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}
A P van Haaps,A M F Schreurs,K Rosielle,V Mijatovic,J W Kallewaard,K Dreyer
STUDY QUESTIONWhat is the effect of Virtual Reality (VR) on anxiety and pain during oocyte retrieval in IVF/ICSI treatment?SUMMARY ANSWERThere is no significant effect of VR on anxiety and pain during oocyte retrieval in IVF/ICSI treatment.WHAT IS KNOWN ALREADYPatients undergoing oocyte retrieval in IVF/ICSI treatment often experience anxiety and pain, despite conscious sedation. VR might offer a solution since it has been successful in reducing procedural anxiety and pain during medical procedures, with the potential to replace standard analgesic care.STUDY DESIGN, SIZE, DURATIONA single-centre, open-label, randomized controlled trial was conducted between February 2023 and August 2024. Due to the nature of the intervention, the study was not blinded.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients undergoing oocyte retrieval as part of IVF/ICSI treatment were screened. After providing informed consent, participants were randomized between oocyte retrieval with VR added to conscious sedation and oocyte retrieval with conscious sedation only. When assigned to the intervention group, patients received the VR intervention through a head-mounted device, showing nature films and relaxation exercises. This was added to standard care which includes analgesia and sedatives. Sounds were delivered through the head-mounted device or headphones. The primary outcome was pre- and post-procedural anxiety, measured using the STAI questionnaire. Secondary outcomes included procedural pain (NRS, scale 0-10), satisfaction scores (NRS, scale 0-10), VR preferences, and side effects.MAIN RESULTS AND THE ROLE OF CHANCEThere were 113 participants included: 57 in the intervention group receiving VR and 56 in the control group not receiving VR. We observed no differences between the intervention and control groups in pre-procedural anxiety (mean difference (MD) 0.14 (95% CI -1.78, 2.05), P = 0.885), post-procedural anxiety (MD 0.45 (95% CI -1.21, 2.11), P = 0.589), overall pain (MD -0.12 (95% CI -0.97, 0.73), P = 0.779), and peak pain (MD 0.59 (-0.51, 1.68), P = 0.287).LIMITATIONS, REASONS FOR CAUTIONVR might only be effective for a certain group of patients undergoing retrieval, or might be more effective in reducing pre-procedural anxiety, which in turn might lead to a reduction in procedural pain. Furthermore, it might reduce pain up to a certain threshold, or be effective when the duration of the procedure is short.WIDER IMPLICATIONS OF THE FINDINGSSince VR does not affect anxiety and pain for the general patient population undergoing oocyte retrieval, we do not advise incorporating VR to standard IVF/ICSI anxiety and pain management. For future studies, it is important to investigate which subgroup could benefit from VR and how it could be implemented to study interventions from a non-pharmacological approach. Patient preferences regarding anxiety and pain management during IVF/ICSI treatment should be considered.STUDY FUNDING/COMPETING INTEREST(S)External funding f
研究问题：在IVF/ICSI治疗中，虚拟现实（VR）对卵母细胞提取过程中的焦虑和疼痛有什么影响？结论：在IVF/ICSI治疗中，VR对取卵过程中的焦虑和疼痛无显著影响。已知情况：在体外受精/ICSI治疗中接受卵母细胞提取的患者，尽管有清醒的镇静，但通常会感到焦虑和疼痛。虚拟现实可能会提供一个解决方案，因为它已经成功地减少了医疗过程中的程序焦虑和疼痛，有可能取代标准的镇痛治疗。研究设计、规模、持续时间一项单中心、开放标签、随机对照试验于2023年2月至2024年8月进行。由于干预的性质，该研究没有采用盲法。参与者/材料，环境，方法接受卵母细胞回收作为IVF/ICSI治疗的一部分的患者进行筛选。在提供知情同意后，参与者被随机分为两组，一组是在有意识镇静的情况下使用VR取回卵母细胞，另一组是只使用有意识镇静取回卵母细胞。当被分配到干预组时，患者通过头戴式设备接受VR干预，播放自然电影和放松练习。这是添加到标准护理，包括镇痛和镇静剂。声音通过头戴式设备或耳机传递。主要结果是手术前和手术后的焦虑，使用STAI问卷进行测量。次要结局包括程序性疼痛（NRS，量表0-10）、满意度评分（NRS，量表0-10）、VR偏好和副作用。主要结果和机会的作用纳入113名参与者：57名干预组接受虚拟现实，56名对照组未接受虚拟现实。