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
{"title":"Recommendations from the WHO guideline for the prevention, diagnosis, and treatment of infertility†.","authors":"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","doi":"10.1093/humrep/deaf212","DOIUrl":"10.1093/humrep/deaf212","url":null,"abstract":"<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","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"25-38"},"PeriodicalIF":6.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12769440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632732","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}
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}
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
{"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}
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
{"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}
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
{"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}
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。
{"title":"Testing the efficacy of a self-guided psychotherapy intervention for infertility-related distress: a randomized controlled trial.","authors":"M M L Poulter,T D Wahl,M J Kiviharju,T S Campbell,J L Gordon","doi":"10.1093/humrep/deaf237","DOIUrl":"https://doi.org/10.1093/humrep/deaf237","url":null,"abstract":"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","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"50 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765037","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}
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
{"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}
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
{"title":"Semen analysis as a biomarker of male aging: biological mechanisms, clinical implications, and public health perspectives.","authors":"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","doi":"10.1093/humrep/deaf232","DOIUrl":"https://doi.org/10.1093/humrep/deaf232","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717522","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}
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
{"title":"Culture media age does not affect IVF outcomes.","authors":"Dean E Morbeck,Natalie Hesketh,Diana Bui","doi":"10.1093/humrep/deaf236","DOIUrl":"https://doi.org/10.1093/humrep/deaf236","url":null,"abstract":"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","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717523","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 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
{"title":"Studies of post-partum placentas provide insights into the origin of structural chromosomal aberrations.","authors":"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","doi":"10.1093/humrep/deaf235","DOIUrl":"https://doi.org/10.1093/humrep/deaf235","url":null,"abstract":"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","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"18 2 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664283","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}