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Recommendations from the WHO guideline for the prevention, diagnosis, and treatment of infertility†. 世卫组织预防、诊断和治疗不孕症指南的建议。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-01-01 DOI: 10.1093/humrep/deaf212
Gitau Mburu, Nancy Santesso, Romina Brignardello-Petersen, Richard Kennedy, Cynthia Farquhar, Jacky Boivin, Guido Pennings, Linda C Giudice, Robert W Rebar, Luca Gianaroli, Lan N Vuong, Sandro C Esteves, Christopher J De Jonge, Allan Pacey, Willem Ombelet, Tansu Kucuk, Barbara L Collura, Klaudija Kordic, Paula Amato, Thabo Matsaseng, James Kiarie
<p><strong>Study question: </strong>What is the recommended prevention, diagnosis, and treatment of infertility among individuals and couples?</p><p><strong>Summary answer: </strong>The World Health Organization (WHO) made 40 recommendations and six good practice statements for the prevention, diagnosis, and treatment of infertility.</p><p><strong>What is known already: </strong>The field of sexual and reproductive health care, including family planning has progressed in the last several decades. Significant progress has also been made in the field of medically assisted reproduction. Globally, one in six people experience infertility in their lifetime. However, many countries do not include the prevention, diagnosis, and treatment of infertility in health policies, financing, and services, and many do not have national clinical guidelines for the prevention, diagnosis, and treatment of infertility.</p><p><strong>Study design, size, duration: </strong>The guideline was developed according to the WHO handbook for guideline development. A Guideline Development Group (GDG) was assembled and included a multidisciplinary and regionally diverse set of clinicians, policymakers, researchers, implementers, and representatives of patient groups (n=30). The GDG prioritized key recommendation questions to address in the guideline.</p><p><strong>Participants/materials, setting, methods: </strong>New systematic reviews were conducted, or existing reviews updated, to inform the recommendations. The GRADE approach was used to assess the certainty of the evidence and to guide the formulation of recommendations. The GDG interpreted evidence and made judgments about the balance between benefits and harms (including patients' values) as well as costs, feasibility, acceptability, and equity. The recommendations were drafted, reviewed by an External Review Group (ERG) comprising 30 members, and approved by the WHO.</p><p><strong>Main results and the role of chance: </strong>The guideline makes good practice statements related to the general management of infertility (n = 6) including (i) selection of tests, (ii) listening to individuals and couples with infertility, (iii) choosing treatment decisions, (iv) clinical follow-up, and (v) documenting outcomes of treatment. In relation to prevention, it provides recommendations related to the provision of information about fertility and infertility (n = 1) and reduction of infertility risk from sexually transmitted infections (STIs; n = 1), lifestyle factors (n = 1), and tobacco use (n = 1). In terms of diagnosis, recommendations for diagnosing infertility caused by ovulatory dysfunction (n = 3), tubal disease (n = 1), or uterine cavity abnormalities (n = 5) among females are provided. For males, the guideline provides recommendations regarding when a semen test should be repeated (n = 2). Also included is a recommendation for diagnosing unexplained infertility (n = 1). Regarding treatment, the guideline provides recommendat
研究问题:个人和夫妇之间推荐的预防、诊断和治疗不孕症是什么?摘要回答:世界卫生组织(世卫组织)就预防、诊断和治疗不孕症提出了40项建议和6项良好做法声明。已知情况:包括计划生育在内的性保健和生殖保健领域在过去几十年中取得了进展。在医疗辅助生殖领域也取得了重大进展。在全球范围内,六分之一的人一生中会经历不孕症。然而,许多国家没有将不孕症的预防、诊断和治疗纳入卫生政策、筹资和服务,许多国家没有预防、诊断和治疗不孕症的国家临床指南。研究设计、规模、持续时间:本指南根据世卫组织指南制定手册制定。指南制定小组(GDG)由多学科和地区不同的临床医生、政策制定者、研究人员、实施者和患者群体代表组成(n=30)。GDG在指南中优先考虑了需要解决的关键建议问题。参与者/材料、环境、方法:进行新的系统评价,或更新现有评价,以告知建议。GRADE方法用于评估证据的确定性并指导建议的制定。GDG解释证据并对利弊(包括患者的价值观)以及成本、可行性、可接受性和公平性之间的平衡做出判断。这些建议由一个由30名成员组成的外部审查小组(ERG)起草和审查,并由世卫组织批准。主要结果和偶然性的作用:该指南对不孕症的一般管理(n = 6)作出了良好做法声明,包括(i)选择检查,(ii)听取不孕症个人和夫妇的意见,(iii)选择治疗决定,(iv)临床随访,(v)记录治疗结果。在预防方面,它提供了有关提供生育和不孕症信息(n = 1)以及减少性传播感染(STIs; n = 1)、生活方式因素(n = 1)和烟草使用(n = 1)的不孕症风险的建议。在诊断方面,建议诊断女性因排卵功能障碍(n = 3)、输卵管疾病(n = 1)或子宫腔异常(n = 5)引起的不孕症。对于男性,该指南提供了关于何时应重复精液检测的建议(n = 2)。还包括诊断不明原因不孕症的建议(n = 1)。在治疗方面,指南提供了与多囊卵巢综合征(n = 6)、输卵管疾病(n = 5)、子宫间隔(n = 1)、精索静脉曲张(n = 4)和不明原因不孕症(n = 6)的治疗相关的建议。根据现有的证据,GDG并没有对男性使用抗氧化剂补充剂提出建议。大多数建议都是有条件的,因为相关证据要么缺乏,要么确定性很低或很低。确定了关键的研究空白。局限性,谨慎的原因:这些建议并没有涵盖不孕症和生育护理的所有方面,但指南的后续版本将扩大建议的范围。研究结果的更广泛影响:该指南以公平、科学和提供生育护理作为全民健康覆盖一部分的必要性为中心,旨在支持各国为所有人提供高质量、公平和有效的医疗保健。虽然该指南主要供卫生保健专业人员使用,但它也是决策者为国家指南提供信息和为专业患者支持工作提供信息的重要来源,包括宣传组织、供资和慈善机构、民间社会、专业协会和为生殖健康规划提供社会、财政和技术支持的其他非政府组织。研究经费/竞争利益:这项工作得到了开发计划署-人口基金-儿童基金会-卫生组织-世界银行人类生殖研究、发展和研究培训特别方案的经费,这是一个由世界卫生组织(卫生组织)执行的共同赞助方案。所有指定作者的权益申报详情载于补充表S1,未指定作者的政府工作小组成员的权益申报详情载于补充表S2,而政府工作小组成员的权益申报详情载于补充表S3。试验注册号:无。免责声明:这份手稿报告了来自世卫组织指南的建议摘要。世卫组织已采取一切合理预防措施来核实指南出版物中包含的信息。 然而,发布的材料没有任何形式的保证,无论是明示的还是暗示的。
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Automated oocyte retrieval, denudation, sperm preparation, and ICSI in the IVF laboratory: a proof-of-concept study and report of the first live births. 体外受精实验室中的自动卵母细胞提取、剥脱、精子制备和ICSI:一项概念验证研究和首次活产报告。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-26 DOI: 10.1093/humrep/deaf240
A Chavez-Badiola,G Mendizabal-Ruiz,A Flores-Saiffe Farías,N Costa-Borges,A Murray,M Alikani,G Silvestri,C Millan,E Hernández-Morales,R Valencia-Murillo,V Medina,E Mestres,A Valadez Aguilar,V Ocegueda-Hernández,F Acosta-Gómez,A Álvarez López,M Acacio,Q Matia-Algué,J G Espinoza Figueroa,L M Campos Olmedo,C P Barragan,D J Sánchez-González,J Cohen
STUDY QUESTIONCan multiple automated systems sequentially perform Day 0 IVF procedures: (i) sperm preparation, (ii) cumulus-oocyte complex (COC) retrieval and oocyte denudation, and (iii) ICSI?SUMMARY ANSWERAutomated sequential Day 0 procedures achieved fertilization in 64.3% of injected oocytes and 42.2% usable blastocyst formation in 11 cases, resulting in five healthy live births from nine patients with positive pregnancy tests.WHAT IS KNOWN ALREADYThe Day 0 procedures-sperm preparation, oocyte handling (e.g. finding and denudation), and ICSI-rely on embryologist skill. Automation in IVF laboratories has the potential to improve reproducibility, yet its implementation remains limited. Fully automated pipetting workflows replicating embryologist activities have not yet been achieved, though partial automation of key steps such as dish preparation and ICSI has been reported.STUDY DESIGN, SIZE, DURATIONProof-of-concept pilot study with prospective allocation of sibling oocytes to automated or manual protocols. Here, we report on Day 0 automation in 11 cases using two or three automated systems (nicknamed 'pearls') in sequence. Single vitrified/warmed blastocyst transfers occurred between April and October 2024. This work was part of a larger research programme evaluating automation across multiple IVF laboratory procedures from gamete handling through blastocyst transfer and specifically demonstrates sequential automation across multiple Day 0 procedures within a single workflow.PARTICIPANTS/MATERIALS, SETTING, METHODSEleven consenting patients (three autologous, eight donor egg cycles) underwent IVF/ICSI following minimal or mild stimulation. The gametes were processed using either automated or manual protocols. The automated systems-Pearl 1 (sperm preparation), Pearl 2 (COC retrieval and oocyte denudation), and Pearl 3 (sperm selection, laser immobilization, and piezo-ICSI)-were used in various combinations. Multiple AIs were developed and deployed across these systems. This IRB-approved study was conducted at Hope IVF, Guadalajara, México.MAIN RESULTS AND THE ROLE OF CHANCEThe automated systems achieved 64.3% fertilization (45/70) and 42.2% usable blastocyst formation per zygote (19/45), compared to 81% (47/58) and 59.6% (28/47) with manual procedures. Transfers from the automated arm resulted in five live births, three biochemical pregnancies, and one early loss at 7 weeks. The live birth rate per transfer of a single warmed blastocyst in the automated arm was 5/12 (41.7%).LIMITATIONS, REASONS FOR CAUTIONThe small sample size prevented statistical comparison between automated and manual procedures. Some steps required operator support via direct intervention or digital control. Autonomy (defined as automated execution without human intervention) was achieved only in sperm preparation and selected ICSI tasks. A larger study using an updated system is underway.WIDER IMPLICATIONS OF THE FINDINGSThis study demonstrates the feasibility of automati