我们观察到干预组和对照组在手术前焦虑（平均差异（MD） 0.14 (95% CI -1.78, 2.05), P = 0.885），手术后焦虑（MD 0.45 (95% CI -1.21, 2.11), P = 0.589），总体疼痛（MD -0.12 (95% CI -0.97, 0.73), P = 0.779）和峰值疼痛（MD 0.59 (-0.51, 1.68), P = 0.287）方面没有差异。局限性：注意的原因：vr可能只对某一组接受取出术的患者有效，或者可能在减少手术前焦虑方面更有效，这反过来可能导致手术疼痛的减少。此外，它可以将疼痛减轻到一定程度，或者在手术持续时间短的情况下有效。由于VR不会影响接受卵母细胞提取的一般患者群体的焦虑和疼痛，我们不建议将VR纳入标准的IVF/ICSI焦虑和疼痛管理。对于未来的研究，重要的是调查哪个亚组可以从VR中受益，以及如何通过非药物方法实施研究干预措施。应考虑试管婴儿/ICSI治疗期间患者对焦虑和疼痛管理的偏好。研究资金/竞争利益(S)本研究已收到来自ZonMw的外部资金（资助号838002978）、实施和扩大培训以及Theramex的Eggcelent Change赠款，用于支付VR设备的费用。据报道，A.P.v.H.和K.R.已获得默克公司的旅行资助，前往ESHRE 2022。据报道，A.M.F.S.曾受邀在ESHRE发表演讲，ESHRE的差旅和酒店费用由该机构承担。据报道，V.M.已经获得了来自Guerbet， Merck和ferling的机构研究资助。他从格贝特那里获得了旅费和演讲费。J.W.K.是波士顿科学公司、Saluda、negro、Abbott和Medtronic公司的顾问委员会成员，并从这些组织获得咨询费。他是BNS的董事会成员。据报道，KD已经获得了来自Guerbet的机构研究资助，来自Guerbet的演讲费，以及参加默克和Guerbet会议的财政支持。试验注册号05555498。试验注册日期为2022年9月26日。第一个患者入组日期2023年2月7日。
{"title":"No anxiety or pain reduction by Virtual Reality during oocyte retrieval in IVF/ICSI treatment: results of a randomized controlled trial.","authors":"A P van Haaps,A M F Schreurs,K Rosielle,V Mijatovic,J W Kallewaard,K Dreyer","doi":"10.1093/humrep/deaf193","DOIUrl":"https://doi.org/10.1093/humrep/deaf193","url":null,"abstract":"STUDY QUESTIONWhat is the effect of Virtual Reality (VR) on anxiety and pain during oocyte retrieval in IVF/ICSI treatment?SUMMARY ANSWERThere is no significant effect of VR on anxiety and pain during oocyte retrieval in IVF/ICSI treatment.WHAT IS KNOWN ALREADYPatients undergoing oocyte retrieval in IVF/ICSI treatment often experience anxiety and pain, despite conscious sedation. VR might offer a solution since it has been successful in reducing procedural anxiety and pain during medical procedures, with the potential to replace standard analgesic care.STUDY DESIGN, SIZE, DURATIONA single-centre, open-label, randomized controlled trial was conducted between February 2023 and August 2024. Due to the nature of the intervention, the study was not blinded.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients undergoing oocyte retrieval as part of IVF/ICSI treatment were screened. After providing informed consent, participants were randomized between oocyte retrieval with VR added to conscious sedation and oocyte retrieval with conscious sedation only. When assigned to the intervention group, patients received the VR intervention through a head-mounted device, showing nature films and relaxation exercises. This was added to standard care which includes analgesia and sedatives. Sounds were delivered through the head-mounted device or headphones. The primary outcome was pre- and post-procedural anxiety, measured using the STAI questionnaire. Secondary outcomes included procedural pain (NRS, scale 0-10), satisfaction scores (NRS, scale 0-10), VR preferences, and side effects.MAIN RESULTS AND THE ROLE OF CHANCEThere were 113 participants included: 57 in the intervention group receiving VR and 56 in the control group not receiving VR. We observed no differences between the intervention and control groups in pre-procedural anxiety (mean difference (MD) 0.14 (95% CI -1.78, 2.05), P = 0.885), post-procedural anxiety (MD 0.45 (95% CI -1.21, 2.11), P = 0.589), overall pain (MD -0.12 (95% CI -0.97, 0.73), P = 0.779), and peak pain (MD 0.59 (-0.51, 1.68), P = 0.287).LIMITATIONS, REASONS FOR CAUTIONVR might only be effective for a certain group of patients undergoing retrieval, or might be more effective in reducing pre-procedural anxiety, which in turn might lead to a reduction in procedural pain. Furthermore, it might reduce pain up to a certain threshold, or be effective when the duration of the procedure is short.WIDER IMPLICATIONS OF THE FINDINGSSince VR does