L Jacxsens, G Pennings, L Lentacker, D Stoop, V Provoost
<p><strong>Study question: </strong>What information does an international group of professionals and egg donors consider relevant and morally necessary for prospective egg donors to provide valid informed consent?</p><p><strong>Summary answer: </strong>Participants considered 80% of all concrete information items (CIIs) to be relevant (e.g. all legal aspects) and 67% to be morally necessary.</p><p><strong>What is known already: </strong>Studies indicate that egg donors are not always adequately informed and have expressed a desire for more comprehensive information. This highlights the need for a comprehensive guideline of essential information for prospective egg donors.</p><p><strong>Study design, size, duration: </strong>This modified Delphi study used a survey in an iterative process of three rounds to reach a consensus on what information items are relevant and morally necessary for a valid informed consent of candidate egg donors. Invitations to participate were sent out in November 2023 and the final round closed in November 2024.</p><p><strong>Participants/materials, setting, methods: </strong>The 35 participants were experienced egg donors and professionals from a range of disciplines (social and medical sciences, bioethics, psychology, fertility medicine and law) from 14 countries. The survey consisted of 13 categories and 133 CIIs, which participants scored for relevance via a 4-point Likert scale and moral necessity on a dichotomous scale (yes/no). Content Validity Index (CVI) was calculated for measuring relevance and percentage of agreement for moral necessity. A comment section was available.</p><p><strong>Main results and the role of chance: </strong>Consensus was indicated as an I-CVI (CVI per item) of 0.78 or higher. The same cut-off was used to indicate consensus for moral necessity. For 27 out of 133 CIIs, the I-CVI was lower than 0.78. The percentage of moral necessity was below 0.78 for 44 CIIs. Four CIIs reached a I-CVI of 1: all experts thought it was relevant for a candidate donor to know (i) the need to undergo ovarian stimulation and (ii) a retrieval procedure, as well as (iii) her legal rights over the donated eggs after the retrieval procedure and (iv) her legal right to withdraw consent. The latter is the only CII that scored 100% on moral necessity. The CII with the lowest I-CVI is 'The family type and characteristics of the potential recipients of the donor eggs' (0.32). The CII with the lowest percentage of agreement for moral necessity was 'An egg donor's social circle might give negative feedback/opinions on the donation' (36.36%). In several categories (e.g. 'Physical side-effects and risks'), almost all CIIs reached a consensus among experienced egg donors, bioethicists, and humanities and social sciences experts, while hardly any CII reached a consensus among fertility experts, lawyers, and academic medical doctors.</p><p><strong>Limitations, reasons for caution: </strong>Despite our efforts, we were unable
{"title":"Identifying essential information for a valid informed consent of egg donors: an international Delphi study.","authors":"L Jacxsens, G Pennings, L Lentacker, D Stoop, V Provoost","doi":"10.1093/humrep/deaf176","DOIUrl":"10.1093/humrep/deaf176","url":null,"abstract":"<p><strong>Study question: </strong>What information does an international group of professionals and egg donors consider relevant and morally necessary for prospective egg donors to provide valid informed consent?</p><p><strong>Summary answer: </strong>Participants considered 80% of all concrete information items (CIIs) to be relevant (e.g. all legal aspects) and 67% to be morally necessary.</p><p><strong>What is known already: </strong>Studies indicate that egg donors are not always adequately informed and have expressed a desire for more comprehensive information. This highlights the need for a comprehensive guideline of essential information for prospective egg donors.</p><p><strong>Study design, size, duration: </strong>This modified Delphi study used a survey in an iterative process of three rounds to reach a consensus on what information items are relevant and morally necessary for a valid informed consent of candidate egg donors. Invitations to participate were sent out in November 2023 and the final round closed in November 2024.</p><p><strong>Participants/materials, setting, methods: </strong>The 35 participants were experienced egg donors and professionals from a range of disciplines (social and medical sciences, bioethics, psychology, fertility medicine and law) from 14 countries. The survey consisted of 13 categories and 133 CIIs, which participants scored for relevance via a 4-point Likert scale and moral necessity on a dichotomous scale (yes/no). Content Validity Index (CVI) was calculated for measuring relevance and percentage of agreement for moral necessity. A comment section was available.</p><p><strong>Main results and the role of chance: </strong>Consensus was indicated as an I-CVI (CVI per item) of 0.78 or higher. The same cut-off was used to indicate consensus for moral necessity. For 27 out of 133 CIIs, the I-CVI was lower than 0.78. The percentage of moral necessity was below 0.78 for 44 CIIs. Four CIIs reached a I-CVI of 1: all experts thought it was relevant for a candidate donor to know (i) the need to undergo ovarian stimulation and (ii) a retrieval procedure, as well as (iii) her legal rights over the donated eggs after the retrieval procedure and (iv) her legal right to withdraw consent. The latter is the only CII that scored 100% on moral necessity. The CII with the lowest I-CVI is 'The family type and characteristics of the potential recipients of the donor eggs' (0.32). The CII with the lowest percentage of agreement for moral necessity was 'An egg donor's social circle might give negative feedback/opinions on the donation' (36.36%). In several categories (e.g. 'Physical side-effects and risks'), almost all CIIs reached a consensus among experienced egg donors, bioethicists, and humanities and social sciences experts, while hardly any CII reached a consensus among fertility experts, lawyers, and academic medical doctors.</p><p><strong>Limitations, reasons for caution: </strong>Despite our efforts, we were unable ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2136-2147"},"PeriodicalIF":6.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Ovarian stimulation with follitropin delta for in vitro fertilization: a multicentre, randomized, assessor-blind comparison with follitropin alfa using conventional dosing regimens (ADAPT-1 trial).","authors":"","doi":"10.1093/humrep/deaf185","DOIUrl":"10.1093/humrep/deaf185","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2207-2208"},"PeriodicalIF":6.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12584916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091601","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}
J Smeenk, C Wyns, Ch De Geyter, M S Kupka, C Bergh, I Cuevas Saiz, D De Neubourg, K Rezabek, A Tandler-Schneider, I Rugescu, V Goossens
Study question: What are the data and trends of ART and IUI cycle numbers and their outcomes, and of fertility preservation (FP) interventions, reported in 2020 as compared to previous years?
Summary answer: This 24th ESHRE report highlights the number of ART treatment cycles and children born over the years, showing a decline in the total number of treatment cycles, when comparing 2020 with 2019, alongside a decline in twin deliveries owing to a decrease in transfers of multiple embryos; however, fresh IVF or ICSI cycles and frozen embryo transfers (FET) showed similar pregnancy rates, and the reported IUI cycle numbers decreased while maintaining stable outcomes.
What is known already: ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF Monitoring (EIM) consortium since 1997 and reported in a total of 23 manuscripts published in Human Reproduction and Human Reproduction Open.
Study design, size, duration: Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between January 1 and December 31, 2020, were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in the 44 countries that are members of the EIM Consortium.
Participants/materials, setting, methods: Overall, 1440 clinics offering ART services in 41 countries reported 923 318 treatment cycles (-14%; in 2019: 1 077 813), including 135 231 with IVF, 356 408 with ICSI, 305 373 with FET, 57 051 with preimplantation genetic testing (PGT), 64 007 with oocyte donation, 353 with IVM of oocytes, and 4895 cycles using frozen oocytes. A total of 1288 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 112 663) or donor semen (IUI-D; n = 38 839) in 30 and 21 countries, respectively. Sixteen countries reported 29 566 interventions in pre-and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking.