研究问题:多个自动化系统能否依次执行第0天试管婴儿程序:(i)精子准备,(ii)卵丘-卵母细胞复合体(COC)检索和卵母细胞剥离,以及(iii) ICSI?自动顺序第0天程序在11例中实现了64.3%的注射卵母细胞受精率和42.2%的可用囊胚形成率,使9例妊娠试验阳性患者的5例健康活产。第0天的程序——精子准备、卵母细胞处理(如发现和剥脱)和icsi——依赖于胚胎学家的技能。试管婴儿实验室的自动化有可能提高可重复性,但其实施仍然有限。完全自动化的移液工作流程复制胚胎学家的活动尚未实现,尽管部分自动化的关键步骤,如培养皿准备和ICSI已被报道。研究设计、规模、持续时间对同胞卵母细胞进行自动或手动分配的前瞻性概念验证试点研究。在这里,我们报告了11个使用两个或三个自动化系统(昵称为“珍珠”)的第0天自动化案例。单个玻璃化/加热囊胚移植发生于2024年4月至10月。这项工作是一个更大的研究项目的一部分,该项目评估了从配子处理到囊胚转移的多个试管婴儿实验室程序的自动化,并特别展示了在单个工作流程中多个Day 0程序的顺序自动化。参与者/材料、环境、方法:即使是同意的患者(3个自体,8个供体卵子周期)在轻微或轻度刺激后接受IVF/ICSI。配子的处理可采用自动或手动方法。自动化系统Pearl 1(精子制备),Pearl 2 (COC提取和卵母细胞剥离)和Pearl 3(精子选择,激光固定和压电icsi)以各种组合使用。在这些系统中开发和部署了多个ai。这项irb批准的研究是在墨西哥瓜达拉哈拉的Hope IVF进行的。自动化系统的受精率为64.3%(45/70),每个受精卵的可用囊胚形成率为42.2%(19/45),而人工系统的受精率为81%(47/58)和59.6%(28/47)。从自动手臂转移的结果是5例活产,3例生化妊娠,1例7周早期流产。单个受热囊胚在自动臂内每次移植的活产率为5/12(41.7%)。局限性和注意原因小样本量妨碍了自动和手动程序之间的统计比较。有些步骤需要操作员通过直接干预或数字控制来支持。自主性(定义为无需人工干预的自动执行)仅在精子准备和选定的ICSI任务中实现。一项使用更新系统的更大规模研究正在进行中。研究结果的广泛意义本研究证明了自动化第0天试管婴儿程序的可行性,具有提高标准化和减少方案漂移、疲劳和操作人员可变性的潜力。我们的研究结果支持分阶段集成自动化以满足不断增长的ART需求。研究经费/竞争利益(S)本研究由imagine Life Sciences赞助。A.C.-B。他是imagine Life Sciences的员工、股东和公司官员,也持有IVF 2.0的股份。G.M.-R。他是imagine Life Sciences的股票期权持有人,并获得了imagine Life Sciences和IVF 2.0的咨询费。aff - s.f.是想象生命科学公司的雇员和股票期权持有人。N.C.-B。他是imagine Life Sciences的股票期权持有人,并从该公司获得了咨询费,他也是Embryotools的员工、股东和公司官员。A.M.是imagine Life Sciences的股东和公司官员,并持有TMRW Life Sciences的股份。M.A.是imagine Life Sciences的股票期权持有人,并获得公司的咨询费和差旅支持;她还获得了TMRW生命科学公司的咨询费。G.S.是imagine Life Sciences的员工和股票期权持有人,并从IVF 2.0获得咨询费。C.M.是imagine Life Sciences的雇员和股票期权持有人。E.H.-M。是想象生命科学公司的员工和股票期权持有人。R.V.-M。他是imagine Life Sciences的员工和股票期权持有人,并获得了IVF 2.0的咨询费。V.M.是想象生命科学公司的雇员兼股票期权持有人。E.M.是Embryotools的雇员。avva没有利益冲突需要申报。V.O.-H。他是imagine Life Sciences的员工和股票期权持有人,并获得了IVF 2.0的咨询费。F.A.-G。是想象生命科学公司的员工和股票期权持有人。A.A.L.是想象生命科学公司的员工和股票期权持有人。硕士 是Embryotools的雇员。Q.M.-A。是Embryotools的雇员。J.G.E.F.是想象生命科学公司的雇员和股票期权持有人。L.M.C.O.没有利益冲突需要申报。C.P.B.是想象生命科学公司的雇员和股票期权持有人。D.J.S.-G。没有利益冲突要申报。J.C.是imagine Life Sciences的员工、股东、股票期权持有人和公司官员,并持有IVF 2.0、Althea Science、TMRW Life Sciences、Kindbody和Reproductive Healthcare的股份。此外,A.C.-B。, G.M.-R。, a.f.f., a.m., a.Á.l。和J.C.宣布为美国专利12,349,940 B2的发明人,该专利保护自动卵母细胞剥离。A.C.-B。, G.M.-R。, a.f. - s.f., c.m., r.v.m.。, V.O.-H。, E.H.-M。, v.m., a.m.和J.C.宣布美国专利12,245,793 B2保护试管婴儿实验室的机器人处理系统的发明人。A.C.-B。, G.M.-R。, a.f. - s.f., c.m., g.s., v.m., j.c.和A.M.在美国专利12,178,475 B1上宣布为发明人,保护自动精子制备。A.C.-B。, G.M.-R。, a.m.和J.C.在美国专利12,180,441 B1上宣布为发明人,保护实验室工作流程自动化。A.C.-B。, G.M.-R。上午,下午,下午,下午,下午。, V.O.-H。, N.C.-B。, A.A.L.J.C.和J.C.宣布为美国专利12,268,418 B2的发明人,该专利保护自动卵母细胞制备。A.C.-B。, G.M.-R。, R.V.-M。, V.O.-H。, N.C.-B。, E.H.-M。, a.m., j.c.和A.F.-S.F.宣布为保护自动ICSI的美国专利12,310,625 B2的发明者。A.C.-B。, G.M.-R。, a.f.s., c.m., v.o.h。,和A.M.宣布为美国专利12,253,516 B2,保护试管婴儿自动化光学系统。A.C.-B。, G.M.-R。,上午,j.c., a.f.f., c.m., r.v.m.。, V.O.-H。, g.s., n.c.-b。和J.G.E.F.宣布拥有保护自动玻璃化的美国专利12,226,125 B2。A.C.-B。, G.M.-R。, c.m., r.v.m。, V.O.-H。, N.C.-B。, v.m.和J.C.宣布为美国专利US 12,478,405 B2的发明人,该专利保护自动碟式精子制备。A.C.-B。, G.M.-R。, c.m., n.c.-b。m.a., m.a.和J.C.宣布为一项正在申请中的专利申请的发明人,该专利申请保护自动餐具制备技术。A.C.-B。,
{"title":"Automated oocyte retrieval, denudation, sperm preparation, and ICSI in the IVF laboratory: a proof-of-concept study and report of the first live births.","authors":"A Chavez-Badiola,G Mendizabal-Ruiz,A Flores-Saiffe Farías,N Costa-Borges,A Murray,M Alikani,G Silvestri,C Millan,E Hernández-Morales,R Valencia-Murillo,V Medina,E Mestres,A Valadez Aguilar,V Ocegueda-Hernández,F Acosta-Gómez,A Álvarez López,M Acacio,Q Matia-Algué,J G Espinoza Figueroa,L M Campos Olmedo,C P Barragan,D J Sánchez-González,J Cohen","doi":"10.1093/humrep/deaf240","DOIUrl":"https://doi.org/10.1093/humrep/deaf240","url":null,"abstract":"STUDY QUESTIONCan multiple automated systems sequentially perform Day 0 IVF procedures: (i) sperm preparation, (ii) cumulus-oocyte complex (COC) retrieval and oocyte denudation, and (iii) ICSI?SUMMARY ANSWERAutomated sequential Day 0 procedures achieved fertilization in 64.3% of injected oocytes and 42.2% usable blastocyst formation in 11 cases, resulting in five healthy live births from nine patients with positive pregnancy tests.WHAT IS KNOWN ALREADYThe Day 0 procedures-sperm preparation, oocyte handling (e.g. finding and denudation), and ICSI-rely on embryologist skill. Automation in IVF laboratories has the potential to improve reproducibility, yet its implementation remains limited. Fully automated pipetting workflows replicating embryologist activities have not yet been achieved, though partial automation of key steps such as dish preparation and ICSI has been reported.STUDY DESIGN, SIZE, DURATIONProof-of-concept pilot study with prospective allocation of sibling oocytes to automated or manual protocols. Here, we report on Day 0 automation in 11 cases using two or three automated systems (nicknamed 'pearls') in sequence. Single vitrified/warmed blastocyst transfers occurred between April and October 2024. This work was part of a larger research programme evaluating automation across multiple IVF laboratory procedures from gamete handling through blastocyst transfer and specifically demonstrates sequential automation across multiple Day 0 procedures within a single workflow.PARTICIPANTS/MATERIALS, SETTING, METHODSEleven consenting patients (three autologous, eight donor egg cycles) underwent IVF/ICSI following minimal or mild stimulation. The gametes were processed using either automated or manual protocols. The automated systems-Pearl 1 (sperm preparation), Pearl 2 (COC retrieval and oocyte denudation), and Pearl 3 (sperm selection, laser immobilization, and piezo-ICSI)-were used in various combinations. Multiple AIs were developed and deployed across these systems. This IRB-approved study was conducted at Hope IVF, Guadalajara, México.MAIN RESULTS AND THE ROLE OF CHANCEThe automated systems achieved 64.3% fertilization (45/70) and 42.2% usable blastocyst formation per zygote (19/45), compared to 81% (47/58) and 59.6% (28/47) with manual procedures. Transfers from the automated arm resulted in five live births, three biochemical pregnancies, and one early loss at 7 weeks. The live birth rate per transfer of a single warmed blastocyst in the automated arm was 5/12 (41.7%).LIMITATIONS, REASONS FOR CAUTIONThe small sample size prevented statistical comparison between automated and manual procedures. Some steps required operator support via direct intervention or digital control. Autonomy (defined as automated execution without human intervention) was achieved only in sperm preparation and selected ICSI tasks. A larger study using an updated system is underway.WIDER IMPLICATIONS OF THE FINDINGSThis study demonstrates the feasibility of automati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"11 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835988","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