not affect anxiety and pain for the general patient population undergoing oocyte retrieval, we do not advise incorporating VR to standard IVF/ICSI anxiety and pain management. For future studies, it is important to investigate which subgroup could benefit from VR and how it could be implemented to study interventions from a non-pharmacological approach. Patient preferences regarding anxiety and pain management during IVF/ICSI treatment should be considered.STUDY FUNDING/COMPETING INTEREST(S)External funding f","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"107 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241105","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}
Repon C Paul,Rebecca Deans,Amanda Henry,Cecilia Ng,Ingrid Rowlands,Gita D Mishra,Jason Abbott,Georgina M Chambers
STUDY QUESTIONHow do cumulative live birth rates (CLBRs) in women with endometriosis compare to those with other infertility diagnoses undergoing ART?SUMMARY ANSWERWomen with endometriosis as the sole cause of infertility achieved higher CLBRs compared to those with additional infertility diagnoses (endometriosis-plus) or other non-endometriosis causes of infertility.WHAT IS KNOWN ALREADYEndometriosis affects approximately 10% of women of reproductive age and is a major cause of infertility, with many women resorting to ART treatments in the hope of achieving a pregnancy. However, the comparative success rates of ART for these women, compared to those with other causes of infertility is not well understood.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study included 79 318 women who initiated autologous ART between 2014 and 2019 in Australia and New Zealand, with follow-up through 2021 or the first live birth.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were categorized into three groups based on infertility diagnosis: endometriosis-only (n = 4311), endometriosis-plus (n = 6312; endometriosis with other infertility factors) and other-infertility (n = 68 695; no endometriosis). Conservative and optimal CLBRs were calculated based on assumptions made about the chance of live birth for women who discontinued treatment.MAIN RESULTS AND THE ROLE OF CHANCEEndometriosis was reported as the sole cause of infertility in 5% of women (endometriosis-only), while 8% had endometriosis with other diagnoses (endometriosis-plus). The remaining women had either other causes of infertility (63%) or unexplained infertility (24%). Depending on assumptions made regarding patients who discontinued treatment, the CLBR by the sixth complete cycle for women diagnosed with endometriosis-only ranged from 64% to 83%; for women with an endometriosis-plus diagnoses, the CLBR ranged from 54.3% to 68.7%; and for women without endometriosis, the CLBR ranged from 57.3% to 76.5%. Compared to women without endometriosis, the live birth rate was 6% higher in endometriosis-only group (RR: 1.06; 95% CI: 1.04-1.08) and 5% lower in endometriosis-plus group (RR: 0.95; 95% CI: 0.93-0.97). Compared to the endometriosis-only group, pregnancy loss was 46% higher (RR: 1.46; 95% CI: 1.35-1.59) in endometriosis-plus group.LIMITATIONS, REASONS FOR CAUTIONThe study did not assess endometriosis severity or phenotype, which may influence ART outcomes.WIDER IMPLICATIONS OF THE FINDINGSThese findings provide critical data for counselling women with endometriosis regarding ART success. The higher CLBR in the endometriosis-only group suggests that isolated endometriosis does not negatively impact ART outcomes and highlights the need for tailored management in women with additional infertility factors.STUDY FUNDING/COMPETING INTEREST(S)This study is funded through the Medical Research Future Fund (MRFF) Research Data Infrastructure grant (MRFRFD000065). The sponsors had no role in the des
