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Mitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction. 线粒体是生殖衰老和生殖能力的决定因素:对辅助生殖中胚胎能力诊断的影响。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae171
Raziye Melike Yildirim, Emre Seli

Mitochondria are commonly recognized as the powerhouses of the cell, primarily responsible for energy production through oxidative phosphorylation. Alongside this vital function, they also play crucial roles in regulating calcium signaling, maintaining membrane potential, and modulating apoptosis. Their involvement in various cellular pathways becomes particularly evident during oogenesis and embryogenesis, where mitochondrial quantity, morphology, and distribution are tightly controlled. The efficiency of the mitochondrial network is maintained through multiple quality control mechanisms that are essential for reproductive success. These include mitochondrial unfolded protein response, mitochondrial dynamics, and mitophagy. Not surprisingly, mitochondrial dysfunction has been implicated in infertility and ovarian aging, prompting investigation into mitochondria as diagnostic and therapeutic targets in assisted reproduction. To date, mitochondrial DNA copy number in oocytes, cumulus cells, and trophectoderm biopsies, and fluorescent lifetime imaging microscopy-based assessment of NADH and flavin adenine dinucleotide content have been explored as potential predictors of embryo competence, yielding limited success. Despite challenges in the clinical application of mitochondrial diagnostic strategies, these enigmatic organelles have a significant impact on reproduction, and their potential role as diagnostic targets in assisted reproduction is likely to remain an active area of investigation in the foreseeable future.

线粒体是公认的细胞动力室,主要负责通过氧化磷酸化产生能量。除了这一重要功能外,线粒体还在调节钙信号、维持膜电位和调节细胞凋亡方面发挥着关键作用。线粒体在各种细胞途径中的参与在卵子发生和胚胎发育过程中尤为明显,线粒体的数量、形态和分布都受到严格控制。线粒体网络的效率是通过多种质量控制机制来维持的,这些机制对繁殖成功至关重要。这些机制包括线粒体未折叠蛋白反应、线粒体动力学和有丝分裂。毫不奇怪,线粒体功能障碍与不孕症和卵巢衰老有牵连,这促使人们将线粒体作为辅助生殖的诊断和治疗靶点进行研究。迄今为止,线粒体 DNA 在卵母细胞、积壳细胞和滋养层活组织检查中的拷贝数,以及基于荧光寿命成像显微镜对 NADH 和黄素腺嘌呤二核苷酸含量的评估,已被探索作为胚胎能力的潜在预测指标,但成效有限。尽管线粒体诊断策略的临床应用面临挑战,但这些神秘的细胞器对生殖有重大影响,在可预见的未来,它们作为辅助生殖诊断目标的潜在作用可能仍是一个活跃的研究领域。
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引用次数: 0
Reply. Exploring the impact of fertility-preserving treatment on pregnancy: key issues in patients with endometrial cancer and atypical hyperplasia. 回复。探讨保留生育功能的治疗对怀孕的影响:子宫内膜癌和非典型增生患者的关键问题。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae188
Radostina Vasileva, Martin Koskas
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引用次数: 0
Empowering nurses and midwives: the evidence-base for the Nurses and Midwives Certification Programme of ESHRE†. 增强护士和助产士的能力:ESHRE† 护士和助产士认证计划的证据基础。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae175
S Somers, H Cotton, H Kendrew, J Pomper, A Pinborg, I R Jorgensen, C Plas, E H Hanenberg, V L Peddie, E A F Dancet
<p><strong>Study question: </strong>How were the logbook and curriculum for the Nurses and Midwives Certification Programme of ESHRE developed?</p><p><strong>Summary answer: </strong>The logbook and corresponding curriculum for the ESHRE Nurses and Midwives Certification Programme were based on an extensive literature review, an international expert panel, and a survey of Belgian and Dutch nurses and midwives (N&M) working in reproductive medicine (RM).</p><p><strong>What is known already: </strong>ESHRE has been running a certification programme for N&M working in RM since 2015. To the best of our knowledge, clinical practice guidelines for nursing/midwifery care within RM are lacking as is consensus on role descriptors of N&M working in RM.</p><p><strong>Study design, size, duration: </strong>The Nurses and Midwives Certification Committee (NMCC), established by the ESHRE Executive Committee in 2012, decided to gather background information by: (i) systematically reviewing the literature on the tasks of N&M working in RM, (ii) consulting and surveying an expert panel of international senior N&M, and (iii) surveying Belgian and Dutch N&M working in RM across different clinics. Finally, the NMCC developed a logbook and curriculum fostering a more expanded theoretic background.