Obstetrical, perinatal, and children's health outcomes following fresh embryo transfer after extended embryo culture. 延长胚胎培养后新鲜胚胎移植后的产科、围产期和儿童健康结果
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-26 DOI: 10.1093/humrep/deaf245
Patricia Fauque,Jonathan Cottenet,Julie Firmin,Khaled Pocate-Cheriet,Lucile Ferreux,Ahmed Chargui,Solène Tapia,Chloé Maignien,Mathilde Bourdon,Pietro Santulli,Catherine Patrat,Catherine Quantin
STUDY QUESTIONDoes extended embryo culture (EEC) associate with an increased risk of obstetrical, perinatal, or children's health complications?SUMMARY ANSWERAfter thorough adjustment, EEC was not associated with widespread increased risks, although a moderate excess risk persisted for a few specific outcomes, notably cardiac anomalies, whereas reduced risks were observed for gestational diabetes, small birthweight, and musculoskeletal-limb anomalies.WHAT IS KNOWN ALREADYEEC is increasingly used in IVF cycles. While blastocyst transfer (day-5/6) often improves birth rates, concerns remain about its impact on maternal and child health.STUDY DESIGN, SIZE, DURATIONIn this nationwide longitudinal cohort study, all live-born singletons conceived through IVF-with or without sperm microinjection-and following fresh embryo transfer between 2014 and 2019 in France were included and followed for up to 8 years.PARTICIPANTS/MATERIALS, SETTING, METHODSData were obtained from the French National Health System and the National Biomedicine Agency registries. A comparative study was conducted between singletons conceived at either day-2/3 (cleavage-stage embryos group) or day-5/6 (EEC group). Data from both registries were cross-linked to identify obstetrical, perinatal, and health outcomes, including major congenital malformations, hospitalizations, and surgical interventions. Multivariable logistic and survival models were used to adjust for maternal, paternal, and treatment-related factors.MAIN RESULTS AND THE ROLE OF CHANCEA total of 41 315 singletons were included (25 816 and 15 499 from day-2/3 and day-5/6 groups, respectively). Most outcomes were similar between groups, notably the incidence of global major congenital malformations. However, EEC was associated with increased risks of placenta praevia (aOR, 1.16; 95% CI, 1.02-1.30), admission in neonatal intensive care unit (aOR, 1.16; 95% CI, 1.05-1.29), and cardiac anomalies at age 3 years (aHR, 1.78; 95% CI, 1.21-2.60). Conversely, the risk of gestational diabetes (aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041) and small birthweight (aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039) was lower, as was the risk of musculoskeletal-limb anomalies (aHR, 0.63; 95% CI, 0.42-0.97)-a finding that persisted up to age 7. Other health outcomes were largely comparable.LIMITATIONS, REASONS FOR CAUTIONOne limitation of this study is that the data refer to live-born singletons, with stillbirths and medical terminations excluded from the analyses. Despite extensive adjustments, residual confounding cannot be excluded. Findings for specific pathologies/malformations should be interpreted with caution because the number of cases was small in some sub-groups.WIDER IMPLICATIONS OF THE FINDINGSIn this large and unique study, after adjusting for multiple maternal, paternal, and cycle-related variables, our findings provide some reassurance regarding the safety of prolonged in vitro embryo culture. A moderate risk remained for a few maternal
研究问题:延长胚胎培养(EEC)是否与产科、围产期或儿童健康并发症的风险增加有关?经过彻底调整后,EEC与广泛增加的风险无关,尽管在一些特定的结果中,特别是心脏异常,存在中度过度风险,而在妊娠糖尿病、出生体重过轻和肌肉骨骼-肢体异常中,观察到风险降低。已经知道的是,试管婴儿周期越来越多地使用ec。虽然囊胚移植(第5/6天)通常可以提高出生率,但人们仍然担心其对孕产妇和儿童健康的影响。研究设计、规模、持续时间在这项全国性的纵向队列研究中,纳入了2014年至2019年在法国通过体外受精(有或没有精子微注射)和新鲜胚胎移植受孕的所有活产单胎,并随访长达8年。参与者/材料、环境、方法数据来自法国国家卫生系统和国家生物医药管理局登记处。对2/3天(卵裂期胚胎组)和5/6天(EEC组)的单胎进行比较研究。来自两个登记处的数据被交叉链接,以确定产科、围产期和健康结果,包括主要先天性畸形、住院和手术干预。使用多变量逻辑模型和生存模型来调整母亲、父亲和治疗相关因素。主要结果及机会的作用共纳入41 315例单胎(第2/3天和第5/6天组分别为25 816例和15 499例)。大多数结果在两组之间相似,特别是全球重大先天性畸形的发生率。然而,EEC与前置胎盘(aOR, 1.16; 95% CI, 1.02-1.30)、新生儿重症监护病房入院(aOR, 1.16; 95% CI, 1.05-1.29)和3岁时心脏异常(aHR, 1.78; 95% CI, 1.21-2.60)的风险增加相关。相反,妊娠期糖尿病(aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041)和出生体重过轻(aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039)的风险较低,肌肉骨骼肢体异常(aHR, 0.63; 95% CI, 0.42-0.97)的风险也较低,这一发现一直持续到7岁。其他健康结果在很大程度上具有可比性。局限性,注意原因本研究的一个局限性是,数据是指活产的单胎,死产和医学终止排除在分析之外。尽管进行了广泛的调整,仍不能排除残留的混杂因素。特殊病理/畸形的发现应谨慎解释,因为在某些亚组中病例数很少。在这项大型而独特的研究中,在调整了多个母体、父亲和周期相关变量后,我们的研究结果为长期体外胚胎培养的安全性提供了一些保证。eec后的一些产妇和儿童健康状况仍有中等风险,值得进一步调查,而与短胚胎培养相比,风险明显较低,特别是对于肌肉骨骼和肢体异常。研究经费/竞争利益(S)本工作由第戎大学医院AOI支持。作者没有需要披露的竞争利益。试验注册号/ a。
{"title":"Obstetrical, perinatal, and children's health outcomes following fresh embryo transfer after extended embryo culture.","authors":"Patricia Fauque,Jonathan Cottenet,Julie Firmin,Khaled Pocate-Cheriet,Lucile Ferreux,Ahmed Chargui,Solène Tapia,Chloé Maignien,Mathilde Bourdon,Pietro Santulli,Catherine Patrat,Catherine Quantin","doi":"10.1093/humrep/deaf245","DOIUrl":"https://doi.org/10.1093/humrep/deaf245","url":null,"abstract":"STUDY QUESTIONDoes extended embryo culture (EEC) associate with an increased risk of obstetrical, perinatal, or children's health complications?SUMMARY ANSWERAfter thorough adjustment, EEC was not associated with widespread increased risks, although a moderate excess risk persisted for a few specific outcomes, notably cardiac anomalies, whereas reduced risks were observed for gestational diabetes, small birthweight, and musculoskeletal-limb anomalies.WHAT IS KNOWN ALREADYEEC is increasingly used in IVF cycles. While blastocyst transfer (day-5/6) often improves birth rates, concerns remain about its impact on maternal and child health.STUDY DESIGN, SIZE, DURATIONIn this nationwide longitudinal cohort study, all live-born singletons conceived through IVF-with or without sperm microinjection-and following fresh embryo transfer between 2014 and 2019 in France were included and followed for up to 8 years.PARTICIPANTS/MATERIALS, SETTING, METHODSData were obtained from the French National Health System and the National Biomedicine Agency registries. A comparative study was conducted between singletons conceived at either day-2/3 (cleavage-stage embryos group) or day-5/6 (EEC group). Data from both registries were cross-linked to identify obstetrical, perinatal, and health outcomes, including major congenital malformations, hospitalizations, and surgical interventions. Multivariable logistic and survival models were used to adjust for maternal, paternal, and treatment-related factors.MAIN RESULTS AND THE ROLE OF CHANCEA total of 41 315 singletons were included (25 816 and 15 499 from day-2/3 and day-5/6 groups, respectively). Most outcomes were similar between groups, notably the incidence of global major congenital malformations. However, EEC was associated with increased risks of placenta praevia (aOR, 1.16; 95% CI, 1.02-1.30), admission in neonatal intensive care unit (aOR, 1.16; 95% CI, 1.05-1.29), and cardiac anomalies at age 3 years (aHR, 1.78; 95% CI, 1.21-2.60). Conversely, the risk of gestational diabetes (aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041) and small birthweight (aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039) was lower, as was the risk of musculoskeletal-limb anomalies (aHR, 0.63; 95% CI, 0.42-0.97)-a finding that persisted up to age 7. Other health outcomes were largely comparable.LIMITATIONS, REASONS FOR CAUTIONOne limitation of this study is that the data refer to live-born singletons, with stillbirths and medical terminations excluded from the analyses. Despite extensive adjustments, residual confounding cannot be excluded. Findings for specific pathologies/malformations should be interpreted with caution because the number of cases was small in some sub-groups.WIDER IMPLICATIONS OF THE FINDINGSIn this large and unique study, after adjusting for multiple maternal, paternal, and cycle-related variables, our findings provide some reassurance regarding the safety of prolonged in vitro embryo culture. A moderate risk remained for a few maternal ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835987","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