{"title":"Cumulative live birth rates in women with endometriosis undergoing ART treatment.","authors":"Repon C Paul,Rebecca Deans,Amanda Henry,Cecilia Ng,Ingrid Rowlands,Gita D Mishra,Jason Abbott,Georgina M Chambers","doi":"10.1093/humrep/deaf191","DOIUrl":"https://doi.org/10.1093/humrep/deaf191","url":null,"abstract":"STUDY QUESTIONHow do cumulative live birth rates (CLBRs) in women with endometriosis compare to those with other infertility diagnoses undergoing ART?SUMMARY ANSWERWomen with endometriosis as the sole cause of infertility achieved higher CLBRs compared to those with additional infertility diagnoses (endometriosis-plus) or other non-endometriosis causes of infertility.WHAT IS KNOWN ALREADYEndometriosis affects approximately 10% of women of reproductive age and is a major cause of infertility, with many women resorting to ART treatments in the hope of achieving a pregnancy. However, the comparative success rates of ART for these women, compared to those with other causes of infertility is not well understood.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study included 79 318 women who initiated autologous ART between 2014 and 2019 in Australia and New Zealand, with follow-up through 2021 or the first live birth.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were categorized into three groups based on infertility diagnosis: endometriosis-only (n = 4311), endometriosis-plus (n = 6312; endometriosis with other infertility factors) and other-infertility (n = 68 695; no endometriosis). Conservative and optimal CLBRs were calculated based on assumptions made about the chance of live birth for women who discontinued treatment.MAIN RESULTS AND THE ROLE OF CHANCEEndometriosis was reported as the sole cause of infertility in 5% of women (endometriosis-only), while 8% had endometriosis with other diagnoses (endometriosis-plus). The remaining women had either other causes of infertility (63%) or unexplained infertility (24%). Depending on assumptions made regarding patients who discontinued treatment, the CLBR by the sixth complete cycle for women diagnosed with endometriosis-only ranged from 64% to 83%; for women with an endometriosis-plus diagnoses, the CLBR ranged from 54.3% to 68.7%; and for women without endometriosis, the CLBR ranged from 57.3% to 76.5%. Compared to women without endometriosis, the live birth rate was 6% higher in endometriosis-only group (RR: 1.06; 95% CI: 1.04-1.08) and 5% lower in endometriosis-plus group (RR: 0.95; 95% CI: 0.93-0.97). Compared to the endometriosis-only group, pregnancy loss was 46% higher (RR: 1.46; 95% CI: 1.35-1.59) in endometriosis-plus group.LIMITATIONS, REASONS FOR CAUTIONThe study did not assess endometriosis severity or phenotype, which may influence ART outcomes.WIDER IMPLICATIONS OF THE FINDINGSThese findings provide critical data for counselling women with endometriosis regarding ART success. The higher CLBR in the endometriosis-only group suggests that isolated endometriosis does not negatively impact ART outcomes and highlights the need for tailored management in women with additional infertility factors.STUDY FUNDING/COMPETING INTEREST(S)This study is funded through the Medical Research Future Fund (MRFF) Research Data Infrastructure grant (MRFRFD000065). The sponsors had no role in the des","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"53 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235551","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}
Anna Mathilde Yde, Lotte Berdiin Colmorn, Anja Pinborg, Lone Schmidt, Niels Kroman, Frederik Nikolaj Kyhl, Ditte Vassard, Kirsten Tryde Macklon