</p><p><strong>Participants/materials, setting, methods: </strong>The NMCC comprised four N&M, one clinical embryologist, and one gynaecologist (both in an advisory capacity). The Medline database was searched for papers relating to the tasks of N&M working in RM, by entering a search string in PubMed. In an attempt to capture insight into the tasks and roles of N&M working in RM, the NMCC subsequently surveyed N&M experts across nine countries (Denmark, Finland, France, Norway, Slovenia, Sweden, Turkey, Ukraine, and the UK), and 48 Belgian and Dutch N&M working in RM.</p><p><strong>Main results and the role of chance: </strong>There were 36 papers on the tasks of N&M working in RM originating from 13 countries (in Asia, Oceania, Europe, and North America), identified. Initially, 43 tasks in which N&M working in RM participated, were identified by literature only (n = 5), the international expert panel only (n = 4), Belgian and Dutch N&M working in RM only (n = 5), or a combination of two (n = 13) or three (n = 16) of these sources. The number and composition of tasks included in the logbook were adapted yearly based on novel insights by the NMCC. In response to the annual review, the extended role of N&M working in RM is now reflected in the 2024 version by 73 tasks. Seven specialist tasks (i.e. embryo transfer) were performed independently by N&M working in RM in some countries, while in other countries N&M merely had an 'assisting' role. Candidates are also expected to submit a mature ethical reflection on one clinical case. To support applicants throughout the certification process, the NMCC developed a curriculum in line with all tasks of N&M working in RM.</p><p><stron
研究问题:ESHRE 护士和助产士认证计划的日志和课程是如何制定的?ESHRE 护士和助产士认证计划的日志和相应课程基于广泛的文献综述、国际专家小组以及对比利时和荷兰从事生殖医学(RM)工作的护士和助产士(N&M)的调查:ESHRE 自 2015 年以来一直在为从事生殖医学工作的 N&M 开展认证计划。据我们所知,目前尚缺乏生殖医学护理/助产护理的临床实践指南,也未就生殖医学护理/助产护理的角色描述达成共识:护士和助产士认证委员会(NMCC)由 ESHRE 执行委员会于 2012 年成立,决定通过以下方式收集背景信息:(i)系统地查阅有关在生殖医学领域工作的护士和助产士任务的文献,(ii)咨询和调查国际资深护士和助产士专家小组,(iii)调查在不同诊所从事生殖医学工作的比利时和荷兰护士和助产士。最后,NMCC 编制了日志和课程,以促进更广泛的理论背景:NMCC 由四名 N&M、一名临床胚胎学家和一名妇科医生(均为顾问)组成。通过在 PubMed 中输入搜索字符串,在 Medline 数据库中搜索与在 RM 中工作的 N&M 任务相关的论文。为了深入了解在生殖健康领域工作的 N&M 的任务和角色,NMCC 随后对 9 个国家(丹麦、芬兰、法国、挪威、斯洛文尼亚、瑞典、土耳其、乌克兰和英国)的 N&M 专家以及 48 名在生殖健康领域工作的比利时和荷兰 N&M 进行了调查:共有来自 13 个国家(亚洲、大洋洲、欧洲和北美洲)的 36 篇关于从事 RM 工作的 N&M 任务的论文。最初,仅通过文献(n = 5)、仅通过国际专家小组(n = 4)、仅通过比利时和荷兰从事人力资源管理工作的非人力资源管理人员(n = 5),或通过上述来源中的两个(n = 13)或三个(n = 16)的组合,确定了 43 项从事人力资源管理工作的非人力资源管理人员参与的任务。日志中包含的任务数量和构成每年都会根据国家监测协调中心的新见解进行调整。根据年度审查结果,在 2024 年版本中,73 项任务反映了在 RM 工作的 N&M 的扩展作用。在一些国家,有七项专业任务(如胚胎移植)由在生殖医学领域工作的 N&M 独立完成,而在其他国家,N&M 仅发挥 "协助 "作用。候选人还需就一个临床病例提交成熟的伦理反思。为了在整个认证过程中为申请人提供支持,NMCC 制定了与从事 RM 工作的 N&M 的所有任务相一致的课程:文献综述没有在咨询国际专家小组或调查比利时和荷兰从事 RM 工作的 N&M 之前完成:文献综述、国际专家小组以及接受调查的比利时和荷兰从事 RM 工作的 N&M 的任务和角色在不同国家和国家内部、诊所和个人之间存在差异,这为有组织的专业发展提供了机会。需要开展进一步研究,以了解从事 RM 工作的 N&M 在获得认证后的经历及其对专业发展的影响:H.K. 从 Gedeon Richter、Finox 和 MEDEA 获得了咨询费和酬金,并从 Gedeon Richter 和 Finox 获得了差旅费资助。其他作者声明无利益冲突:不适用。
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引用次数: 0
Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing. 单细胞 RNA 测序揭示人类睾丸老化的转录组格局和潜在靶标
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae199
Kai Xia, Peng Luo, Jiajie Yu, Siyuan He, Lin Dong, Feng Gao, Xuren Chen, Yunlin Ye, Yong Gao, Yuanchen Ma, Cuifeng Yang, Yadong Zhang, Qiyun Yang, Dayu Han, Xin Feng, Zi Wan, Hongcai Cai, Qiong Ke, Tao Wang, Weiqiang Li, Xiang'an Tu, Xiangzhou Sun, Chunhua Deng, Andy Peng Xiang