Main results and the role of chance: In 24 countries (21 in 2019) in which all ART clinics reported to the registry, 356 427 treatment cycles were registered for a total population of approximately 268 million inhabitants in these countries, allowing the best estimate of a mean of 1330 cycles performed per million inhabitants (range: 142-3230). Among the reporting countries, for IVF, the clinical pregnancy rates (PR) per aspiration were similar to that in 2019 (22.1% versus 21.8% in 2019). For ICSI, the corresponding PRs showed similar trends (20.0% in 2020 versus 20.2% in 2019). When freeze-all cycles were excluded from the calculations, the clinical PRs per aspiration were 26.4% (28.5% in 2019) and 25.6% (26.2% in 20
{"title":"ART in Europe, 2020: results generated from European registries by ESHRE†.","authors":"J Smeenk, C Wyns, Ch De Geyter, M S Kupka, C Bergh, I Cuevas Saiz, D De Neubourg, K Rezabek, A Tandler-Schneider, I Rugescu, V Goossens","doi":"10.1093/humrep/deaf179","DOIUrl":"10.1093/humrep/deaf179","url":null,"abstract":"<p><strong>Study question: </strong>What are the data and trends of ART and IUI cycle numbers and their outcomes, and of fertility preservation (FP) interventions, reported in 2020 as compared to previous years?</p><p><strong>Summary answer: </strong>This 24th ESHRE report highlights the number of ART treatment cycles and children born over the years, showing a decline in the total number of treatment cycles, when comparing 2020 with 2019, alongside a decline in twin deliveries owing to a decrease in transfers of multiple embryos; however, fresh IVF or ICSI cycles and frozen embryo transfers (FET) showed similar pregnancy rates, and the reported IUI cycle numbers decreased while maintaining stable outcomes.</p><p><strong>What is known already: </strong>ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF Monitoring (EIM) consortium since 1997 and reported in a total of 23 manuscripts published in Human Reproduction and Human Reproduction Open.</p><p><strong>Study design, size, duration: </strong>Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between January 1 and December 31, 2020, were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in the 44 countries that are members of the EIM Consortium.</p><p><strong>Participants/materials, setting, methods: </strong>Overall, 1440 clinics offering ART services in 41 countries reported 923 318 treatment cycles (-14%; in 2019: 1 077 813), including 135 231 with IVF, 356 408 with ICSI, 305 373 with FET, 57 051 with preimplantation genetic testing (PGT), 64 007 with oocyte donation, 353 with IVM of oocytes, and 4895 cycles using frozen oocytes. A total of 1288 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 112 663) or donor semen (IUI-D; n = 38 839) in 30 and 21 countries, respectively. Sixteen countries reported 29 566 interventions in pre-and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking.</p><p><strong>Main results and the role of chance: </strong>In 24 countries (21 in 2019) in which all ART clinics reported to the registry, 356 427 treatment cycles were registered for a total population of approximately 268 million inhabitants in these countries, allowing the best estimate of a mean of 1330 cycles performed per million inhabitants (range: 142-3230). Among the reporting countries, for IVF, the clinical pregnancy rates (PR) per aspiration were similar to that in 2019 (22.1% versus 21.8% in 2019). For ICSI, the corresponding PRs showed similar trends (20.0% in 2020 versus 20.2% in 2019). When freeze-all cycles were excluded from the calculations, the clinical PRs per aspiration were 26.4% (28.5% in 2019) and 25.6% (26.2% in 20","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2038-2055"},"PeriodicalIF":6.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124579","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}
Hartmut Cuny,Antonia W Shand,Jennifer Goth,Delicia Z Sheng,Tamarah Tossey,Ella M M A Martin,Alena Sipka,Olga Aleshin,Francisco J Schneuer,Natasha Nassar,Sally L Dunwoodie
STUDY QUESTIONDo women with a history of recurrent miscarriage have altered nicotinamide adenine dinucleotide (NAD)-related metabolites that can be detected in blood, plasma, or urine samples?SUMMARY ANSWERWomen with a history of recurrent miscarriage have higher blood, plasma, and urine concentrations of NAD Salvage Pathway excretion products, and urinary excretion of nicotinamide (NAM) is also elevated, compared to control women.WHAT IS KNOWN ALREADYRecurrent miscarriage risk is associated with advancing age, high and low BMI, dietary factors, various medical conditions including inflammation, as well as environmental exposures, e.g. to chemicals and pollution. Perturbation of NAD synthesis due to genetic and/or environmental factors causes NAD deficiency, which is implicated in Congenital NAD Deficiency Disorder (CNDD) characterized by recurrent pregnancy loss and congenital anomalies. In CNDD mouse models, foetal anomalies and embryo loss are prevented if NAD levels are raised by supplementing the mother's diet with an NAD precursor, such as vitamin B3, during pregnancy.STUDY DESIGN, SIZE, DURATIONThis prospective pilot cohort study included 88 non-pregnant women between 20 and 40 years of age, 37 with and 51 without a history of recurrent miscarriage. Recurrent miscarriage was defined as a history of two or more consecutive spontaneous miscarriages <20 weeks' gestation, with the last miscarriage between 6 weeks and 2 years prior to recruitment. The study was conducted at the Royal Hospital for Women, Sydney, Australia, between March 2022 and December 2023.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants completed a questionnaire about their socio-demographic characteristics, health, lifestyle, diet, medication, and vitamin use; and provided morning fasting blood and urine samples. Levels of NAD and 25 related metabolites were measured in whole blood, plasma, and urine using a validated ultra-high performance liquid chromatography-tandem mass spectrometry method. Differences in NAD metabolism between the groups were assessed by volcano plots and partial least-squares discriminant analysis. Characteristics of women between the two groups were compared using chi-squared statistics. Multivariable generalized additive models were used to assess the association between NAD metabolites and miscarriage. Predictive accuracy of metabolites alone and with age was examined using three machine learning models, including Logistic Regression, Random Forest, and Gradient Boosting Classifier and assessed using the area under the receiver operating characteristic curve (AUROC).MAIN RESULTS AND THE ROLE OF CHANCEElevated levels of the metabolites 1-methylnicotinamide (1MNA), N-methyl-2-pyridone-5-carboxamide (2PY), and N-methyl-4-pyridone-3-carboxamide (4PY), representing excretion metabolites of the NAD Salvage Pathway, were associated with a higher risk of recurrent miscarriage. These metabolites showed a strong positive correlation among the three teste