STUDY QUESTION Does livebirth probability differ between women diagnosed with breast cancer and unaffected women and is it impacted by age at diagnosis, time trends, parity, partnership status, and the presence of lymph node metastases and distant metastases? SUMMARY ANSWER Livebirth probability was significantly reduced in 5940 women diagnosed with breast cancer aged 18–40 years during 1968–2016 compared to 1 126 478 age-matched unaffected women, particularly among women with higher diagnosis age, parity ≥ 1, marriage, and the presence of nodal involvement and distant metastases. WHAT IS KNOWN ALREADY The survival rate for women diagnosed with breast cancer has increased over the recent decades, and in Denmark, the 5-year survival rate for women diagnosed <50 years of age was 92.2% in 2022. Chemotherapy can damage the ovarian reserve, resulting in premature ovarian insufficiency and infertility. The age of first-time mothers is increasing, and many women have not yet completed family building at the time of diagnosis. Consequently, greater focus is now placed on quality-of-life following breast cancer, including the possibility of survivors to have children. Studies have shown a decreased fertility rate in women diagnosed with cancer during their reproductive lifespan, however, studies specifically focusing on the probability of livebirth in women previously diagnosed with breast cancer are scarce. STUDY DESIGN, SIZE, DURATION This is a national, register-based cohort study including women diagnosed with breast cancer from the Danish Cancer Register between 1968 and 2016, aged 18–40 years at time of diagnosis (n = 5940). Each woman was randomly matched with ∼190 unaffected women from the background population according to the age at diagnosis (n = 1 126 478). The women were followed in medical and sociodemographic national population registers until childbirth, death, immigration, or end of study (31 December 2018). PARTICIPANTS/MATERIALS, SETTING, METHODS In all analyses, we compared the probability of livebirth between women diagnosed with breast cancer and the age-matched comparison group. Analyses were stratified by parity- and partnership status at diagnosis, age-group at diagnosis, and year of diagnosis. Stratified analyses on the probability of livebirth were conducted for women with lymph-node metastases and distant metastases at the time of diagnosis. Analyses were adjusted for age, year of diagnosis, parity, educational level, and migration status. MAIN RESULTS AND THE ROLE OF CHANCE The study population consisted of 5940 women aged 18–40 years at diagnosis of breast cancer between 1968 and 2016 and 1 126 478 women in the age-matched comparison group. Breast cancer survivors had a significantly lower probability of livebirth than the age-matched comparison group (aHR 0.38 [95% CI 0.35–0.41]); negatively impacted by increasing age at diagnosis (35–40 years: aHR 0.34 [95% CI 0.28–0.40], 18–24 years: 0.66 [95% CI 0.46–0.95]), parit
研究问题：诊断为乳腺癌的妇女和未患乳腺癌的妇女的活产概率是否不同？它是否受到诊断年龄、时间趋势、胎次、伴侣状态、淋巴结转移和远处转移的存在的影响？1968年至2016年期间，5940名18-40岁乳腺癌确诊女性的活产概率显著低于1 126 478名年龄匹配的未受影响女性，特别是在诊断年龄较高、胎次≥1、已婚、存在淋巴结累及远处转移的女性中。近几十年来，被诊断为乳腺癌的女性的存活率有所增加，在丹麦，被诊断为乳腺癌的女性的5年生存率为。2022年，50岁以上人口占92.2%。化疗会损害卵巢储备，导致卵巢功能不全和不孕。第一次做母亲的年龄正在增加，许多妇女在诊断时尚未完成家庭建设。因此，现在更加注重乳腺癌后的生活质量，包括幸存者生育的可能性。研究表明，被诊断患有癌症的妇女在其生殖寿命期间的生育率下降，然而，专门关注先前被诊断患有乳腺癌的妇女活产概率的研究很少。研究设计、规模、持续时间这是一项全国性、基于登记的队列研究，纳入了1968年至2016年丹麦癌症登记中诊断为乳腺癌的女性，诊断时年龄为18-40岁（n = 5940）。根据诊断时的年龄，每名妇女与背景人群中约190名未受影响的妇女随机配对（n = 1 126 478）。在医学和社会人口学国家人口登记册中对这些妇女进行跟踪，直到分娩、死亡、移民或研究结束（2018年12月31日）。参与者/材料、环境、方法在所有的分析中，我们比较了诊断为乳腺癌的妇女和年龄匹配的对照组之间的活产概率。分析按诊断时的胎次和伴侣关系状况、诊断时的年龄组和诊断年份进行分层。对诊断时淋巴结转移和远处转移的妇女进行了活产概率的分层分析。