<p><strong>Study question: </strong>What is the molecular landscape underlying the functional decline of human testicular ageing?</p><p><strong>Summary answer: </strong>The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing.</p><p><strong>What is known already: </strong>Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing.</p><p><strong>Study design, size, duration: </strong>Human testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors.</p><p><strong>Participants/materials, setting, methods: </strong>scRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat.</p><p><strong>Main results and the role of chance: </strong>The single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamics in germ cells revealed that the disruption of the base-excision repair pathway is a prominent characteristic of old SSCs, suggesting that defective DNA repair in SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of ageing-associated transcriptional changes demonstrated that stress-related changes and cytokine pathways accumulate in old somatic cells. Age-related impairment of redox homeostasis in old LCs was identified and pharmacological treatment with antioxidants alleviated this cellular dysfunction of LCs and promoted testosterone production. Lastly, our results revealed that decreased pleiotrophin signalling was a contributing factor for impaired spermatogenesis in testicular ageing.</p><p><strong>Large scale data: </strong>The scRNA-seq sequencing and processed data reported in this paper were deposited at the Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under the accession number HRA002349.</p><p><strong>Limitations, reasons for caution: </strong>Owing to the difficulty in collecting human testis tissue, the sample size was limited. Further in-depth functional and mechanistic studies are warranted in future.</p><p><strong>Wider implications of the findings: </strong>These findings provide a comprehensive understanding of the cell type-specific mechanisms underlying human te
研究问题:人类睾丸老化功能衰退的分子基础是什么?本研究提供了年轻和年老人类睾丸的全面单细胞转录组图谱,为人类睾丸老化的分子机制和潜在靶点提供了见解:众所周知,睾丸老化会导致男性与年龄相关的生育能力下降和性腺功能减退。睾丸细胞功能障碍被认为是睾丸老化的关键因素:研究设计、规模和持续时间:分别从三个年轻人和三个老年人身上采集人体睾丸活检样本,进行单细胞 RNA 测序(scRNA-seq)。参与者/材料、环境、方法:利用 scRNA-seq 鉴定人类睾丸细胞在衰老过程中的基因表达特征。通过基因组富集分析法分析了精原干细胞(SSCs)和莱迪格细胞(LCs)中与衰老相关的基因表达变化,并通过免疫荧光和功能测试进行了验证。主要结果和偶然性的作用:研究人员调查了年轻男性和老年男性睾丸的单细胞转录组图谱,揭示了生殖细胞和体细胞龛细胞与年龄有关的变化。对生殖细胞基因表达动态的深入评估发现,碱基切除修复途径的破坏是老年生殖细胞的一个显著特征,这表明生殖细胞的DNA修复缺陷可能是随着年龄增长生殖突变增加的潜在驱动因素。对衰老相关转录变化的进一步分析表明,应激相关变化和细胞因子通路在老年体细胞中累积。研究还发现,衰老体细胞的氧化还原平衡受到了与年龄相关的损害,抗氧化剂的药物治疗缓解了衰老体细胞的细胞功能障碍,并促进了睾酮的产生。最后,我们的研究结果表明,多营养素信号的减少是睾丸老化过程中精子发生受损的一个因素:本文报告的scRNA-seq测序和处理数据已存入基因组序列档案(https://ngdc.cncb.ac.cn/),登录号为HRA002349。局限性和需要谨慎的原因:由于难以收集人类睾丸组织,样本量有限。研究结果的广泛影响:这些研究结果为全面了解人类睾丸组织的功能提供了依据:这些发现以单细胞分辨率提供了对人类睾丸老化的细胞类型特异性机制的全面理解,并提出了潜在的治疗靶点,可用于解决与年龄相关的男性生育能力下降和性腺功能减退问题:本研究得到了国家重点研发计划(2022YFA1104100)、国家自然科学基金(32130046, 82171564, 82101669, 82371611, 82371609, 82301796)、广东省自然科学基金(2022A1515010371)和广东省医学科技重大专项(2022A1515010371)的资助、国家卫生计生委医学科技发展研究中心重大项目(HDSL202001000)、国家卫生计生委男性生殖与遗传重点实验室开放课题(KF202001)、广东省区域联合基金-青年基金项目(2021A1515110921、2022A1515111201)、中国博士后科学基金(2021M703736)。作者声明无利益冲突。
{"title":"Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing.","authors":"Kai Xia, Peng Luo, Jiajie Yu, Siyuan He, Lin Dong, Feng Gao, Xuren Chen, Yunlin Ye, Yong Gao, Yuanchen Ma, Cuifeng Yang, Yadong Zhang, Qiyun Yang, Dayu Han, Xin Feng, Zi Wan, Hongcai Cai, Qiong Ke, Tao Wang, Weiqiang Li, Xiang'an Tu, Xiangzhou Sun, Chunhua Deng, Andy Peng Xiang","doi":"10.1093/humrep/deae199","DOIUrl":"10.1093/humrep/deae199","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the molecular landscape underlying the functional decline of human testicular ageing?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;Human testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;scRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamics in germ cells revealed that the disruption of the base-excision repair pathway is a prominent characteristic of old SSCs, suggesting that defective DNA repair in SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of ageing-associated transcriptional changes demonstrated that stress-related changes and cytokine pathways accumulate in old somatic cells. Age-related impairment of redox homeostasis in old LCs was identified and pharmacological treatment with antioxidants alleviated this cellular dysfunction of LCs and promoted testosterone production. Lastly, our results revealed that decreased pleiotrophin signalling was a contributing factor for impaired spermatogenesis in testicular ageing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;The scRNA-seq sequencing and processed data reported in this paper were deposited at the Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under the accession number HRA002349.