研究问题：有复发性流产史的女性是否在血液、血浆或尿液样本中检测到烟酰胺腺嘌呤二核苷酸（NAD）相关代谢物的改变？有复发性流产史的女性血液、血浆和尿液中NAD回收途径排泄产物的浓度较高，与对照组相比，尿中烟酰胺（NAM）的排泄量也升高。已知情况复发性流产风险与年龄增长、BMI高低、饮食因素、包括炎症在内的各种医疗条件以及环境暴露（如化学品和污染）有关。由于遗传和/或环境因素导致NAD合成的干扰导致NAD缺乏，这与先天性NAD缺乏性障碍（CNDD）有关，其特征是反复妊娠丢失和先天性异常。在CNDD小鼠模型中，如果在怀孕期间通过在母亲的饮食中添加NAD前体（如维生素B3）来提高NAD水平，则可以防止胎儿异常和胚胎丢失。研究设计、规模、持续时间这项前瞻性先导队列研究包括88名20 - 40岁的未怀孕妇女，其中37名有复发性流产史，51名无复发性流产史。复发性流产定义为妊娠<20周连续两次或两次以上自然流产，最后一次流产发生在招募前6周至2年之间。该研究于2022年3月至2023年12月在澳大利亚悉尼皇家妇女医院进行。参与者/材料，环境，方法参与者完成一份关于他们的社会人口特征、健康、生活方式、饮食、药物和维生素使用的调查问卷；并提供了空腹血样和尿样。采用高效液相色谱-串联质谱法测定全血、血浆和尿液中NAD和25种相关代谢物的水平。通过火山图和偏最小二乘判别分析评估各组之间NAD代谢的差异。采用卡方统计比较两组女性的特征。使用多变量广义加性模型来评估NAD代谢物与流产之间的关系。使用三种机器学习模型（包括Logistic回归、随机森林和梯度增强分类器）检查代谢物单独和随年龄变化的预测准确性，并使用受试者工作特征曲线下面积（AUROC）进行评估。主要结果和机会的作用：代谢产物1-甲基烟酰胺（1MNA）、n -甲基-2-吡酮-5-羧酰胺（2PY）和n -甲基-4-吡酮-3-羧酰胺（4PY）水平升高，代表NAD挽救途径的排泄代谢产物，与复发性流产的高风险相关。这些代谢物在三种被测生物基质之间显示出强烈的正相关，证实了这三种基质对这些标记物的量化的适用性。反复流产妇女的全血邻氨基苯酸和尿NAM水平也升高。单因素分析显示，血浆中1MNA与复发性流产相关，考虑到产妇年龄后，其影响持续存在（校正优势比1.02;95% CI 1.01, 1.03）， 1MNA每增加1个单位，流产的几率增加2%。当模型中包含所有三种代谢物1MNA、2PY和4PY以及年龄时，使用机器学习方法的预测准确性最高（AUROC 0.89; 95% CI 0.83, 0.95）。本研究仅在一家医院进行，保证了较高的内部效度，但可能会限制外部效度。样本量很小，研究结果应该在更大规模的研究中得到重复。测量到的与nada相关的代谢物水平代表了样本收集时的一个快照，但可能不能反映妇女怀孕的时间。研究结果的更广泛意义：一项新发现表明，复发性流产妇女的非甾体抗炎肽及其衍生产物的排泄量升高，表明非甾体抗炎肽合成途径的差异与不良妊娠结局有关。两组血液循环和尿液中2PY和4PY水平的显著差异表明，这些代谢物是与复发性流产相关的潜在生物标志物。与不良妊娠结局相关的几种情况也会影响NAD代谢并导致这些代谢物水平升高。因此，这些代谢物可能不仅仅是生物标志物，而且在许多复发性流产病例中也是潜在机制的指标。需要进一步评估其他人群中复发性流产妇女的NAD代谢以及包括饮食在内的其他关联。 研究经费/竞争利益(S)本研究由国家卫生与医学研究委员会（NHMRC），主要研究奖学金（ID1135886），领导级3奖学金（ID2007896）和项目资助（ID1162878）资助。新南威尔士州（NSW）健康心血管研究能力计划高级研究员补助金；Key基金会、Ross信托基金以及Steven和Linda Harker夫妇的慈善支持。N.N.得到了NHMRC领导一级奖学金（ID1197940）和儿童金融市场基金会的支持。我们感谢由新南威尔士州政府资助的张维德心脏研究所创新中心，以及弗里德曼基金会对代谢组学设施的资助。作者声明无利益冲突。试验注册号/ a。
{"title":"Identification of potential NAD-related biomarkers of recurrent miscarriage risk.","authors":"Hartmut Cuny,Antonia W Shand,Jennifer Goth,Delicia Z Sheng,Tamarah Tossey,Ella M M A Martin,Alena Sipka,Olga Aleshin,Francisco J Schneuer,Natasha Nassar,Sally L Dunwoodie","doi":"10.1093/humrep/deaf195","DOIUrl":"https://doi.org/10.1093/humrep/deaf195","url":null,"abstract":"STUDY QUESTIONDo women with a history of recurrent miscarriage have altered nicotinamide adenine dinucleotide (NAD)-related metabolites that can be detected in blood, plasma, or urine samples?SUMMARY ANSWERWomen with a history of recurrent miscarriage have higher blood, plasma, and urine concentrations of NAD Salvage Pathway excretion products, and urinary excretion of nicotinamide (NAM) is also elevated, compared to control women.WHAT IS KNOWN ALREADYRecurrent miscarriage risk is associated with advancing age, high and low BMI, dietary factors, various medical conditions including inflammation, as well as environmental exposures, e.g. to chemicals and pollution. Perturbation of NAD synthesis due to genetic and/or environmental factors causes NAD deficiency, which is implicated in Congenital NAD Deficiency Disorder (CNDD) characterized by recurrent pregnancy loss and congenital anomalies. In CNDD mouse models, foetal anomalies and embryo loss are prevented if NAD levels are raised by supplementing the mother's diet with an NAD precursor, such as vitamin B3, during pregnancy.STUDY DESIGN, SIZE, DURATIONThis prospective pilot cohort study included 88 non-pregnant women between 20 and 40 years of age, 37 with and 51 without a history of recurrent miscarriage. Recurrent miscarriage was defined as a history of two or more consecutive spontaneous miscarriages <20 weeks' gestation, with the last miscarriage between 6 weeks and 2 years prior to recruitment. The study was conducted at the Royal Hospital for Women, Sydney, Australia, between March 2022 and December 2023.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants completed a questionnaire about their socio-demographic characteristics, health, lifestyle, diet, medication, and vitamin use; and provided morning fasting blood and urine samples. Levels of NAD and 25 related metabolites were measured in whole blood, plasma, and urine using a validated ultra-high performance liquid chromatography-tandem mass spectrometry method. Differences in NAD metabolism between the groups were assessed by volcano plots and partial least-squares discriminant analysis. Characteristics of women between the two groups were compared using chi-squared statistics. Multivariable generalized additive models were used to assess the association between NAD metabolites and miscarriage. Predictive accuracy of metabolites alone and with age was examined using three machine learning models, including Logistic Regression, Random Forest, and Gradient Boosting Classifier and assessed using the area under the receiver operating characteristic curve (AUROC).MAIN RESULTS AND THE ROLE OF CHANCEElevated levels of the metabolites 1-methylnicotinamide (1MNA), N-methyl-2-pyridone-5-carboxamide (2PY), and N-methyl-4-pyridone-3-carboxamide (4PY), representing excretion metabolites of the NAD Salvage Pathway, were associated with a higher risk of recurrent miscarriage. These metabolites showed a strong positive correlation among the three teste","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: O-020 Impact of an oral antioxidant supplement in men on semen quality and pregnancy rates, results of a multicentre, randomised, triple-blind, placebo-controlled trial (SUMMER trial).","authors":"","doi":"10.1093/humrep/deaf213","DOIUrl":"https://doi.org/10.1093/humrep/deaf213","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"105 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373766","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 QUESTIONIs the non-pronuclear (0PN) fertilization pattern, as assessed by single static observation during the 16- to 18-h post-insemination (hpi) interval, compatible with embryo developmental competence?SUMMARY ANSWERA few zygotes show pronuclei (PN) solely outside the static fertilization assessment time interval and can develop to blastocyst stage, while rare cases of cleavage without pronuclear formation always result in early developmental arrest or degeneration.WHAT IS KNOWN ALREADYRecently, the use of atypically pronucleated zygotes-showing no, one, or three PN (0PN, 1PN, and 3PN), or other less frequent patterns-has been increasingly proposed as a measure to maximize the number of embryos available for treatment and the cumulative clinical outcome per cycle. The use of such zygotes poses important clinical and ethical concerns; it also raises scientific questions, such as the hypothesis that the 0PN pattern can be compatible with pre- and post-implantation development in the absence of actual formation of PN. Allowing detailed observation of embryo morphokinetics, time-lapse technology (TLT) can