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。
{"title":"Mitochondria as determinants of reproductive senescence and competence: implications for diagnosis of embryo competence in assisted reproduction.","authors":"Raziye Melike Yildirim, Emre Seli","doi":"10.1093/humrep/deae171","DOIUrl":"10.1093/humrep/deae171","url":null,"abstract":"<p><p>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.</p>","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":"141765932","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":"Reply. Exploring the impact of fertility-preserving treatment on pregnancy: key issues in patients with endometrial cancer and atypical hyperplasia.","authors":"Radostina Vasileva, Martin Koskas","doi":"10.1093/humrep/deae188","DOIUrl":"10.1093/humrep/deae188","url":null,"abstract":"","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":"142035675","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}
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
{"title":"Empowering nurses and midwives: the evidence-base for the Nurses and Midwives Certification Programme of ESHRE†.","authors":"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","doi":"10.1093/humrep/deae175","DOIUrl":"10.1093/humrep/deae175","url":null,"abstract":"<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","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/PMC11447058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092812","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}
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
{"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":"<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","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}
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
{"title":"The web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial.","authors":"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","doi":"10.1093/humrep/deae220","DOIUrl":"https://doi.org/10.1093/humrep/deae220","url":null,"abstract":"<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","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":"142365083","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}
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":"<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","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}
Baris Ata, Pavan Gill, Danilo Cimadomo, Filippo Maria Ubaldi, Juan A Garcia-Velasco, Emre Seli
{"title":"Reply. Recurrent implantation failure in patients undergoing euploid embryo transfers are unlikely to be caused by unmodifiable extra-embryonic factors.","authors":"Baris Ata, Pavan Gill, Danilo Cimadomo, Filippo Maria Ubaldi, Juan A Garcia-Velasco, Emre Seli","doi":"10.1093/humrep/deae185","DOIUrl":"10.1093/humrep/deae185","url":null,"abstract":"","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":"142035676","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}
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>
{"title":"Distribution of endometriosis phenotypes according to patients' age in adult women with surgical evaluation.","authors":"M Bourdon, C Maignien, L Marcellin, L Maitrot Mantelet, G Parpex, P Santulli, C Chapron","doi":"10.1093/humrep/deae180","DOIUrl":"10.1093/humrep/deae180","url":null,"abstract":"<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>","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":"142072636","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}
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.
{"title":"Mitochondria as therapeutic targets in assisted reproduction.","authors":"Raziye Melike Yildirim, Emre Seli","doi":"10.1093/humrep/deae170","DOIUrl":"10.1093/humrep/deae170","url":null,"abstract":"<p><p>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.</p>","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":"141765933","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}
Stefania Carlucci, Christoph Lees, Piero Miloro, Ioannis Papastefanou, Gail Ter Haar, Andrea Dall'Asta
{"title":"Doppler ultrasound and first trimester pregnancy: not always a happy marriage.","authors":"Stefania Carlucci, Christoph Lees, Piero Miloro, Ioannis Papastefanou, Gail Ter Haar, Andrea Dall'Asta","doi":"10.1093/humrep/deae176","DOIUrl":"10.1093/humrep/deae176","url":null,"abstract":"","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":"142046615","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}