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;Owing to the difficulty in collecting human testis tissue, the sample size was limited. Further in-depth functional and mechanistic studies are warranted in future.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;These findings provide a comprehensive understanding of the cell type-specific mechanisms underlying human te","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143053","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}
引用次数: 0
The web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial. 基于网络的 "快乐与怀孕 "计划在治疗不明原因不孕症中的应用:随机对照试验。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae220
F Dreischor, E A F Dancet, C B Lambalk, H W van Lunsen, D Besselink, J van Disseldorp, J Boxmeer, E A Brinkhuis, B J Cohlen, A Hoek, M de Hundt, C A H Janssen, M Lambers, J Maas, A Nap, D Perquin, M Verberg, H R Verhoeve, J Visser, L van der Voet, M H Mochtar, M Goddijn, E Laan, M van Wely, I M Custers
<p><strong>Study question: </strong>Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility?</p><p><strong>Summary answer: </strong>The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility.</p><p><strong>What is known already: </strong>Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial.</p><p><strong>Study design, size, duration: </strong>This is a nationwide multi-centre, unblinded, randomized controlled superiority trial (web-based randomization programme, 1:1 allocation ratio). This RCT intended to recruit 1164 couples within 3 years but was put on hold after having included 700 couples over 5 years (2016-2021). The web-based P&P programme contains psychosexual information and couple communication, mindfulness and sensate focus exercises aiming to help maintain or improve sexual health, mainly pleasure, and hence increase pregnancy rates. The P&P programme additionally offers information on the biology of conception and enables couples to interact online with peers and via email with coaches.</p><p><strong>Participants/materials, setting, methods: </strong>Heterosexual couples with unexplained infertility and a Hunault-prognosis of at least 30% chance of naturally conceiving a live-born child within 12 months were included, after their diagnostic work-up in 41 Dutch secondary and tertiary fertility centres. The primary outcome was an ongoing pregnancy, defined as a viable intrauterine pregnancy of at least 12 weeks duration confirmed by an ultrasound scan, conceived naturally within 6 months after randomization. Secondary outcomes were time to pregnancy, live birth, sexual health, and personal and relational well-being at baseline and after 3 and 6 months. The primary analyses were according to intention-to-treat principles. We calculated relative risks (RRs, pregnancy rates) and a risk difference (RD, pregnancy rates), Kaplan-Meier survival curves (live birth over time), and time, group, and interactive effects with mixed models analyses (sexual health and well-being).</p><p><strong>Main results and the role of chance: </strong>Totals of 352 (one withdrawal) and 348 (three withdrawals) couples were allocated to, respectively the P&P group and the expectant management group. Web-based tracking of the intervention group showed a high attrition rate (57% of couples) and limited engagement (i.e. median of 16 visits and 33 min total visitation time per couple). Intention-to-treat analyses showed that 19.4% (n = 68/351) of the P&P group and 22.6% (n = 78/345) of the expectant management group achieved a naturally conceived ongoing pregnancy (RR = 0.86; 95% CI = 0.64-1.15, RD = -3.24%; 95% CI -9.28 t