be decisive in resolving such questions.STUDY DESIGN, SIZE, DURATIONRetrospective observational study (2013-2020) including 6035 oocytes inseminated by ICSI and cultured in a time-lapse imaging incubator system. Zygotes (N = 4479), classified by PN-type, were divided into sub-groups based on timings of PN appearance (tPNa: <16hpi, >16hpi) and PN fading (tPNf: <16hpi, 16-18hpi, 18-20hpi, >20hpi). Their development was monitored until blastocyst stage. The remaining 1556 injected oocytes were either degenerated (N = 801) or did not show PN (true-0PN; N = 755). Among the latter, 186 showed ≥1 cleavage(s) and then degenerated. Their videos were analysed to assess events preceding developmental arrest.PARTICIPANTS/MATERIALS, SETTING, METHODSOvarian stimulation with GnRH-antagonist and hCG/agonist trigger was performed, with all patients undergoing ICSI and blastocyst culture. The study endpoints were the blastulation rates across different PN-appearance and -fading thresholds, as well as a thorough description of the events during cell division(s) in 0PN embryos that experienced early arrest. Regression analyses were conducted, adjusting for confounders such as maternal age, male factor, and PN-type, with associations confirmed using generalized estimating equations.MAIN RESULTS AND ROLE OF CHANCEZygotes showing two PN (2PN, N = 4479) monitored by TLT were distributed in sub-groups based on tPNf (<16 hpi, N = 11; 16-18 hpi, N = 44; 18-20 hpi, N = 309; >20 hpi, N = 4115). In a few cases (N = 85), PN formation occurred after 16 hpi, up until 31 hpi. Single static observation during the 16- to 18-hpi conventional interval would have missed the zygotes undergoing very early PNf and at least part of those undergoing late PNa. Comparison between the above sub-groups showed that pronuclear fading occurring at 18-20 hpi was associated with the highest b
{"title":"Embryos not showing pronuclei by single static observation arise from atypical pronuclear dynamics or rare unfertilized oocytes with abortive cleavage behaviour.","authors":"Giovanni Coticchio,Marilena Taggi,Francesca Asturi,Alfredo Stati,Maria Bordignon,Federica Innocenti,Gaia Saturno,Alberto Vaiarelli,Laura Rienzi,Danilo Cimadomo","doi":"10.1093/humrep/deaf199","DOIUrl":"https://doi.org/10.1093/humrep/deaf199","url":null,"abstract":"STUDY QUESTIONIs the non-pronuclear (0PN) fertilization pattern, as assessed by single static observation during the 16- to 18-h post-insemination (hpi) interval, compatible with embryo developmental competence?SUMMARY ANSWERA few zygotes show pronuclei (PN) solely outside the static fertilization assessment time interval and can develop to blastocyst stage, while rare cases of cleavage without pronuclear formation always result in early developmental arrest or degeneration.WHAT IS KNOWN ALREADYRecently, the use of atypically pronucleated zygotes-showing no, one, or three PN (0PN, 1PN, and 3PN), or other less frequent patterns-has been increasingly proposed as a measure to maximize the number of embryos available for treatment and the cumulative clinical outcome per cycle. The use of such zygotes poses important clinical and ethical concerns; it also raises scientific questions, such as the hypothesis that the 0PN pattern can be compatible with pre- and post-implantation development in the absence of actual formation of PN. Allowing detailed observation of embryo morphokinetics, time-lapse technology (TLT) can be decisive in resolving such questions.STUDY DESIGN, SIZE, DURATIONRetrospective observational study (2013-2020) including 6035 oocytes inseminated by ICSI and cultured in a time-lapse imaging incubator system. Zygotes (N = 4479), classified by PN-type, were divided into sub-groups based on timings of PN appearance (tPNa: <16hpi, >16hpi) and PN fading (tPNf: <16hpi, 16-18hpi, 18-20hpi, >20hpi). Their development was monitored until blastocyst stage. The remaining 1556 injected oocytes were either degenerated (N = 801) or did not show PN (true-0PN; N = 755). Among the latter, 186 showed ≥1 cleavage(s) and then degenerated. Their videos were analysed to assess events preceding developmental arrest.PARTICIPANTS/MATERIALS, SETTING, METHODSOvarian stimulation with GnRH-antagonist and hCG/agonist trigger was performed, with all patients undergoing ICSI and blastocyst culture. The study endpoints were the blastulation rates across different PN-appearance and -fading thresholds, as well as a thorough description of the events during cell division(s) in 0PN embryos that experienced early arrest. Regression analyses were conducted, adjusting for confounders such as maternal age, male factor, and PN-type, with associations confirmed using generalized estimating equations.MAIN RESULTS AND ROLE OF CHANCEZygotes showing two PN (2PN, N = 4479) monitored by TLT were distributed in sub-groups based on tPNf (<16 hpi, N = 11; 16-18 hpi, N = 44; 18-20 hpi, N = 309; >20 hpi, N = 4115). In a few cases (N = 85), PN formation occurred after 16 hpi, up until 31 hpi. Single static observation during the 16- to 18-hpi conventional interval would have missed the zygotes undergoing very early PNf and at least part of those undergoing late PNa. Comparison between the above sub-groups showed that pronuclear fading occurring at 18-20 hpi was associated with the highest b","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"26 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370638","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}
D C Kieslinger,C G Vergouw,F von Estorff,L Ramos,B Arends,M H J M Curfs,E Slappendel,E H Kostelijk,M H E C Pieters,D Consten,M O Verhoeven,D E Besselink,F Broekmans,B J Cohlen,J M J Smeenk,S Mastenbroek,C H de Koning,Y M van Kasteren,E Moll,J van Disseldorp,E A Brinkhuis,E A M Kuijper,W M van Baal,H G I van Weering,P J Q van der Linden,M H Gerards,P M Bossuyt,M van Wely,C B Lambalk