Family planning of infertile couples: a systematic review of intentions regarding parenthood and return to ART. 不孕夫妇的计划生育:关于生育意图和重返抗逆转录病毒疗法的系统回顾。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-22 DOI: 10.1093/humrep/deaf239
Letizia Li Piani,Giovanna Esposito,Marco Reschini,Jacques Donnez,Fabio Parazzini,Edgardo Somigliana
STUDY QUESTIONWhat motivations and barriers influence family planning decisions among infertile individuals?SUMMARY ANSWERIn studying the family planning of infertile couples, this review found that a significant gap persists between desired and achieved family size.WHAT IS KNOWN ALREADYWhile ART has traditionally focused on live birth rate (LBR) as a primary success parameter, growing attention has been paid to whether treatments help couples achieve their desired family size. Evidence suggests that many infertile couples do not return to ART for subsequent children, despite having cryopreserved embryos available.STUDY DESIGN, SIZE, DURATIONThis review was conducted as a systematic review following PRISMA guidelines. A comprehensive search strategy was developed and implemented across PubMed and Embase databases, covering studies published in English up to May 2025. The search combined free text terms and MeSH/Emtree terms related to 'infertility' and 'family planning'.PARTICIPANTS/MATERIALS, SETTING, METHODSWe included observational studies reporting outcomes related to family size, return to ART, or intentions for subsequent children. Two reviewers independently performed screening, data extraction, and quality assessment using the Newcastle-Ottawa Scale.MAIN RESULTS AND THE ROLE OF CHANCEOf 2495 screened records, 9 studies were included. Across contexts, infertile couples consistently reported smaller family sizes compared to fertile ones. Return rates to ART for a second child ranged from 25 to 50%, even among those with cryopreserved embryos. Factors associated with return included younger age, availability of embryos, and previous treatment characteristics. However, emotional, financial, and social burdens often discouraged further ART use. Success rates for second ART pregnancies varied, with cumulative LBRs between 38 and 88%, depending on treatment strategy and prior history.LIMITATIONS, REASONS FOR CAUTIONScarcity of evidence and high heterogeneity across studies, including differences in design, populations, outcomes, and type of ART, may have limited comparability of the studies.WIDER IMPLICATIONS OF THE FINDINGSThe low return rate to ART highlights unmet needs in post-treatment support and counselling. Future research should explore the psychosocial, economic, and systemic barriers that prevent couples from pursuing their reproductive goals, enabling more patient-centred care in reproductive medicine.STUDY FUNDING/COMPETING INTEREST(S)Open access funding was provided by Università degli Studi di Milano within the CRUI-CARE Agreement. This study was in part supported by the Italian Ministry of Health-Current Research IRCCS. E.S. reports receiving grants from Ferring and honoraria for lectures from Merck-Serono, IBSA, and Gedeon-Richter. J.D. has received consulting fees from ObsEva, Gedeon Richter, and Theramex and was a member of the scientific advisory board of ObsEva and Preglem until 2023. L.L.P. reports participation in a traini
研究问题:什么动机和障碍影响不孕个体的计划生育决策?在研究不孕夫妇的计划生育时,这篇综述发现在期望的和实现的家庭规模之间存在着显著的差距。虽然传统上ART关注的是活产率(LBR)作为主要的成功参数,但越来越多的人开始关注治疗是否能帮助夫妇达到理想的家庭规模。有证据表明,尽管有冷冻胚胎,许多不孕夫妇并没有为他们的孩子返回抗逆转录病毒治疗。研究设计、规模、持续时间本综述按照PRISMA指南作为系统综述进行。在PubMed和Embase数据库中开发并实施了一个全面的搜索策略,涵盖了截至2025年5月以英语发表的研究。该搜索结合了与“不孕”和“计划生育”相关的自由文本术语和MeSH/Emtree术语。参与者/材料、环境、方法我们纳入了观察性研究,这些研究报告了与家庭规模、重新接受抗逆转录病毒治疗或后续儿童意向相关的结果。两名审稿人使用纽卡斯尔-渥太华量表独立进行筛选、数据提取和质量评估。主要结果及机会的作用在2495份筛选记录中,纳入9项研究。在不同的背景下,不孕夫妇的家庭规模总是比有生育能力的夫妇小。即使是那些冷冻保存胚胎的人,二胎接受ART治疗的成功率也在25%到50%之间。与复发相关的因素包括年龄较小,胚胎的可用性和以前的治疗特征。然而,情感、经济和社会负担往往阻碍进一步使用抗逆转录病毒治疗。第二次ART妊娠的成功率各不相同,累积lbr在38%至88%之间,取决于治疗策略和既往病史。局限性、谨慎的原因证据的缺乏和研究之间的高度异质性,包括设计、人群、结果和ART类型的差异,可能限制了研究的可比性。研究结果的更广泛意义抗逆转录病毒治疗的低回复率突出了治疗后支持和咨询方面的需求未得到满足。未来的研究应该探索阻止夫妇追求生育目标的社会心理、经济和系统障碍,在生殖医学中实现更多以患者为中心的护理。研究资金/竞争利益(S)开放获取资金由米兰大学根据CRUI-CARE协议提供。这项研究得到了意大利卫生部当前研究中心的部分支持。E.S.报告从费林获得资助,并从默克-雪兰诺、IBSA和Gedeon-Richter获得讲学酬金。J.D.曾获得ObsEva, Gedeon Richter和Theramex的咨询费,并担任ObsEva和Preglem的科学顾问委员会成员,直到2023年。L.L.P.报告说,她参加了Gedeon Richter主办的培训课程,在此期间,作为培训课程的一部分,她获得了这篇论文的医学写作协助。其余作者声明没有竞争利益。登记NUMBERn /。
{"title":"Family planning of infertile couples: a systematic review of intentions regarding parenthood and return to ART.","authors":"Letizia Li Piani,Giovanna Esposito,Marco Reschini,Jacques Donnez,Fabio Parazzini,Edgardo Somigliana","doi":"10.1093/humrep/deaf239","DOIUrl":"https://doi.org/10.1093/humrep/deaf239","url":null,"abstract":"STUDY QUESTIONWhat motivations and barriers influence family planning decisions among infertile individuals?SUMMARY ANSWERIn studying the family planning of infertile couples, this review found that a significant gap persists between desired and achieved family size.WHAT IS KNOWN ALREADYWhile ART has traditionally focused on live birth rate (LBR) as a primary success parameter, growing attention has been paid to whether treatments help couples achieve their desired family size. Evidence suggests that many infertile couples do not return to ART for subsequent children, despite having cryopreserved embryos available.STUDY DESIGN, SIZE, DURATIONThis review was conducted as a systematic review following PRISMA guidelines. A comprehensive search strategy was developed and implemented across PubMed and Embase databases, covering studies published in English up to May 2025. The search combined free text terms and MeSH/Emtree terms related to 'infertility' and 'family planning'.PARTICIPANTS/MATERIALS, SETTING, METHODSWe included observational studies reporting outcomes related to family size, return to ART, or intentions for subsequent children. Two reviewers independently performed screening, data extraction, and quality assessment using the Newcastle-Ottawa Scale.MAIN RESULTS AND THE ROLE OF CHANCEOf 2495 screened records, 9 studies were included. Across contexts, infertile couples consistently reported smaller family sizes compared to fertile ones. Return rates to ART for a second child ranged from 25 to 50%, even among those with cryopreserved embryos. Factors associated with return included younger age, availability of embryos, and previous treatment characteristics. However, emotional, financial, and social burdens often discouraged further ART use. Success rates for second ART pregnancies varied, with cumulative LBRs between 38 and 88%, depending on treatment strategy and prior history.LIMITATIONS, REASONS FOR CAUTIONScarcity of evidence and high heterogeneity across studies, including differences in design, populations, outcomes, and type of ART, may have limited comparability of the studies.WIDER IMPLICATIONS OF THE FINDINGSThe low return rate to ART highlights unmet needs in post-treatment support and counselling. Future research should explore the psychosocial, economic, and systemic barriers that prevent couples from pursuing their reproductive goals, enabling more patient-centred care in reproductive medicine.STUDY FUNDING/COMPETING INTEREST(S)Open access funding was provided by Università degli Studi di Milano within the CRUI-CARE Agreement. This study was in part supported by the Italian Ministry of Health-Current Research IRCCS. E.S. reports receiving grants from Ferring and honoraria for lectures from Merck-Serono, IBSA, and Gedeon-Richter. J.D. has received consulting fees from ObsEva, Gedeon Richter, and Theramex and was a member of the scientific advisory board of ObsEva and Preglem until 2023. L.L.P. reports participation in a traini","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"29 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807917","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