研究问题:提供 "快乐怀孕"(P&P)计划而非预期管理是否能提高被诊断为不明原因不孕症夫妇的自然怀孕率?P&P计划对不明原因不孕症夫妇的持续怀孕率没有影响:研究表明,针对性健康的面对面干预可能会提高怀孕率。研究的设计、规模和持续时间:这是一项全国范围的多中心、无盲、随机对照优效试验(基于网络的随机方案,1:1 分配比例)。该 RCT 原计划在 3 年内招募 1164 对夫妇,但在 5 年内(2016-2021 年)招募了 700 对夫妇后被搁置。基于网络的 P&P 计划包含性心理信息和夫妻沟通、正念和感觉集中练习,旨在帮助维持或改善性健康,主要是性快感,从而提高怀孕率。此外,P&P 计划还提供了受孕生物学方面的信息,并使夫妇能够在线与同伴互动,或通过电子邮件与教练互动。参与者/材料、环境、方法:41 家荷兰二级和三级生殖中心对不明原因不孕症夫妇进行诊断后,将他们纳入其中,并预测他们在 12 个月内自然怀上活产婴儿的几率至少为 30%。主要结果是持续妊娠,即经超声波扫描确认的至少12周的宫内存活妊娠,并在随机化后6个月内自然受孕。次要结果是怀孕时间、活产率、性健康以及基线和 3 个月及 6 个月后的个人和关系幸福感。主要分析遵循意向治疗原则。我们计算了相对风险(RRs,怀孕率)和风险差异(RD,怀孕率)、卡普兰-米尔生存曲线(活产时间)以及混合模型分析的时间、组别和交互效应(性健康和幸福感):共有 352 对(退出 1 对)和 348 对(退出 3 对)夫妇分别被分配到 P&P 组和预期管理组。对干预组的网络跟踪显示,该组的减员率较高(57%的夫妇),参与度有限(即每对夫妇的访问次数中位数为 16 次,总访问时间为 33 分钟)。意向治疗分析显示,19.4% 的 P&P 组(n = 68/351)和 22.6%的预期管理组(n = 78/345)实现了自然受孕(RR = 0.86;95% CI = 0.64-1.15,RD = -3.24%;95% CI -9.28-2.81)。两组的怀孕时间没有差异(对数等级 = 0.23)。P&P组中有18.8%的夫妇(n = 66/351)生下了活产儿,而预期管理组中有22.3%的夫妇(n = 77/345)生下了活产儿(RR = 0.84; 95% CI = 0.63-1.1)。随着时间的推移,两组的性交频率同样有所下降。P&P组女性的性快感、性高潮和满意度有所提高,而预期管理组的这些结果保持稳定。男性的性高潮、性交满意度和总体满意度则随着时间的推移而下降,组间没有差异。干预措施没有影响个人和人际关系的幸福感。在整个研究人群中,因过早开始医学辅助生殖而导致的不依从率和临床随访损失率分别为15.1%和1.4%。按方案进行的主要结果分析表明,两组之间没有差异。将参与度最高的使用者与预期管理组进行比较后发现,干预组的同房频率下降较少,男性性欲有所提高:由于招募速度较慢,未能达到 1164 个样本的预期规模。然而,已达到的样本量足够大,足以排除P&P计划对我们的主要结果有超过8%的改善:研究结果的广泛影响:P&P 计划不应该用来提高自然怀孕率,但可以考虑用来改善性健康。P&P项目的自然减员和有限参与与其他电子健康项目的研究结果一致,并强调了用户体验研究的重要性:由荷兰卫生研究与发展组织(ZonMw,编号:843001605)和佛兰德斯研究基金会资助。C.B.L. 是《人类生殖》杂志的主编。H.W.L. 从 Prometheus Publishers Springer Media Thieme Verlag 获得版税或许可证。J.B.
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引用次数: 0
Testing an artificial intelligence algorithm to predict fetal heartbeat of vitrified-warmed blastocysts from a single image: predictive ability in different settings. 测试从单张图像预测玻璃化温育囊胚胎儿心跳的人工智能算法:不同环境下的预测能力。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae178
L Conversa, L Bori, F Insua, S Marqueño, A Cobo, M Meseguer
<p><strong>Study question: </strong>Could an artificial intelligence (AI) algorithm predict fetal heartbeat from images of vitrified-warmed embryos?</p><p><strong>Summary answer: </strong>Applying AI to vitrified-warmed blastocysts may help predict which ones will result in implantation failure early enough to thaw another.</p><p><strong>What is known already: </strong>The application of AI in the field of embryology has already proven effective in assessing the quality of fresh embryos. Therefore, it could also be useful to predict the outcome of frozen embryo transfers, some of which do not recover their pre-vitrification volume, collapse, or degenerate after warming without prior evidence.</p><p><strong>Study design, size, duration: </strong>This retrospective cohort study included 1109 embryos from 792 patients. Of these, 568 were vitrified blastocysts cultured in time-lapse systems in the period between warming and transfer, from February 2022 to July 2023. The other 541 were fresh-transferred blastocysts serving as controls.</p><p><strong>Participants/materials, setting, methods: </strong>Four types of time-lapse images were collected: last frame of development of 541 fresh-transferred blastocysts (FTi), last frame of 467 blastocysts to be vitrified (PVi), first frame post-warming of 568 vitrified embryos (PW1i), and last frame post-warming of 568 vitrified embryos (PW2i). After providing the images to the AI algorithm, the returned scores were compared with the conventional morphology and fetal heartbeat outcomes of the transferred embryos (n = 1098). The contribution of the AI score to fetal heartbeat was analyzed by multivariate logistic regression in different patient populations, and the predictive ability of the models was measured by calculating the area under the receiver-operating characteristic curve (ROC-AUC).</p><p><strong>Main results and the role of chance: </strong>Fetal heartbeat rate was related to AI score from FTi (P < 0.001), PW1i (P < 0.05), and PW2i (P < 0.001) images. The contribution of AI score to fetal heartbeat was significant in the oocyte donation program for PW2i (odds ratio (OR)=1.13; 95% CI [1.04-1.23]; P < 0.01), and in cycles with autologous oocytes for PW1i (OR = 1.18; 95% CI [1.01-1.38]; P < 0.05) and PW2i (OR = 1.15; 95% CI [1.02-1.30]; P < 0.05), but was not significantly associated with fetal heartbeat in genetically analyzed embryos. AI scores from the four groups of images varied according to morphological category (P < 0.001). The PW2i score differed in collapsed, non-re-expanded, or non-viable embryos compared to normal/viable embryos (P < 0.001). The predictability of the AI score was optimal at a post-warming incubation time of 3.3-4 h (AUC = 0.673).</p><p><strong>Limitations, reasons for caution: </strong>The algorithm was designed to assess fresh embryos prior to vitrification, but not thawed ones, so this study should be considered an external trial.</p><p><strong>Wider implications of the fin