STUDY QUESTIONDoes uninterrupted culture in a time-lapse incubator with or without a commercially available machine learning embryo selection algorithm result in comparable obstetric and perinatal outcomes as interrupted culture and morphological embryo selection?SUMMARY ANSWERThe application of uninterrupted culture in a time-lapse incubator with and without the use of an embryo selection algorithm is comparable to interrupted embryo culture and morphological embryo selection in terms of obstetric and perinatal results.WHAT IS KNOWN ALREADYThere is very limited evidence regarding the safety of time-lapse monitoring (TLM) from prospective randomized controlled trials (RCT). Recent RCTs have demonstrated that the application of TLM does not increase (cumulative) live birth rates or shorten the time to pregnancy within 1 year. Although most studies only report pregnancy rates, the safety of this commonly used method is also relevant for decision-making.STUDY DESIGN, SIZE, DURATIONThe obstetric and perinatal outcomes of patients scheduled for Day 3 single embryo transfer who participated in a multicentre RCT on TLM were studied (SelecTIMO trial). Three groups were compared: (i) TLE: embryo selection based on a commercially available Day 3 TLM algorithm, used adjunctively with morphology, and uninterrupted culture. (ii) TLR: routine morphological embryo selection and uninterrupted culture. (iii) CON: routine morphological embryo selection and interrupted culture.PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 1731 IVF/ICSI patients undergoing their first, second, or third oocyte retrieval cycle were randomized. Obstetric and perinatal data were registered for all pregnancies occurring after fresh and frozen embryo transfers associated with the initial oocyte retrieval cycle as well as natural conceptions within 1 year. Serious pregnancy complications and birth weight were considered main safety outcomes. Mean differences (MD) and age-adjusted relative risks (RRadj) and mean differences with 95% CI were calculated for TLE and TLR versus CON.MAIN RESULTS AND THE ROLE OF CHANCEA total of 827 women gave birth to a singleton during the follow-up period (TLE = 275, TLR = 278, CON = 274; P = 0.99). Of the 827 women who gave birth to a singleton, 497 deliveries originated from a fresh embryo transfer (60%), 294 from a frozen embryo transfer (36%), and 36 women conceived naturally (4%), with similar proportions in each study group. The proportion of women with serious pregnancy complications was comparable across the three groups (TLE vs CON: RRadj 0.95, 95% CI 0.65-1.40 and TLR vs CON: RRadj 1.03, 95% CI 0.70-1.50; P = 0.89). Mean (SD) gestational age at birth was 39.4 (1.9) weeks, 39.5 (1.5) weeks, and 39.3 (1.9) weeks, respectively. We found no evidence of differences in preterm and very preterm births between groups. Mean (SD) weight at birth was 3413 (588) g, 3412 (588) g, and 3377 (578) g, respectively (TLE vs CON: MD 34, 95% CI -62 to 129 and TLR vs
研究问题：在延时培养箱中进行不间断培养，有无市售机器学习胚胎选择算法，是否会导致与中断培养和形态胚胎选择相当的产科和围产期结果？在延时培养箱中不间断培养的应用，无论是否使用胚胎选择算法，在产科和围产期结果方面与中断胚胎培养和形态胚胎选择相当。从前瞻性随机对照试验（RCT）中得到的关于延时监测（TLM）安全性的证据非常有限。最近的随机对照试验表明，TLM的应用不会增加（累积）活产率或缩短1年内的妊娠时间。虽然大多数研究只报告了怀孕率，但这种常用方法的安全性也与决策有关。研究设计、规模、持续时间：我们研究了参加TLM多中心随机对照试验、计划进行第3天单胚胎移植的患者的产科和围产期结局（SelecTIMO试验）。三组比较：(i) TLE：基于市售的第3天TLM算法进行胚胎选择，使用形态学辅助，不间断培养。（ii） TLR：常规形态胚胎选择和不间断培养。（iii） CON：常规形态胚胎选择和中断培养。参与者/材料、环境、方法共随机选取1731例接受第一、第二或第三个卵母细胞回收周期的IVF/ICSI患者。产科和围产期数据记录了所有在新鲜和冷冻胚胎移植后与初始卵母细胞回收周期以及1年内自然受孕相关的妊娠。严重的妊娠并发症和出生体重被认为是主要的安全结局。计算TLE和TLR与CON的平均差异（MD）、年龄调整相对危险度（RRadj）和95% CI的平均差异。主要结果和机会的作用随访期间，共有827名妇女生了一胎（TLE = 275, TLR = 278, CON = 274; P = 0.99）。在827名生育单胎的妇女中，497名分娩来自新鲜胚胎移植（60%），294名来自冷冻胚胎移植（36%），36名妇女自然受孕（4%），每个研究组的比例相似。三组发生严重妊娠并发症的妇女比例具有可比性（TLE vs CON: RRadj 0.95, 95% CI 0.65-1.40, TLR vs CON: RRadj 1.03, 95% CI 0.70-1.50; P = 0.89）。出生时平均胎龄（SD）分别为39.4（1.9）周、39.5（1.5）周和39.3（1.9）周。我们没有发现两组早产儿和非常早产儿的差异。出生时的平均体重（SD）分别为3413 (588)g、3412 (588)g和3377 (578)g （TLE vs CON: MD 34, 95% CI -62至129，TLR vs CON: MD 32, 95% CI -635至120，P = 0.70）。我们没有观察到低出生体重和非常低出生体重的婴儿有实质性的差异。分娩后立即出现健康问题的婴儿有8名，TLR组有12名，CON组有11名。TLE组4例，TLR组4例，CON组7例。TLE组5例，TLR组3例，CON组5例。本研究报告了一种延时培养箱的安全结果，然而，目前有更多的系统可用。研究结果表明，在产科和围产期风险方面，与中断胚胎培养和常规形态选择相比，不间断延时培养（包括和不包括基于机器学习的胚胎选择）可被认为是安全的。研究经费/竞争利益(S)作者获得了荷兰卫生研究与发展组织（ZonMw）的资助，用于开展SelecTIMO研究（卫生保健效率研究计划资助843001602）。默克公司（德国和荷兰）提供了6台延时培养箱，资助了实验室的调整，并在研究前和研究期间为实验室人员提供了技术支持和培训。D.C.K.获得澳大利亚生育学会交流奖。以下利益声明是在提交的工作之外做出的：F.B.报告了来自Besins Healthcare Monaco对LUMO试验的额外财政支持，默克公司对正在进行的基础研究的奖学金资助，默克公司、Besins和Ferring公司的咨询费和付款或酬金，并且是英国POISE研究的DSMB成员。J.M.J.S. 已收到Ferring BV和默克的赠款或合同（两种情况下均支付给ETZ）；fering BV向顾问委员会收取的咨询费；默克公司的演讲费；并支持fering BV，默克和Goodlife出席会议。M.v.W.是Cochrane的高级编辑和《人类生殖更新》的主编。C.B.L.报告了来自奥根农（荷兰）的演讲者酬金，并在提交此手稿时担任《人类生殖》的主编。试验注册号berntr5423: ICTRP搜索门户（who.int）。
{"title":"Obstetric and perinatal outcomes from the follow-up of a multicentre randomized controlled trial investigating time-lapse embryo monitoring.","authors":"D C Kieslinger,C G Vergouw,F von Estorff,L Ramos,B Arends,M H J M Curfs,E Slappendel,E H Kostelijk,M H E C Pieters,D Consten,M O Verhoeven,D E Besselink,F Broekmans,B J Cohlen,J M J Smeenk,S Mastenbroek,C H de Koning,Y M van Kasteren,E Moll,J van Disseldorp,E A Brinkhuis,E A M Kuijper,W M van Baal,H G I van Weering,P J Q van der Linden,M H Gerards,P M Bossuyt,M van Wely,C B Lambalk","doi":"10.1093/humrep/deaf197","DOIUrl":"https://doi.org/10.1093/humrep/deaf197","url":null,"abstract":"STUDY QUESTIONDoes uninterrupted culture in a time-lapse incubator with or without a commercially available machine learning embryo selection algorithm result in comparable obstetric and perinatal outcomes as interrupted culture and morphological embryo selection?SUMMARY ANSWERThe application of uninterrupted culture in a time-lapse incubator with and without the use of an embryo selection algorithm is comparable to interrupted embryo culture and morphological embryo selection in terms of obstetric and perinatal results.WHAT IS KNOWN ALREADYThere is very limited evidence regarding the safety of time-lapse monitoring (TLM) from prospective randomized controlled trials (RCT). Recent RCTs have demonstrated that the application of TLM does not increase (cumulative) live birth rates or shorten the time to pregnancy within 1 year. Although most studies only report pregnancy rates, the safety of this commonly used method is also relevant for decision-making.STUDY DESIGN, SIZE, DURATIONThe obstetric and perinatal outcomes of patients scheduled for Day 3 single embryo transfer who participated in a multicentre RCT on TLM were studied (SelecTIMO trial). Three groups were compared: (i) TLE: embryo selection based on a commercially available Day 3 TLM algorithm, used adjunctively with morphology, and uninterrupted culture. (ii) TLR: routine morphological embryo selection and uninterrupted culture. (iii) CON: routine morphological embryo selection and interrupted culture.PARTICIPANTS/MATERIALS, SETTING, METHODSIn total, 1731 IVF/ICSI patients undergoing their first, second, or third oocyte retrieval cycle were randomized. Obstetric and perinatal data were registered for all pregnancies occurring after fresh and frozen embryo transfers associated with the initial oocyte retrieval cycle as well as natural conceptions within 1 year. Serious pregnancy complications and birth weight were considered main safety outcomes. Mean differences (MD) and age-adjusted relative risks (RRadj) and mean differences with 95% CI were calculated for TLE and TLR versus CON.MAIN RESULTS AND THE ROLE OF CHANCEA total of 827 women gave birth to a singleton during the follow-up period (TLE = 275, TLR = 278, CON = 274; P = 0.99). Of the 827 women who gave birth to a singleton, 497 deliveries originated from a fresh embryo transfer (60%), 294 from a frozen embryo transfer (36%), and 36 women conceived naturally (4%), with similar proportions in each study group. The proportion