A homozygous variant in HFM1 causes preimplantation embryo developmental arrest by disrupting zygotic genome activation. HFM1的纯合子变异通过破坏合子基因组激活导致着床前胚胎发育停滞。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-22 DOI: 10.1093/humrep/deaf238
Y-W Zhang,X-G Zhang,P-Y Li,T-G Meng,F-F Xu,M-Y Liu,H-J Zhu,L-N Chen,L Zeng,J Li,Z Yang,S-M Luo,Q-Y Sun,J Chen,S Li,X-H Ou
STUDY QUESTIONDoes a homozygous HFM1 mutation cause human embryonic developmental arrest by disrupting zygotic genome activation?SUMMARY ANSWERA pathogenic homozygous HFM1 mutation causes aberrant mRNA splicing and produces a protein that fails to localize to the nucleus, leading to widespread transcriptional dysregulation, failure of zygotic genome activation, and consequent embryonic arrest.WHAT IS KNOWN ALREADYHFM1 (Helicase 1) is a germ cell-specific gene that plays a pivotal role in meiotic recombination and DNA damage repair, and its mutations are linked to premature ovarian insufficiency. While HFM1 knockout mice exhibit fertility defects, the mechanism by which HFM1 mutations cause preimplantation embryonic arrest in humans, particularly its role in zygotic genome activation, remains unclear.STUDY DESIGN, SIZE, DURATIONThis was a case-based experimental study conducted from June to November 2024, involving a single infertile patient carrying a homozygous HFM1 mutation and experiencing recurrent embryonic arrest. Analyses included molecular characterization of patient embryos and functional validation in a mouse model.PARTICIPANTS/MATERIALS, SETTING, METHODSThe patient was recruited from the Reproductive Medicine Centre of the Affiliated Guangdong Second Provincial General Hospital of Jinan University. Whole-exome sequencing identified a homozygous HFM1 mutation. Minigene assays, RNA-seq, immunofluorescence, and confocal imaging were used to characterize the mutation's impact on splicing, protein localization, and transcriptomic and epigenetic states. Functional rescue experiments were performed in mouse embryos.MAIN RESULTS AND THE ROLE OF CHANCEFunctional analysis confirmed that the HFM1 mutation disrupts normal mRNA splicing, leading to the production of a protein variant that is excluded from the nucleus. Transcriptomic and epigenetic profiling of arrested human embryos linked the abnormal localization of this protein to a failure in zygotic genome activation and aberrant retention of H3K27me3. The essential role of HFM1 was further verified in a mouse model, where embryonic defects induced by HFM1 knockdown were specifically rescued by wild-type HFM1 mRNA, but not by the mutant version.LIMITATIONS, REASONS FOR CAUTIONThe findings are based on a single clinical case and a limited number of embryos. Further studies with larger cohort studies are needed to validate the prevalence and pathogenicity of such mutations. Further mechanistic studies are also required to fully elucidate how HFM1 regulates gene expression and epigenetic remodeling.WIDER IMPLICATIONS OF THE FINDINGSThis study establishes that nuclear localization of HFM1 may be essential for ZGA and early embryogenesis in humans. It provides a mechanistic link between noncoding HFM1 variants, transcriptional dysregulation, epigenetic dysregulation, and embryonic arrest, expanding the genetic understanding of female infertility and informing future diagnostic approaches.STUDY FUND
研究问题纯合子HFM1突变是否通过破坏合子基因组激活导致人类胚胎发育停滞?致病性纯合子HFM1突变会导致mRNA剪接异常,并产生一种无法定位到细胞核的蛋白质,从而导致广泛的转录失调,合子基因组激活失败,进而导致胚胎停滞。hfm1(解旋酶1)是一种生殖细胞特异性基因,在减数分裂重组和DNA损伤修复中起关键作用,其突变与卵巢功能不全有关。虽然HFM1基因敲除小鼠表现出生育缺陷,但HFM1突变导致人类着床前胚胎停滞的机制,特别是其在合子基因组激活中的作用,仍不清楚。研究设计、规模、持续时间这是一项基于病例的实验研究,于2024年6月至11月进行,涉及一名携带纯合子HFM1突变并经历反复胚胎骤停的不育患者。分析包括患者胚胎的分子特征和小鼠模型的功能验证。参与者/材料、环境、方法患者从暨南大学附属广东省第二总医院生殖医学中心招募。全外显子组测序鉴定出纯合子HFM1突变。miniigene分析、RNA-seq、免疫荧光和共聚焦成像被用来表征突变对剪接、蛋白质定位、转录组和表观遗传状态的影响。在小鼠胚胎中进行功能恢复实验。主要结果和chance - functional分析证实,HFM1突变破坏正常的mRNA剪接,导致一种被排除在细胞核外的蛋白质变体的产生。捕获人类胚胎的转录组学和表观遗传学分析将该蛋白的异常定位与合子基因组激活失败和H3K27me3的异常保留联系起来。在小鼠模型中,HFM1的重要作用得到了进一步的验证,在小鼠模型中,由HFM1敲低引起的胚胎缺陷被野生型的HFM1 mRNA特异性地挽救,而不是突变型的HFM1 mRNA。局限性,谨慎的原因该发现是基于一个临床病例和有限数量的胚胎。需要进一步的大规模队列研究来验证这些突变的患病率和致病性。还需要进一步的机制研究来充分阐明HFM1如何调节基因表达和表观遗传重塑。本研究证实HFM1的核定位可能对ZGA和人类早期胚胎发生至关重要。它提供了非编码HFM1变异、转录失调、表观遗传失调和胚胎停止之间的机制联系,扩大了对女性不孕症的遗传理解,并为未来的诊断方法提供了信息。研究经费/竞争利益(S)本研究由国家重点研发计划项目(2022YFC2702200)、国家自然科学基金项目(82271728)和广东省重点基础与应用研究项目(2023B1515120027)资助。所有作者都没有任何利益冲突。试验注册号/a。
{"title":"A homozygous variant in HFM1 causes preimplantation embryo developmental arrest by disrupting zygotic genome activation.","authors":"Y-W Zhang,X-G Zhang,P-Y Li,T-G Meng,F-F Xu,M-Y Liu,H-J Zhu,L-N Chen,L Zeng,J Li,Z Yang,S-M Luo,Q-Y Sun,J Chen,S Li,X-H Ou","doi":"10.1093/humrep/deaf238","DOIUrl":"https://doi.org/10.1093/humrep/deaf238","url":null,"abstract":"STUDY QUESTIONDoes a homozygous HFM1 mutation cause human embryonic developmental arrest by disrupting zygotic genome activation?SUMMARY ANSWERA pathogenic homozygous HFM1 mutation causes aberrant mRNA splicing and produces a protein that fails to localize to the nucleus, leading to widespread transcriptional dysregulation, failure of zygotic genome activation, and consequent embryonic arrest.WHAT IS KNOWN ALREADYHFM1 (Helicase 1) is a germ cell-specific gene that plays a pivotal role in meiotic recombination and DNA damage repair, and its mutations are linked to premature ovarian insufficiency. While HFM1 knockout mice exhibit fertility defects, the mechanism by which HFM1 mutations cause preimplantation embryonic arrest in humans, particularly its role in zygotic genome activation, remains unclear.STUDY DESIGN, SIZE, DURATIONThis was a case-based experimental study conducted from June to November 2024, involving a single infertile patient carrying a homozygous HFM1 mutation and experiencing recurrent embryonic arrest. Analyses included molecular characterization of patient embryos and functional validation in a mouse model.PARTICIPANTS/MATERIALS, SETTING, METHODSThe patient was recruited from the Reproductive Medicine Centre of the Affiliated Guangdong Second Provincial General Hospital of Jinan University. Whole-exome sequencing identified a homozygous HFM1 mutation. Minigene assays, RNA-seq, immunofluorescence, and confocal imaging were used to characterize the mutation's impact on splicing, protein localization, and transcriptomic and epigenetic states. Functional rescue experiments were performed in mouse embryos.MAIN RESULTS AND THE ROLE OF CHANCEFunctional analysis confirmed that the HFM1 mutation disrupts normal mRNA splicing, leading to the production of a protein variant that is excluded from the nucleus. Transcriptomic and epigenetic profiling of arrested human embryos linked the abnormal localization of this protein to a failure in zygotic genome activation and aberrant retention of H3K27me3. The essential role of HFM1 was further verified in a mouse model, where embryonic defects induced by HFM1 knockdown were specifically rescued by wild-type HFM1 mRNA, but not by the mutant version.LIMITATIONS, REASONS FOR CAUTIONThe findings are based on a single clinical case and a limited number of embryos. Further studies with larger cohort studies are needed to validate the prevalence and pathogenicity of such mutations. Further mechanistic studies are also required to fully elucidate how HFM1 regulates gene expression and epigenetic remodeling.WIDER IMPLICATIONS OF THE FINDINGSThis study establishes that nuclear localization of HFM1 may be essential for ZGA and early embryogenesis in humans. It provides a mechanistic link between noncoding HFM1 variants, transcriptional dysregulation, epigenetic dysregulation, and embryonic arrest, expanding the genetic understanding of female infertility and informing future diagnostic approaches.STUDY FUND","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"11 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800994","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