研究问题:人工智能(AI)算法能否从玻璃化温育胚胎的图像中预测胎儿心跳?将人工智能应用于玻璃化温育囊胚可能有助于预测哪些囊胚会导致植入失败,从而及早解冻另一个囊胚:已知信息:人工智能在胚胎学领域的应用已被证明能有效评估新鲜胚胎的质量。因此,人工智能也可用于预测冷冻胚胎移植的结果,因为有些冷冻胚胎在没有事先证据的情况下无法恢复玻璃化前的体积、塌陷或在升温后退化:这项回顾性队列研究包括来自 792 名患者的 1109 枚胚胎。其中,568 个胚胎是在 2022 年 2 月至 2023 年 7 月的升温和移植之间的时间延迟系统中培养的玻璃化囊胚。参与者/材料、环境、方法:收集了四种类型的延时图像:541 个新鲜移植囊胚发育的最后一帧(FTi)、467 个即将玻璃化的囊胚的最后一帧(PVi)、568 个玻璃化胚胎升温后的第一帧(PW1i)和 568 个玻璃化胚胎升温后的最后一帧(PW2i)。向人工智能算法提供图像后,将返回的评分与移植胚胎(n = 1098)的常规形态学和胎心搏动结果进行比较。通过多变量逻辑回归分析了不同患者群体中人工智能评分对胎心率的贡献,并通过计算接收者操作特征曲线下面积(ROC-AUC)衡量了模型的预测能力:主要结果和偶然性的作用:胎心率与 FTi 的 AI 评分相关(P 局限性、需谨慎的原因):该算法旨在评估玻璃化前的新鲜胚胎,而非解冻胚胎,因此本研究应被视为一项外部试验:研究结果的广泛意义:预测软件在冷冻胚胎移植管理中的应用对胚胎学家来说可能是一个有用的工具,可降低囊胚不能从玻璃化中恢复的周期的取消率。具体来说,本研究中测试的算法既可用于评估配备延时系统的诊所解冻的胚胎,也可用于评估仅配备传统培养箱的诊所解冻的胚胎,因为只需拍摄一张照片即可:本研究得到了巴伦西亚大区创新、大学、科学和数字社会部(CIACIF/2021/019)和卡洛斯三世健康研究所(PI21/00283)的支持,以及欧盟(ERDF,"A way to make Europe")的共同资助。在过去 5 年中,M.M. 从 Merck、Vitrolife、MSD、Ferring、AIVF、Theramex、Gedeon Richter、Genea Biomedx 和 Life Whisperer 处获得个人讲课酬金。没有其他利益冲突。试验注册号:不适用。
{"title":"Testing an artificial intelligence algorithm to predict fetal heartbeat of vitrified-warmed blastocysts from a single image: predictive ability in different settings.","authors":"L Conversa, L Bori, F Insua, S Marqueño, A Cobo, M Meseguer","doi":"10.1093/humrep/deae178","DOIUrl":"10.1093/humrep/deae178","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Could an artificial intelligence (AI) algorithm predict fetal heartbeat from images of vitrified-warmed embryos?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Applying AI to vitrified-warmed blastocysts may help predict which ones will result in implantation failure early enough to thaw another.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The application of AI in the field of embryology has already proven effective in assessing the quality of fresh embryos. Therefore, it could also be useful to predict the outcome of frozen embryo transfers, some of which do not recover their pre-vitrification volume, collapse, or degenerate after warming without prior evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This retrospective cohort study included 1109 embryos from 792 patients. Of these, 568 were vitrified blastocysts cultured in time-lapse systems in the period between warming and transfer, from February 2022 to July 2023. The other 541 were fresh-transferred blastocysts serving as controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Four types of time-lapse images were collected: last frame of development of 541 fresh-transferred blastocysts (FTi), last frame of 467 blastocysts to be vitrified (PVi), first frame post-warming of 568 vitrified embryos (PW1i), and last frame post-warming of 568 vitrified embryos (PW2i). After providing the images to the AI algorithm, the returned scores were compared with the conventional morphology and fetal heartbeat outcomes of the transferred embryos (n = 1098). The contribution of the AI score to fetal heartbeat was analyzed by multivariate logistic regression in different patient populations, and the predictive ability of the models was measured by calculating the area under the receiver-operating characteristic curve (ROC-AUC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Fetal heartbeat rate was related to AI score from FTi (P &lt; 0.001), PW1i (P &lt; 0.05), and PW2i (P &lt; 0.001) images. The contribution of AI score to fetal heartbeat was significant in the oocyte donation program for PW2i (odds ratio (OR)=1.13; 95% CI [1.04-1.23]; P &lt; 0.01), and in cycles with autologous oocytes for PW1i (OR = 1.18; 95% CI [1.01-1.38]; P &lt; 0.05) and PW2i (OR = 1.15; 95% CI [1.02-1.30]; P &lt; 0.05), but was not significantly associated with fetal heartbeat in genetically analyzed embryos. AI scores from the four groups of images varied according to morphological category (P &lt; 0.001). The PW2i score differed in collapsed, non-re-expanded, or non-viable embryos compared to normal/viable embryos (P &lt; 0.001). The predictability of the AI score was optimal at a post-warming incubation time of 3.3-4 h (AUC = 0.673).