of women with serious pregnancy complications was comparable across the three groups (TLE vs CON: RRadj 0.95, 95% CI 0.65-1.40 and TLR vs CON: RRadj 1.03, 95% CI 0.70-1.50; P = 0.89). Mean (SD) gestational age at birth was 39.4 (1.9) weeks, 39.5 (1.5) weeks, and 39.3 (1.9) weeks, respectively. We found no evidence of differences in preterm and very preterm births between groups. Mean (SD) weight at birth was 3413 (588) g, 3412 (588) g, and 3377 (578) g, respectively (TLE vs CON: MD 34, 95% CI -62 to 129 and TLR vs ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"39 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370639","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 QUESTIONCan a universal diagnostic test (Karyomapping) be applied for preimplantation genetic testing for multiple monogenic disorders (PGT-M) and what is the misdiagnosis rate?SUMMARY ANSWERAmong 9020 cases of PGT-M, >1000 different disorders were diagnosed by Karyomapping; independent validation of >70% of cases did not detect a misdiagnosis.WHAT IS KNOWN ALREADYPGT-M, first performed in 1992, has been used for ∼40 000 clinical cases worldwide. A limiting factor in direct testing for disease mutations, however, is the need to design assays specific for each affected allele. Karyomapping, based on haplotype phasing using SNP microarrays, was developed in 2010 as a single, method tracing inheritance of any monogenic disorder. Karyomapping eliminates the impact of allele drop-out and DNA contamination on test accuracy and facilitates a short work-up time as the same assay platform is used for every case.STUDY DESIGN, SIZE, DURATIONHere, we used Karyomapping on a large PGT-M series from one diagnostic base from January 2014 to December 2021.PARTICIPANTS/MATERIALS, SETTING, METHODSThe 9020 individual Karyomapping cases were performed in three CooperSurgical genetic testing laboratories, in Livingston NJ, Michigan, or London (UK). All cases involved trophectoderm biopsy with embryo vitrification. DNA from cheek brush samples was obtained from both parents and an affected reference family member where possible. Genomic DNAs and that of whole genome amplified DNA from embryo biopsies were subjected to SNP microarray. Karyomapping was performed according to manufacturer's instructions by first importing into BlueFuse Multi software. Inheritance was determined as to where at-risk allele(s) were inherited, with 10 supporting 5' and 3' Key SNPs in a 2 Mbp flanking window. Wherever possible, direct mutation testing was performed using Sanger sequencing.MAIN RESULTS AND THE ROLE OF CHANCEA total of 1017 unique disorders were detected from mutations in 912 genes. Validation of 4120 mutations was possible in 73% of cases by direct sequencing, which confirmed that all diagnoses that could be assayed were accurate.LIMITATIONS, REASONS FOR CAUTIONKaryomapping can be limited by the availability of a reference, as well as parental genomic DNA, and some loci near the telomere may be more difficult to detect because of the limitations of the SNP array rather than the Karyomapping algorithm. Of the 27% of cases where we could not confirm the findings, we cannot comment on the misdiagnosis rate.WIDER IMPLICATIONS OF THE FINDINGSKaryomapping is now the single most used approach for PGT-M. As new approaches increasingly involve DNA sequencing, PGT for all genetic disease becomes possible by encapsulating the principles of Karyomapping and incorporating chromosome copy number analysis.TRIAL REGISTRATION NUMBERN/A.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by CooperSurgical. The PhD programs of A.S. and O.W. were supported by CooperSurgical (paid to
{"title":"Universal preimplantation genetic testing for monogenic disease (Karyomapping): diagnosis of >1000 unique disorders with no detected misdiagnoses.","authors":"Alessia Schadwell,Olivia Whiting,Leoni Xanthopoulou,Pere Colls,Evangelia Bakosi,N-Neka Goodall,Lia Ribustello,Peter Ellis,Tony Gordon,Darren K Griffin","doi":"10.1093/humrep/deaf198","DOIUrl":"https://doi.org/10.1093/humrep/deaf198","url":null,"abstract":"STUDY QUESTIONCan a universal diagnostic test (Karyomapping) be applied for preimplantation genetic testing for multiple monogenic disorders (PGT-M) and what is the misdiagnosis rate?SUMMARY ANSWERAmong 9020 cases of PGT-M, >1000 different disorders were diagnosed by Karyomapping; independent validation of >70% of cases did not detect a misdiagnosis.WHAT IS KNOWN ALREADYPGT-M, first performed in 1992, has been used for ∼40 000 clinical cases worldwide. A limiting factor in direct testing for disease mutations, however, is the need to design assays specific for each affected allele. Karyomapping, based on haplotype phasing using SNP microarrays, was developed in 2010 as a single, method tracing inheritance of any monogenic disorder. Karyomapping eliminates the impact of allele drop-out and DNA contamination on test accuracy and facilitates a short work-up time as the same assay platform is used for every case.STUDY DESIGN, SIZE, DURATIONHere, we used Karyomapping on a large PGT-M series from one diagnostic base from January 2014 to December 2021.PARTICIPANTS/MATERIALS, SETTING, METHODSThe 9020 individual Karyomapping cases were performed in three CooperSurgical genetic testing laboratories, in Livingston NJ, Michigan, or London (UK). All cases involved trophectoderm biopsy with embryo vitrification. DNA from cheek brush samples was obtained from both parents and an affected reference family member where possible. Genomic DNAs and that of whole genome amplified DNA from embryo biopsies were subjected to SNP microarray. Karyomapping was performed according to manufacturer's instructions by first importing into BlueFuse Multi software. Inheritance was determined as to where at-risk allele(s) were inherited, with 10 supporting 5' and 3' Key SNPs in a 2 Mbp flanking window. Wherever possible, direct mutation testing was performed using Sanger sequencing.MAIN RESULTS AND THE ROLE OF CHANCEA total of 1017 unique disorders were detected from mutations in 912 genes. Validation of 4120 mutations was possible in 73% of cases by direct sequencing, which confirmed that all diagnoses that could be assayed were accurate.LIMITATIONS, REASONS FOR CAUTIONKaryomapping can be limited by the availability of a reference, as well as parental genomic DNA, and some loci near the telomere may be more difficult to detect because of the limitations of the SNP array rather than the Karyomapping algorithm. Of the 27% of cases where we could not confirm the findings, we cannot comment on the misdiagnosis rate.WIDER IMPLICATIONS OF THE FINDINGSKaryomapping is now the single most used approach for PGT-M. As new approaches increasingly involve DNA sequencing, PGT for all genetic disease becomes possible by encapsulating the principles of Karyomapping and incorporating chromosome copy number analysis.TRIAL REGISTRATION NUMBERN/A.STUDY FUNDING/COMPETING INTEREST(S)This research was funded by CooperSurgical. The PhD programs of A.S. and O.W. were supported by CooperSurgical (paid to ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"148 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370728","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}