Testing the efficacy of a self-guided psychotherapy intervention for infertility-related distress: a randomized controlled trial. 测试自我引导的心理治疗干预不孕相关困扰的效果:一项随机对照试验。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-16 DOI: 10.1093/humrep/deaf237
M M L Poulter,T D Wahl,M J Kiviharju,T S Campbell,J L Gordon
STUDY QUESTIONIs the online 7-week self-help Coping with Infertility (CWI) program more effective than treatment as usual (TAU) at improving mental health for individuals assigned female at birth (AFAB) who are experiencing infertility?SUMMARY ANSWERAFAB individuals who participated in the CWI program experienced improvements in quality of life, distress, depression, and anxiety relative to TAU; these effects were large among those with poorer quality of life or greater symptoms of depressed mood and anxiety at baseline.WHAT IS KNOWN ALREADYExisting psychological interventions are associated with small improvements in mental health relative to TAU for individuals experiencing infertility. A newly developed, brief tailored intervention has been well received, yet has not been rigorously tested in a randomized controlled trial (RCT).STUDY DESIGN, SIZE, DURATIONA parallel RCT was conducted between January and November 2024 (start of recruitment and end of data collection, respectively). AFAB adults experiencing infertility were randomly assigned to either the CWI program or a waitlist/TAU control group using a predetermined stratified block randomization scheme. The sample (n = 173) was powered to detect a medium effect on continuous outcomes.PARTICIPANTS/MATERIALS, SETTING, METHODSThere was an approximately equal number of participants assigned to the CWI program (n = 87) as to the waitlist/TAU control group (n = 86). Participants assigned to the CWI program were emailed one 10-minute video module every week for 7 weeks or received access to the videos on a mobile app. Participants in the waitlist/TAU control group continued with their everyday life until the conclusion of the study. Psychological outcomes were assessed at baseline, post-treatment, and biweekly for 16 weeks post-treatment. Fourteen participants were either excluded from analyses or lost to follow-up, leaving 160 (CWI program n = 77, waitlist/TAU control group n = 83) for intent-to-treat analyses.MAIN RESULTS AND THE ROLE OF CHANCEParticipants who engaged with the CWI program reported higher fertility-related quality of life throughout the follow-up period relative to those assigned to the waitlist/TAU control group, M (SE) = 63.2 (0.5) versus 54.5 (0.5), Cohen's d = .53, P < .001; as well as lower infertility-related distress, M (SE) = 21.6 (0.2) versus 23.9 (0.2), d = .35, P < .001; depressed mood, M (SE) = 5.3 (0.2) versus 7.7 (0.2), d = .56, P < .001; and anxiety, M (SE) = 5.1 (0.2) versus 7.7 (0.2), d = .66, P < .001. Treatment effects were pronounced for participants with poorer quality of life or clinically significant symptoms of depressed mood and anxiety at baseline, with large effect sizes ranging between Cohen's d = 0.91-1.10 in these subgroups. Treatment effects on relationship quality, mood and anxiety disorders, and pregnancy rates were not statistically significant (P > .05).LIMITATIONS, REASONS FOR CAUTIONThe lack of an active control condition, use of self-report d
研究问题:在线7周自助应对不孕症(CWI)计划比常规治疗(TAU)更有效地改善患有不孕症的女性出生(AFAB)个体的心理健康吗?与TAU相比,参加CWI项目的afab个体在生活质量、痛苦、抑郁和焦虑方面有所改善;这些影响在那些生活质量较差或基线时抑郁情绪和焦虑症状较严重的人群中更为明显。现有的心理干预措施与患有不孕症的个体相对于TAU的心理健康的小幅改善有关。一种新开发的、简短的量身定制的干预措施得到了广泛的认可,但尚未在随机对照试验(RCT)中进行严格的测试。研究设计、规模、持续时间一项平行随机对照试验于2024年1月至11月(分别为招募开始和数据收集结束)进行。使用预先确定的分层块随机化方案,将患有不孕症的AFAB成人随机分配到CWI计划或等待名单/TAU对照组。样本(n = 173)对连续结果有中等影响。参与者/材料,设置,方法分配给CWI计划(n = 87)的参与者人数与分配给等待名单/TAU对照组(n = 86)的参与者人数大致相同。被分配到CWI项目的参与者每周通过电子邮件发送一个10分钟的视频模块,持续7周,或者在移动应用程序上获得视频的访问。等候名单/TAU对照组的参与者继续他们的日常生活,直到研究结束。心理结果在基线、治疗后和治疗后16周每两周评估一次。14名参与者被排除在分析之外或未能随访,留下160名(CWI计划n = 77,等待名单/TAU对照组n = 83)进行意向治疗分析。主要结果和机会的作用参与CWI计划的参与者在整个随访期间的生育相关生活质量相对于分配给等待名单/TAU对照组的参与者更高,M (SE) = 63.2(0.5)对54.5 (0.5),Cohen's d = 0.53, P < .001;以及较低的不孕相关痛苦,M (SE) = 21.6(0.2)对23.9 (0.2),d = 0.35, P < 0.001;抑郁情绪,M (SE) = 5.3 (0.2) vs . 7.7 (0.2), d = 0.56, P < 0.001;M (SE) = 5.1(0.2)比7.7 (0.2),d = 0.66, P < 0.001。对于生活质量较差或在基线时有抑郁情绪和焦虑临床症状的参与者,治疗效果明显,这些亚组的效应量在Cohen's d = 0.91-1.10之间。治疗对关系质量、情绪和焦虑障碍、妊娠率的影响无统计学意义(P < 0.05)。局限性、谨慎原因缺乏主动对照条件、使用自我报告数据、异质性人群和有限的随访期限制了本研究可以得出的经验结论。研究结果的更广泛意义这些结果确立了CWI计划作为AFAB患者在不孕期间经历生活质量下降或增加痛苦、抑郁情绪和焦虑的有效短期治疗选择,解决了不孕治疗的重大空白。研究资金/竞争利益(S) CWI计划的发展和试点得到了萨斯喀彻温省健康研究基金会(SHRF)以患者为导向的领导者奖(#4577)的支持。目前的研究得到了加拿大卫生研究项目资助(#PJT186221)和SHRF研究联系资助(#6447)的支持。两家资助机构均未参与研究设计;数据的收集、管理、分析和解释;报告的撰写;或者提交报告发表的决定。作者对本文的内容负全部责任,文中所描述的观点和意见仅反映作者的观点和意见。J.L.G.还获得加拿大卫生研究所加拿大研究主席的薪金支持。所有作者声明他们在这个项目的写作中没有财务、个人或专业上的竞争利益。试验注册号:clinicaltrials .gov NCT06006936。试验注册日期为2023年8月17日。第一位患者入组日期2024年1月8日。
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引用次数: 0
Surrogates 20 years on: long-term psychological health, contact with surrogacy families, and thoughts and feelings about post-birth contact. 代孕20年:长期心理健康,与代孕家庭的接触,产后接触的想法和感受。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-12 DOI: 10.1093/humrep/deaf234
V Jadva,K Shaw,P Hall,S Ross,S Imrie
STUDY QUESTIONWhat were the psychological health outcomes for surrogates 20 years after the surrogacy pregnancy?SUMMARY ANSWERMost surrogates did not experience psychological problems 20 years after the pregnancy with many showing positive psychological wellbeing.WHAT IS KNOWN ALREADYStudies of surrogates from the global north have found that although some surrogates may experience psychological difficulties in the weeks following the birth of the child, this decreases over time, with most surrogates not experiencing psychological problems at 6 months, 1 year or 10 years following the birth.STUDY DESIGN, SIZE, DURATIONCross-sectional follow-up study of 21 surrogates who had conducted surrogacy ∼20 years previously (M = 20.33 years, SD = 3.31, range 13-26 years). Data are presented from phase 3 of the study. All participants were interviewed and 17 completed psychometric scales. Data were collected between December 2021 and September 2022.PARTICIPANTS/MATERIALS, SETTING, METHODSTwenty-one surrogates participated in the study. Ten surrogates (48%) had completed only gestational surrogacy arrangements, five (24%) had completed only traditional surrogacy arrangements, and six (29%) had completed both traditional and gestational surrogacy arrangements. All were domestic arrangements for heterosexual couples. Data were collected using semi-structured interviews and standardized psychometric questionnaires to assess experiences of surrogacy and psychological health of surrogates. Data on frequency of contact and relationship with the surrogacy family were also obtained.MAIN RESULTS AND THE ROLE OF CHANCESeventeen of the 21 surrogates completed the questionnaires assessing mental health and psychological wellbeing. None of the 17 surrogates who completed the assessments of psychological health showed signs of depression. Four surrogates scored above the cutoff of 5 on the General Health Questionnaire-30 indicating a 50% likelihood of having a psychiatric condition. Two of the four were in contact with a medical professional about their mental health. The mean score for self-esteem as measured by the Rosenberg Self-esteem Scale was within the normal range. The scores on the Scale of Positive and Negative Experience questionnaire showed moderately positive emotional balance for the majority of participants. Most surrogates scored within the normal range for satisfaction with life and flourishing. Thirteen (62%) surrogates had stayed in contact with the child with 11 describing their relationship as positive.LIMITATIONS, REASONS FOR CAUTIONSample size for this study was relatively small and some participants from previous phases were unable to be contacted or declined. Five surrogates had completed 11 surrogacy arrangements between them since Phase 2. Seven of these were gestational arrangements, however, whether donor gametes were used was not recorded.