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;The algorithm was designed to assess fresh embryos prior to vitrification, but not thawed ones, so this study should be considered an external trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the fin","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035677","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}
引用次数: 0
Reply. Recurrent implantation failure in patients undergoing euploid embryo transfers are unlikely to be caused by unmodifiable extra-embryonic factors. 回复。接受优倍体胚胎移植的患者反复种植失败的原因不太可能是不可改变的胚外因素。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae185
Baris Ata, Pavan Gill, Danilo Cimadomo, Filippo Maria Ubaldi, Juan A Garcia-Velasco, Emre Seli
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引用次数: 0
Distribution of endometriosis phenotypes according to patients' age in adult women with surgical evaluation. 接受手术评估的成年女性子宫内膜异位症表型的年龄分布。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae180
M Bourdon, C Maignien, L Marcellin, L Maitrot Mantelet, G Parpex, P Santulli, C Chapron
<p><strong>Study question: </strong>What is the distribution of endometriosis phenotypes according to age in adult women undergoing surgery?</p><p><strong>Summary answer: </strong>The phenotype of endometriosis did not significantly vary after 24 years old.</p><p><strong>What is known already: </strong>The phenotypic evolution of endometriosis over time remains unclear. While adolescents can exhibit any type of endometriosis lesions, ovarian endometriosis (OMA) and/or deep-infiltrating endometriosis (DIE) tend to increase with age in young adults. In adulthood, understanding the evolution of lesions is crucial for disease management, but the literature on this subject is limited. This study aims to examine the distribution of endometriosis phenotypes in relation to age among adult patients requiring surgical treatment.</p><p><strong>Study design, size, duration: </strong>This observational cohort study included patients aged between ≥18 and ≤42 years, who underwent surgery for benign gynecological conditions at our institution between January 2004 and December 2022. A standardized questionnaire was completed for each patient during a face-to-face interview conducted by the surgeon in the month preceding surgery. Women with histologically proven endometriosis were included.</p><p><strong>Participants/materials, setting, methods: </strong>The distribution of endometriosis phenotypes (isolated superficial (SUP) endometriosis, OMA ± SUP, DIE ± SUP/OMA) was compared between young adults (≤24 years) and adults (>24 years) and among adults (25-28 years, 29-33 years, 34-38 years, 39 to ≤42 years) using univariate and multivariate analysis. The distribution of different subtypes of DIE (uterosacral ligament(s), vagina, bladder, intestine, and ureter), OMA size, and intensity of pain symptoms were also examined.</p><p><strong>Main results and the role of chance: </strong>A total of 1311 adult women with histologically proven endometriosis were included. In women aged 24 years or younger (n = 116), the distribution of endometriosis phenotypes differed significantly from women older than 24 years (n = 1195): The frequency of the DIE ± SUP/OMA phenotype was lower (41.4% versus 56.1%, respectively), while the rate of isolated superficial lesions was higher (from 32.0% versus 25.9%) (P = 0.001). In the group of women aged >24 years, a significantly higher proportion of vaginal DIE lesions (P = 0.012) and a lower proportion of uterosacral ligament DIE lesions (P = 0.004) were found compared to women aged ≤24 years. No significant differences were observed in terms of endometrioma size. Between the ages of 25 and 42 years, there were no significant changes in the distribution of endometriosis phenotypes after univariate and multivariate analysis. The distribution of subtype of DIE lesions did not significantly change with age between 25 and 42 years. Concerning pain symptom scores, there was a significant decrease with age for dysmenorrhea and dyspareunia.</p><p>
