in the context of gametogenesis, embryogenesis, and reproductive pathologies. We also aim to discuss the current challenges of applying ST technologies in reproductive research and provide a sneak peek at what the field of spatial omics can offer for the reproduction community in the years to come.</p><p><strong>Search methods: </strong>The PubMed database was used in the search for peer-reviewed research articles and reviews using combinations of the following terms: 'spatial omics', 'fertility', 'reproduction', 'gametogenesis', 'embryogenesis', 'reproductive cancer', 'spatial transcriptomics', 'spermatogenesis', 'ovary', 'uterus', 'cervix', 'testis', and other keywords related to the subject area. All relevant publications until April 2023 were critically evaluated and discussed.</p><p><strong>Outcomes: </strong>First, an overview of the ST technologies that have been applied to studying the reproductive systems was provided. The basic design principles and the advantages and limitations of these technologies were discussed and tabulated to serve as a guide for researchers to choose the best-suited technologies for their own research. Second, novel biological insights into mammalian reproduction, especially human reproduction revealed by ST analyses, were comprehensively reviewed. Three major themes were discussed. The first theme focuses on genes with non-random spatial expression patterns with specialized functions in multiple reproductive systems; The second theme centers around functionally interacting cell types which are often found to be spatially clustered in the reproductive tissues; and the thrid theme discusses pathological states in reproductive systems which are often associated with unique","PeriodicalId":55045,"journal":{"name":"Human Reproduction Update","volume":" ","pages":"794-810"},"PeriodicalIF":14.8,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677176","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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