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to assess psychological health of surrogates 20
研究问题:代孕20年后,代孕母亲的心理健康状况如何?大多数代孕母亲在怀孕20年后没有出现心理问题,许多人表现出积极的心理健康。已知情况:对全球北方代孕母亲的研究发现,尽管一些代孕母亲在孩子出生后的几周内可能会出现心理问题,但随着时间的推移,这种情况会减少,大多数代孕母亲在孩子出生后的6个月、1年或10年都不会出现心理问题。研究设计、规模、持续时间对21名已有20年代孕经历的代孕母亲进行横断面随访研究(M = 20.33年,SD = 3.31,范围13-26年)。数据来自研究的第三阶段。所有参与者都接受了访谈,其中17人完成了心理测量量表。数据收集于2021年12月至2022年9月。受试者/材料、环境、方法21名替代受试者参与了本研究。10名代孕者(48%)只完成了妊娠代孕安排,5名(24%)只完成了传统代孕安排,6名(29%)同时完成了传统代孕和妊娠代孕安排。这些都是异性恋夫妇的家庭安排。采用半结构化访谈和标准化心理测量问卷收集数据,评估代孕经历和代孕母亲的心理健康状况。还获得了与代孕家庭接触频率和关系的数据。21名代孕母亲中有17名完成了心理健康和心理健康评估问卷。完成心理健康评估的17名代孕母亲中,没有人表现出抑郁的迹象。四名代理人在一般健康问卷中得分高于5分的分界点,即30分,表明有50%的可能性患有精神疾病。四人中有两人就他们的心理健康问题与医学专业人士进行了接触。Rosenberg自尊量表测量的自尊平均分在正常范围内。积极和消极体验量表的得分显示大多数参与者的情绪处于适度的积极平衡状态。大多数代孕妈妈对生活和事业的满意度都在正常范围内。13名(62%)代孕母亲与孩子保持联系,其中11人表示他们的关系是积极的。本研究的样本量相对较小,一些前阶段的参与者无法联系或被拒绝。自第二阶段以来,已有五名代孕母亲完成了11次代孕安排。然而,其中7例是妊娠安排,是否使用了供体配子没有记录。研究结果的更广泛意义这是第一个评估代孕母亲在孩子出生20年后心理健康状况的研究。研究结果表明,大多数代孕母亲在长期内没有出现心理问题。未来的研究应侧重于了解个人和环境因素在长期内对代孕母亲的消极和积极心理健康有何影响。研究经费/竞争利益(S)本研究由惠康信托基金(资助号208013/Z/17/Z)和剑桥大学返乡照顾者计划资助。作者无利益冲突需要申报。试验注册号/ a。
{"title":"Surrogates 20 years on: long-term psychological health, contact with surrogacy families, and thoughts and feelings about post-birth contact.","authors":"V Jadva,K Shaw,P Hall,S Ross,S Imrie","doi":"10.1093/humrep/deaf234","DOIUrl":"https://doi.org/10.1093/humrep/deaf234","url":null,"abstract":"STUDY QUESTIONWhat were the psychological health outcomes for surrogates 20 years after the surrogacy pregnancy?SUMMARY ANSWERMost surrogates did not experience psychological problems 20 years after the pregnancy with many showing positive psychological wellbeing.WHAT IS KNOWN ALREADYStudies of surrogates from the global north have found that although some surrogates may experience psychological difficulties in the weeks following the birth of the child, this decreases over time, with most surrogates not experiencing psychological problems at 6 months, 1 year or 10 years following the birth.STUDY DESIGN, SIZE, DURATIONCross-sectional follow-up study of 21 surrogates who had conducted surrogacy ∼20 years previously (M = 20.33 years, SD = 3.31, range 13-26 years). Data are presented from phase 3 of the study. All participants were interviewed and 17 completed psychometric scales. Data were collected between December 2021 and September 2022.PARTICIPANTS/MATERIALS, SETTING, METHODSTwenty-one surrogates participated in the study. Ten surrogates (48%) had completed only gestational surrogacy arrangements, five (24%) had completed only traditional surrogacy arrangements, and six (29%) had completed both traditional and gestational surrogacy arrangements. All were domestic arrangements for heterosexual couples. Data were collected using semi-structured interviews and standardized psychometric questionnaires to assess experiences of surrogacy and psychological health of surrogates. Data on frequency of contact and relationship with the surrogacy family were also obtained.MAIN RESULTS AND THE ROLE OF CHANCESeventeen of the 21 surrogates completed the questionnaires assessing mental health and psychological wellbeing. None of the 17 surrogates who completed the assessments of psychological health showed signs of depression. Four surrogates scored above the cutoff of 5 on the General Health Questionnaire-30 indicating a 50% likelihood of having a psychiatric condition. Two of the four were in contact with a medical professional about their mental health. The mean score for self-esteem as measured by the Rosenberg Self-esteem Scale was within the normal range. The scores on the Scale of Positive and Negative Experience questionnaire showed moderately positive emotional balance for the majority of participants. Most surrogates scored within the normal range for satisfaction with life and flourishing. Thirteen (62%) surrogates had stayed in contact with the child with 11 describing their relationship as positive.LIMITATIONS, REASONS FOR CAUTIONSample size for this study was relatively small and some participants from previous phases were unable to be contacted or declined. Five surrogates had completed 11 surrogacy arrangements between them since Phase 2. Seven of these were gestational arrangements, however, whether donor gametes were used was not recorded.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to assess psychological health of surrogates 20","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732757","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
Semen analysis as a biomarker of male aging: biological mechanisms, clinical implications, and public health perspectives. 精液分析作为男性衰老的生物标志物:生物学机制、临床意义和公共卫生观点。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-10 DOI: 10.1093/humrep/deaf232
Omar F Ammar,George Liperis,Zoya E Ali,Fabrizzio Horta,Attilio Anastasi,Dimitrios Rafail Kalaitzopoulos,Sara Ribeiro,Noemi Salmeri,R John Aitken,Pippa Sangster,Mónica Vazquez-Levin,Juan J Fraire-Zamora
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引用次数: 0
Culture media age does not affect IVF outcomes. 培养基年龄不影响体外受精结果。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-10 DOI: 10.1093/humrep/deaf236
Dean E Morbeck,Natalie Hesketh,Diana Bui
STUDY QUESTIONDoes the storage duration of a single-step embryo culture medium within its labelled 1-year shelf-life affect embryo development, pregnancy outcomes, or birthweight in IVF?SUMMARY ANSWERThe age of a single-step embryo culture medium with a 1-year shelf-life is not associated with embryo development, cumulative live birth, or neonatal outcomes such as birthweight or preterm birth.WHAT IS KNOWN ALREADYMedia composition, pH, and osmolality are recognized as important measures of media quality. In contrast, the shelf-life of culture media is poorly studied, resulting in different expiries among suppliers, with most between 120 days and 26 weeks. These differences have far-reaching implications, with the potential to affect success rates while increasing cost and waste. Most importantly, it is critical to know if 'old' media results in similar or worse IVF outcomes than 'fresh' media.STUDY DESIGN, SIZE, DURATIONA retrospective multicentre study was conducted using 9680 IVF/ICSI cycles from 6330 patients across eight clinics in Australia between October 2020 and December 2023.PARTICIPANTS/MATERIALS, SETTING, METHODSInclusion criteria were autologous cycles with ≥1 fertilized oocyte and known media production date. Cycles using thawed oocytes/embryos or non-standard transfer days were excluded. All embryos were cultured in time-lapse incubators using single-step media. Cycle outcomes, including embryo development, cumulative