研究问题:在接受手术的成年女性中,子宫内膜异位症表型在不同年龄段的分布情况如何?24岁之后,子宫内膜异位症的表型没有明显变化:子宫内膜异位症的表型随时间的演变仍不清楚。虽然青少年可以表现出任何类型的子宫内膜异位症病变,但卵巢子宫内膜异位症(OMA)和/或深部浸润性子宫内膜异位症(DIE)往往会随着年龄的增长而增加。成年后,了解病变的演变对疾病的治疗至关重要,但这方面的文献却很有限。本研究旨在探讨需要手术治疗的成年患者中,子宫内膜异位症表型的分布与年龄的关系:这项观察性队列研究纳入了2004年1月至2022年12月期间在我院接受良性妇科疾病手术治疗的年龄≥18岁至≤42岁的患者。每位患者在手术前一个月由外科医生进行的面对面访谈中都填写了一份标准化问卷。经组织学证实患有子宫内膜异位症的妇女也包括在内:通过单变量和多变量分析,比较了青壮年(≤24 岁)和成年人(>24 岁)之间以及成年人(25-28 岁、29-33 岁、34-38 岁、39 至≤42 岁)之间子宫内膜异位症表型(孤立性浅表(SUP)子宫内膜异位症、OMA ± SUP、DIE ± SUP/OMA)的分布情况。此外,还研究了不同亚型 DIE(子宫骶骨韧带、阴道、膀胱、肠道和输尿管)、OMA 大小和疼痛症状强度的分布情况:共纳入了 1311 名经组织学证实患有子宫内膜异位症的成年女性。在 24 岁或以下的女性中(n = 116),子宫内膜异位症表型的分布与 24 岁以上的女性(n = 1195)有显著差异:DIE ± SUP/OMA 表型的发生率较低(分别为 41.4% 和 56.1%),而孤立表层病变的发生率较高(分别为 32.0% 和 25.9%)(P = 0.001)。在年龄大于 24 岁的妇女组中,阴道 DIE 病变的比例明显高于年龄小于 24 岁的妇女(P = 0.012),而子宫骶骨韧带 DIE 病变的比例则低于年龄小于 24 岁的妇女(P = 0.004)。子宫内膜瘤的大小没有明显差异。经过单变量和多变量分析,25 至 42 岁女性的子宫内膜异位症表型分布无明显变化。在 25 至 42 岁之间,DIE 病变亚型的分布也没有随着年龄的增长而发生明显变化。在疼痛症状评分方面,痛经和性生活障碍的评分随着年龄的增长而明显下降:仅纳入手术患者可能会造成选择偏差。研究结果的广泛意义:本研究强调,成年女性的子宫内膜异位症表现并不会随着年龄的增长而改变。有必要进一步研究子宫内膜异位症的表型演变,以帮助医生做出临床决策和治疗策略:无声明:不适用。
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引用次数: 0
Mitochondria as therapeutic targets in assisted reproduction. 将线粒体作为辅助生殖的治疗目标。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae170
Raziye Melike Yildirim, Emre Seli

Mitochondria are essential organelles with specialized functions, which play crucial roles in energy production, calcium homeostasis, and programmed cell death. In oocytes, mitochondrial populations are inherited maternally and are vital for developmental competence. Dysfunction in mitochondrial quality control mechanisms can lead to reproductive failure. Due to their central role in oocyte and embryo development, mitochondria have been investigated as potential diagnostic and therapeutic targets in assisted reproduction. Pharmacological agents that target mitochondrial function and show promise in improving assisted reproduction outcomes include antioxidant coenzyme Q10 and mitoquinone, mammalian target of rapamycin signaling pathway inhibitor rapamycin, and nicotinamide mononucleotide. Mitochondrial replacement therapies (MRTs) offer solutions for infertility and mitochondrial disorders. Autologous germline mitochondrial energy transfer initially showed promise but failed to demonstrate significant benefits in clinical trials. Maternal spindle transfer (MST) and pronuclear transfer hold potential for preventing mitochondrial disease transmission and improving oocyte quality. Clinical trials of MST have shown promising outcomes, but larger studies are needed to confirm safety and efficacy. However, ethical and legislative challenges complicate the widespread implementation of MRTs.

线粒体是具有特殊功能的重要细胞器,在能量生产、钙平衡和细胞程序性死亡中发挥着至关重要的作用。在卵母细胞中,线粒体群由母体遗传,对发育能力至关重要。线粒体质量控制机制的功能障碍可导致生殖失败。由于线粒体在卵母细胞和胚胎发育中的核心作用,线粒体已被研究为辅助生殖的潜在诊断和治疗目标。针对线粒体功能并有望改善辅助生殖结果的药剂包括抗氧化剂辅酶 Q10 和线粒体醌、哺乳动物雷帕霉素靶信号通路抑制剂雷帕霉素和烟酰胺单核苷酸。线粒体替代疗法(MRT)为不孕症和线粒体疾病提供了解决方案。自体种系线粒体能量转移最初显示出前景,但在临床试验中未能显示出显著疗效。母体纺锤体转移(MST)和原核转移在预防线粒体疾病传播和提高卵母细胞质量方面具有潜力。母体纺锤体转移的临床试验显示了良好的效果,但还需要更大规模的研究来确认其安全性和有效性。然而,伦理和立法方面的挑战使 MRT 的广泛实施复杂化。
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引用次数: 0
Doppler ultrasound and first trimester pregnancy: not always a happy marriage. 多普勒超声和怀孕头三个月:并不总是幸福的婚姻。
IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-01 DOI: 10.1093/humrep/deae176
Stefania Carlucci, Christoph Lees, Piero Miloro, Ioannis Papastefanou, Gail Ter Haar, Andrea Dall'Asta
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引用次数: 0
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Human reproduction
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