Roos Leroy, Jason Abbott, Nadia Benahmed, Cécile Camberlin, Mats De Jaeger, Dorthe Hartwell, Andrew Kent, Annemiek Nap, Cecilia Ng, Sien Ombelet, Karl-Werner Schweppe, Fabian Desimpel
STUDY QUESTION How is endometriosis care organized at the primary, secondary, and tertiary care levels in five high-income countries? SUMMARY ANSWER In all countries under study, initiatives have been taken to provide endometriosis care by experienced health care professionals in a multidisciplinary setting, but certification criteria for secondary and tertiary centres vary greatly across countries. WHAT IS KNOWN ALREADY Endometriosis is a highly prevalent and complex disease with potentially significant physical, sexual, psychological, social, and economic impacts on those affected. Logically, a multidisciplinary approach by health care providers with expertise and experience has been recommended. STUDY DESIGN, SIZE, DURATION This study included five high-income countries where endometriosis care was centralized to some extent or where a national action plan for endometriosis was developed. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on a review of the literature, five countries were selected: Australia, Denmark, Germany, the Netherlands, and the UK. Information was collected through a review of peer-reviewed and grey literature that was revised and amended by experts from each country. MAIN RESULTS AND THE ROLE OF CHANCE In 2018, Australia launched a comprehensive government-led national action plan for endometriosis. In Germany, secondary and tertiary endometriosis care is organized at three levels, while in Denmark and the Netherlands, a two-level system has been installed, whereas in the UK, only tertiary referral centres have been initiated to date. Only in Denmark must secondary care centres refer patients with advanced endometriosis to tertiary care centres. In all countries studied, treatment for advanced endometriosis is also carried out in centres without certification, where the quality of care is not assessed. National endometriosis registries have commenced and are active in Australia and the UK. In the selected countries, various initiatives have been taken to enhance the training of health care professionals, to inform patients, and to increase awareness on endometriosis. In none of the studied countries is endometriosis (automatically) recognized and/or registered as a chronic condition. LIMITATIONS, REASONS FOR CAUTION In the five countries evaluated, there are continuing efforts to further improve the organization of endometriosis care. With ongoing revisions of service provision, resourcing and health care structures for endometriosis are evolving considerably; therefore, this overview should be considered as a snapshot taken up to early 2025. Since this overview relies principally on scientific literature, policy documents, and expert opinions, and not on objective outcomes, there may be dyssynchrony between what is summarized here and actual clinical practice. WIDER IMPLICATIONS OF THE FINDINGS This overview may provide advice and guidance for policy makers in the development of a framework for the organization of endomet
{"title":"Comparative analysis of the organization of endometriosis care in five high-income countries: implications for health systems and policy","authors":"Roos Leroy, Jason Abbott, Nadia Benahmed, Cécile Camberlin, Mats De Jaeger, Dorthe Hartwell, Andrew Kent, Annemiek Nap, Cecilia Ng, Sien Ombelet, Karl-Werner Schweppe, Fabian Desimpel","doi":"10.1093/humrep/deaf190","DOIUrl":"https://doi.org/10.1093/humrep/deaf190","url":null,"abstract":"STUDY QUESTION How is endometriosis care organized at the primary, secondary, and tertiary care levels in five high-income countries? SUMMARY ANSWER In all countries under study, initiatives have been taken to provide endometriosis care by experienced health care professionals in a multidisciplinary setting, but certification criteria for secondary and tertiary centres vary greatly across countries. WHAT IS KNOWN ALREADY Endometriosis is a highly prevalent and complex disease with potentially significant physical, sexual, psychological, social, and economic impacts on those affected. Logically, a multidisciplinary approach by health care providers with expertise and experience has been recommended. STUDY DESIGN, SIZE, DURATION This study included five high-income countries where endometriosis care was centralized to some extent or where a national action plan for endometriosis was developed. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on a review of the literature, five countries were selected: Australia, Denmark, Germany, the Netherlands, and the UK. Information was collected through a review of peer-reviewed and grey literature that was revised and amended by experts from each country. MAIN RESULTS AND THE ROLE OF CHANCE In 2018, Australia launched a comprehensive government-led national action plan for endometriosis. In Germany, secondary and tertiary endometriosis care is organized at three levels, while in Denmark and the Netherlands, a two-level system has been installed, whereas in the UK, only tertiary referral centres have been initiated to date. Only in Denmark must secondary care centres refer patients with advanced endometriosis to tertiary care centres. In all countries studied, treatment for advanced endometriosis is also carried out in centres without certification, where the quality of care is not assessed. National endometriosis registries have commenced and are active in Australia and the UK. In the selected countries, various initiatives have been taken to enhance the training of health care professionals, to inform patients, and to increase awareness on endometriosis. In none of the studied countries is endometriosis (automatically) recognized and/or registered as a chronic condition. LIMITATIONS, REASONS FOR CAUTION In the five countries evaluated, there are continuing efforts to further improve the organization of endometriosis care. With ongoing revisions of service provision, resourcing and health care structures for endometriosis are evolving considerably; therefore, this overview should be considered as a snapshot taken up to early 2025. Since this overview relies principally on scientific literature, policy documents, and expert opinions, and not on objective outcomes, there may be dyssynchrony between what is summarized here and actual clinical practice. WIDER IMPLICATIONS OF THE FINDINGS This overview may provide advice and guidance for policy makers in the development of a framework for the organization of endomet","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"19 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295860","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}