pregnancy, live birth, preterm birth, and birthweight for singleton, were analysed using unadjusted and adjusted regression models, as well as generalized estimating equation models to account for repeated measures within same patients.MAIN RESULTS AND THE ROLE OF CHANCEMedia age at use ranged from 38 to 365 days (mean ± SD: 190 ± 61 days). No statistically significant associations were observed between media age and embryo development outcomes, including percentage of Day 5/6 blastocysts (P = 0.389) and Day 5/6 usable blastocysts (P = 0.255). Similarly, media age was not associated with cumulative cycle outcomes including clinical pregnancy (P = 0.669), ongoing pregnancy (P = 0.986), or live birth (P = 0.257) in adjusted models. Subgroup analyses, including preimplantation genetic testing cycles and fresh transfers, yielded consistent results. Among 1070 singleton live births, media age was not associated with preterm birth (P = 0.818) or birthweight (P = 0.161).LIMITATIONS, REASONS FOR CAUTIONThis was a retrospective study based on a single medium type; results may not generalize to other formulations. Post-opening media handling was not captured, which may introduce unmeasured variability. Prospective studies are needed to confirm these findings across diverse media types and settings.WIDER IMPLICATIONS OF THE FINDINGSThese results support more flexible use of culture media up to expiration and suggest longer shelf-life media can be used to reduce waste and logistical burdens. Broader application could support susta
研究问题:在标记的1年保质期内,单步胚胎培养基的储存时间是否会影响胚胎发育、妊娠结局或体外受精的出生体重?保存期限为1年的单步胚胎培养基的龄期与胚胎发育、累计活产或新生儿结局(如出生体重或早产)无关。已知的内容媒体成分、pH值和渗透压被认为是衡量媒体质量的重要指标。相比之下,培养基的保质期研究较少,导致不同供应商的保质期不同,大多数在120天到26周之间。这些差异具有深远的影响,可能会影响成功率,同时增加成本和浪费。最重要的是,了解“旧”培养基与“新鲜”培养基的试管婴儿结果是否相似或更差是至关重要的。研究设计、规模、持续时间一项回顾性多中心研究于2020年10月至2023年12月在澳大利亚8个诊所的6330名患者中进行了9680个试管婴儿/ICSI周期。受试者/材料、环境、方法入选标准为:自体循环,受精卵细胞≥1个,培养基生产日期已知。排除使用解冻卵母细胞/胚胎或非标准移植天数的周期。所有胚胎均在单步培养基的延时培养箱中培养。周期结果,包括胚胎发育、累计妊娠、活产、早产和单胎出生体重,使用未调整和调整的回归模型以及广义估计方程模型进行分析,以解释同一患者的重复测量。主要结果及机会媒体的作用使用年龄范围为38 ~ 365天(平均±SD: 190±61天)。培养基年龄与第5/6天囊胚百分率(P = 0.389)和第5/6天可用囊胚百分率(P = 0.255)之间无统计学意义的相关性。同样,在调整后的模型中,中等年龄与包括临床妊娠(P = 0.669)、持续妊娠(P = 0.986)或活产(P = 0.257)在内的累积周期结局无关。亚组分析,包括植入前基因检测周期和新鲜移植,得出一致的结果。在1070例单胎活产中,中等年龄与早产(P = 0.818)或出生体重(P = 0.161)无关。局限性和谨慎的原因:这是一项基于单一培养基类型的回顾性研究;结果可能不能推广到其他配方。未捕获打开后的介质处理,这可能会引入无法测量的可变性。需要前瞻性研究在不同的媒体类型和环境中证实这些发现。研究结果的更广泛意义这些结果支持更灵活地使用培养基直至过期,并建议使用更长的保质期培养基来减少浪费和后勤负担。更广泛的应用可以支持试管婴儿实践的可持续性目标。研究经费/竞争利益(S)本研究没有经费。D.M.获得了Dawn-bio、Fujifilm Irvine Scientific和Overture Life的咨询费;以及Genea Biomedx和Organon的演讲费。其他作者声明没有利益冲突。试验注册号/ a。
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引用次数: 0
Studies of post-partum placentas provide insights into the origin of structural chromosomal aberrations. 产后胎盘的研究提供了对染色体结构畸变起源的见解。
IF 6.1 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-03 DOI: 10.1093/humrep/deaf235
S H Thomsen,A van Berkel,S van Veen,N van Koetsveld,M Joosten,K E M Diderich,M van den Born,M I Srebniak,D Van Opstal
STUDY QUESTIONCan comprehensive cytogenetic follow-up of the placenta post-partum uncover possible explanations for discrepancies between non-invasive prenatal testing (NIPT) showing structural chromosomal aberrations and foetal follow-up showing normal results or other chromosomal aberrations?SUMMARY ANSWERIn 18/31 (58%) cases of structural chromosomal aberrations detected with NIPT, where foetal and maternal follow-up was normal or the foetus had another chromosomal aberration, genome-wide examination of term placental chorionic villi confirmed the discrepancy and in 7/18 (39%) confirmed cases complex foeto-placental mosaicism was found.WHAT IS KNOWN ALREADYComplex chromosomal rearrangements are often seen in single-cell studies of preimplantation embryos, but it is unknown if these persist into the mature placenta. Confined placental mosaicism explains most discordant NIPTs involving a trisomy, but little is known about structural chromosome aberrations.STUDY DESIGN, SIZE, DURATIONWe performed a retrospective diagnostic test study of cytogenetic follow-up data from post-partum placentas. We included data from pregnancies where (i) NIPT showed a structural aberration, (ii) follow-up of foetus (amniotic fluid and/or cord blood) and mother (genomic DNA and/or cfDNA after birth) was normal or the foetus showed another chromosomal aberration, (iii) follow-up was performed in the Erasmus MC, (iv) more than one sample from the post-partum placenta was analysed, and (v) samples were of good quality (not in formaldehyde, sufficient material).In the period from January 2014 to March 2022, 115 231 NIPTs were performed in the Erasmus MC; 217 of these showed structural chromosomal aberrations and 123 were followed up in the Erasmus MC (inclusion criteria 3). After exclusion of the foetal (same aberration as with NIPT) and maternal structural chromosome aberrations, 48 placentas were requested to elucidate the discrepancies seen between NIPT (abnormal) and foetal karyotype (normal or differently abnormal; inclusion criteria 1-2). Of these, 31 met criteria 4 and 5 and were included in this study.PARTICIPANTS/MATERIALS, SETTING, METHODSIn a diagnostic setting, we performed a cytogenetic analysis of postpartum placentas in order to confirm confined placental mosaicism in 31 cases in which NIPT showed a structural chromosome aberration. Two to four chorionic villus biopsies were taken per placenta, and separated enzymatically into cytotrophoblast (CTB) and mesenchymal core (MC) and analysed using SNP arrays. In our analysis, cases were assessed for copy number variants ≥0.5 Mb and regions of homozygosity ≥3 Mb.MAIN RESULTS AND THE ROLE OF CHANCEIn 18/31 cases (58%), we could confirm the structural chromosome aberration detected with NIPT in one or more placental biopsies. In 13/31 cases (42%), the structural chromosomal aberration detected with NIPT was not confirmed, but in one case an apparently unrelated aberration was found in the CTB of two biopsies. In 11
研究问题:产后胎盘的全面细胞遗传学随访能否揭示显示结构性染色体畸变的无创产前检测(NIPT)与显示正常结果或其他染色体畸变的胎儿随访之间差异的可能解释?在18/31(58%)的NIPT检测到的结构性染色体畸变中,胎儿和母亲随访正常或胎儿有另一种染色体畸变,足月胎盘绒毛膜绒毛全基因组检查证实了这种差异,在7/18(39%)的确诊病例中发现复杂的胎胎盘嵌合体。已知情况:在胚胎着床前的单细胞研究中,复杂的染色体重排经常出现,但这些重排是否会持续到成熟的胎盘尚不清楚。局限的胎盘镶嵌现象解释了大多数涉及三体的不一致nipt,但对结构染色体畸变知之甚少。研究设计、大小、持续时间我们对产后胎盘的细胞遗传学随访数据进行了回顾性诊断试验研究。我们纳入了以下孕妇的数据:(i) NIPT显示结构畸变,(ii)胎儿(羊水和/或脐带血)和母亲(出生后的基因组DNA和/或cfDNA)的随访正常或胎儿显示另一种染色体畸变,(iii)在Erasmus MC中进行随访,(iv)对多个产后胎盘样本进行了分析,(v)样本质量好(不含甲醛,材料充足)。2014年1月至2022年3月,在Erasmus MC进行了115 231次nipt;其中217例出现结构性染色体畸变,123例在Erasmus MC中随访(纳入标准3)。在排除胎儿(与NIPT相同的畸变)和母体结构染色体畸变后,48个胎盘被要求阐明NIPT(异常)和胎儿核型(正常或不同异常;纳入标准1-2)之间的差异。其中31例符合标准4和5,纳入本研究。参与者/材料,环境,方法在诊断环境中,我们对产后胎盘进行了细胞遗传学分析,以确认31例NIPT表现出结构性染色体畸变的胎盘嵌合体。每个胎盘取2至4个绒毛膜绒毛活检,酶解分离成细胞滋养细胞(CTB)和间充质核(MC),并使用SNP阵列进行分析。在我们的分析中,评估病例的拷贝数变异≥0.5 Mb,纯合性区域≥3mb。在18/31例(58%)的胎盘活检中,我们可以证实NIPT检测到的结构染色体畸变。在13/31例(42%)的病例中,NIPT检测到的结构性染色体畸变未得到证实,但有一例在两次活检的CTB中发现明显无关的畸变。在11/18的确诊病例中,在胎盘中证实了与NIPT检测到的相同的畸变。所有这些病例都涉及染色体正常的胎儿,染色体畸变局限于胎盘。在一个病例中,在一个胎盘活检中发现了一个额外的,显然不相关的异常。在7/18的确诊病例中,NIPT检测到的畸变在胎盘中得到证实,并显示与涉及不同异常细胞系的复杂嵌合有关。在这7例中的4例中,胎儿受到不同于NIPT畸变的致病性染色体畸变的影响。在三个病例中,胎儿中存在相关但良性的染色体畸变。由于没有进行常规的核型、FISH或全基因组测序,我们只能假设在7例中看到的复杂的胎胎盘嵌合起源背后的机制,尽管文献中也有更有力的证据。研究结果的更广泛含义我们的结果有几个含义。首先,在NIPT后显示结构性染色体畸变的胎儿随访检查中,全基因组而不是靶向方法是有必要的,因为胎儿中的其他畸变可能被忽视。其次,对NIPT后出现染色体结构性畸变的怀孕夫妇进行咨询,不仅要关注NIPT检测到的特定畸变,还要关注胎儿可能存在另一种可能相关的结构畸变的可能性。此外,一个明显意义不确定的结构性染色体畸变可能会揭示胎儿本身真正的致病畸变,因此所有潜在的胎儿结构性染色体畸变病例都应随访。 第三,我们展示了胎盘的全面检查,特别是CTB和MC的分离,如何为胚胎起源和结构染色体畸变背后的机制提供重要的见解。最后,我们的研究结果表明,在胚胎着床前的单细胞研究中经常看到的复杂染色体重排不是人工产物,而是一种生物学现象,实际上可以持续到成熟的胎盘和胎儿。研究资金/竞争利益(S)Simon H. Thomsen由私人研究捐赠和奥胡斯大学临床医学系资助。所有作者声明无利益冲突。试验注册号/ a。
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Human reproduction
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