K Yoshida,S Kimura,M Taguchi,H Morimoto,M Kanatsu-Shinohara,T Shinohara,Y Obata
STUDY QUESTIONCan in vitro systems, combined with transient gene expression or factor supplementation, completely restore fertility in congenitally infertile mice?SUMMARY ANSWERTransient expression of Kitl via adeno-associated virus (AAV) vectors or supplementation with recombinant KITL in KitlSl-t/KitlSl-t mice-a model of congenital infertility caused by a mutation in the Kitl locus-resulted in the production of mature oocytes and the birth of healthy, fertile offspring.WHAT IS KNOWN ALREADYAlthough in vivo gene delivery has enabled offspring production in infertile mouse models, low efficiency, unpredictability of parturition timing, inflammatory risk, possible viral genome integration, and lack of real-time oogenesis observation remain major concerns. Despite the potential of in vitro oogenesis as an alternative, complete functional restoration of gene deficiency has not been reported.STUDY DESIGN, SIZE, DURATIONAAV-mCherry was applied to wild-type mouse ovaries, and expression levels were compared across 15 serotypes (2.5 × 1011 viral genomes/ml; N = 4-12; 4-day infection, 20-day culture) to identify optimal AAV serotypes for ovarian gene delivery. The effects of AAV-Kitl infection (six doses; N = 3-5) and recombinant KITL supplementation (four doses; N = 5) on oocyte growth were evaluated in KitlSl-t/KitlSl-t mouse ovaries. On culture day 17 or 18, secondary follicles were isolated and cultured for an additional 16 days to evaluate oocyte competence for maturation, fertilization, and full-term development. Offspring were delivered 52-53 days after treatment initiation.PARTICIPANTS/MATERIALS, SETTING, METHODSOvaries from KitlSl-t/KitlSl-t mice were dissociated into single cells and reaggregated in U-bottom wells with media containing AAV8-Kitl, AAV9-Kitl, or recombinant KITL. Reconstituted ovaries were cultured on insert membranes, thereby allowing primordial follicles to develop into secondary follicles. Isolated secondary follicles were further cultured to the antral stage, and cumulus-oocyte complexes were subjected to IVM and IVF. The resulting embryos were transferred to foster mothers. Finally, the offspring were subjected to PCR screening for AAV sequences and fertility tests.MAIN RESULTS AND THE ROLE OF CHANCEAAV8, AAV9, AAVrh.10, and AAVrh.32.33 induced significantly higher levels of mCherry expression in wild-type mouse ovaries than 10 of the 15 AAV evaluated serotypes in vitro (P < 0.05). AAV8-Kitl promoted primordial follicle activation in a dose-dependent manner in KitlSl-t/KitlSl-t mouse ovaries, with the highest number of secondary follicles (80 per reconstituted ovary) obtained at 1.0 × 1011 vg/ml (P < 0.05). In contrast, AAV9-Kitl required 2.5- to 10-fold higher titers to achieve comparable levels of secondary follicle formation. Contrastingly, no secondary follicles were formed in KitlSl-t/KitlSl-t mouse ovaries following mock treatment. Furthermore, supplementation with 200 ng/ml recombinant KITL supported secondary follicl
{"title":"In vitro system completely restores oogenesis in congenitally infertile mice.","authors":"K Yoshida,S Kimura,M Taguchi,H Morimoto,M Kanatsu-Shinohara,T Shinohara,Y Obata","doi":"10.1093/humrep/deaf194","DOIUrl":"https://doi.org/10.1093/humrep/deaf194","url":null,"abstract":"STUDY QUESTIONCan in vitro systems, combined with transient gene expression or factor supplementation, completely restore fertility in congenitally infertile mice?SUMMARY ANSWERTransient expression of Kitl via adeno-associated virus (AAV) vectors or supplementation with recombinant KITL in KitlSl-t/KitlSl-t mice-a model of congenital infertility caused by a mutation in the Kitl locus-resulted in the production of mature oocytes and the birth of healthy, fertile offspring.WHAT IS KNOWN ALREADYAlthough in vivo gene delivery has enabled offspring production in infertile mouse models, low efficiency, unpredictability of parturition timing, inflammatory risk, possible viral genome integration, and lack of real-time oogenesis observation remain major concerns. Despite the potential of in vitro oogenesis as an alternative, complete functional restoration of gene deficiency has not been reported.STUDY DESIGN, SIZE, DURATIONAAV-mCherry was applied to wild-type mouse ovaries, and expression levels were compared across 15 serotypes (2.5 × 1011 viral genomes/ml; N = 4-12; 4-day infection, 20-day culture) to identify optimal AAV serotypes for ovarian gene delivery. The effects of AAV-Kitl infection (six doses; N = 3-5) and recombinant KITL supplementation (four doses; N = 5) on oocyte growth were evaluated in KitlSl-t/KitlSl-t mouse ovaries. On culture day 17 or 18, secondary follicles were isolated and cultured for an additional 16 days to evaluate oocyte competence for maturation, fertilization, and full-term development. Offspring were delivered 52-53 days after treatment initiation.PARTICIPANTS/MATERIALS, SETTING, METHODSOvaries from KitlSl-t/KitlSl-t mice were dissociated into single cells and reaggregated in U-bottom wells with media containing AAV8-Kitl, AAV9-Kitl, or recombinant KITL. Reconstituted ovaries were cultured on insert membranes, thereby allowing primordial follicles to develop into secondary follicles. Isolated secondary follicles were further cultured to the antral stage, and cumulus-oocyte complexes were subjected to IVM and IVF. The resulting embryos were transferred to foster mothers. Finally, the offspring were subjected to PCR screening for AAV sequences and fertility tests.MAIN RESULTS AND THE ROLE OF CHANCEAAV8, AAV9, AAVrh.10, and AAVrh.32.33 induced significantly higher levels of mCherry expression in wild-type mouse ovaries than 10 of the 15 AAV evaluated serotypes in vitro (P < 0.05). AAV8-Kitl promoted primordial follicle activation in a dose-dependent manner in KitlSl-t/KitlSl-t mouse ovaries, with the highest number of secondary follicles (80 per reconstituted ovary) obtained at 1.0 × 1011 vg/ml (P < 0.05). In contrast, AAV9-Kitl required 2.5- to 10-fold higher titers to achieve comparable levels of secondary follicle formation. Contrastingly, no secondary follicles were formed in KitlSl-t/KitlSl-t mouse ovaries following mock treatment. Furthermore, supplementation with 200 ng/ml recombinant KITL supported secondary follicl","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"56 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241102","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}
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