分析调整了年龄、诊断年份、平价、教育水平和移民状况。研究人群包括1968年至2016年期间诊断为乳腺癌的5940名年龄在18-40岁的女性和年龄匹配的对照组的126478名女性。乳腺癌幸存者的活产概率明显低于年龄匹配的对照组（aHR 0.38 [95% CI 0.35-0.41]）；增加诊断年龄（35-40岁：aHR 0.34 [95% CI 0.28-0.40]， 18-24岁：0.66 [95% CI 0.46-0.95]）、胎次≥1（已产：aHR 0.31 [95% CI 0.27-0.35]，未产：0.51 [95% CI 0.45-0.59]）和婚姻（已婚：aHR 0.31 [95% CI 0.27-0.36]，单身0.53 [95% CI 0.45-0.63]）均有负面影响。近几十年来被诊断为乳腺癌增加了未生育妇女活产的可能性；然而，在生育妇女中没有发现同样的联系。在淋巴结受累（48%）和远处转移（3%）的女性中，与未受影响的女性相比，活产的概率分别为aHR 0.30 [95% CI 0.26-0.35]和0.18 [95% CI 0.08-0.42]。局限性和谨慎的原因我们没有关于妇女是否想要孩子或她们是否在接受促性腺毒素治疗前接受了生育保留（FP）的信息。对于最近几十年确诊的女性，随访时间有限。关于他莫昔芬治疗雌激素受体阳性肿瘤的信息可能是相关的，因为它可能会延迟妊娠，从而降低受孕几率。研究结果的更广泛意义我们的研究结果强调了肿瘤生育咨询和计划生育对诊断为乳腺癌的年轻女性的持续重要性，特别是在诊断接近生育期的女性以及存在淋巴结转移和远处转移的女性中。研究经费/竞争利益(S)本研究由丹麦独立研究基金（资助号10.46540/4308-00130B）资助。Anja Pinborg获得了Gedeon Richter、Ferring Pharmaceuticals、Merck A/S和Cryos的资助（支付给机构）和咨询费；Gedeon Richter、Ferring Pharmaceuticals、Merck A/S和Organon的酬金；并支持出席会议和/或旅行（支付给机构）由吉迪恩·里希特。这些公司没有参与这项研究。其余作者无利益冲突需要申报。试验注册号n / a。
{"title":"Livebirth among 5940 Danish women diagnosed with breast cancer at age 18–40 years between 1968 and 2016: a register-based cohort study","authors":"Anna Mathilde Yde, Lotte Berdiin Colmorn, Anja Pinborg, Lone Schmidt, Niels Kroman, Frederik Nikolaj Kyhl, Ditte Vassard, Kirsten Tryde Macklon","doi":"10.1093/humrep/deaf192","DOIUrl":"https://doi.org/10.1093/humrep/deaf192","url":null,"abstract":"STUDY QUESTION Does livebirth probability differ between women diagnosed with breast cancer and unaffected women and is it impacted by age at diagnosis, time trends, parity, partnership status, and the presence of lymph node metastases and distant metastases? SUMMARY ANSWER Livebirth probability was significantly reduced in 5940 women diagnosed with breast cancer aged 18–40 years during 1968–2016 compared to 1 126 478 age-matched unaffected women, particularly among women with higher diagnosis age, parity ≥ 1, marriage, and the presence of nodal involvement and distant metastases. WHAT IS KNOWN ALREADY The survival rate for women diagnosed with breast cancer has increased over the recent decades, and in Denmark, the 5-year survival rate for women diagnosed &lt;50 years of age was 92.2% in 2022. Chemotherapy can damage the ovarian reserve, resulting in premature ovarian insufficiency and infertility. The age of first-time mothers is increasing, and many women have not yet completed family building at the time of diagnosis. Consequently, greater focus is now placed on quality-of-life following breast cancer, including the possibility of survivors to have children. Studies have shown a decreased fertility rate in women diagnosed with cancer during their reproductive lifespan, however, studies specifically focusing on the probability of livebirth in women previously diagnosed with breast cancer are scarce. STUDY DESIGN, SIZE, DURATION This is a national, register-based cohort study including women diagnosed with breast cancer from the Danish Cancer Register between 1968 and 2016, aged 18–40 years at time of diagnosis (n = 5940). Each woman was randomly matched with ∼190 unaffected women from the background population according to the age at diagnosis (n = 1 126 478). The women were followed in medical and sociodemographic national population registers until childbirth, death, immigration, or end of study (31 December 2018). PARTICIPANTS/MATERIALS, SETTING, METHODS In all analyses, we compared the probability of livebirth between women diagnosed with breast cancer and the age-matched comparison group. Analyses were stratified by parity- and partnership status at diagnosis, age-group at diagnosis, and year of diagnosis. Stratified analyses on the probability of livebirth were conducted for women with lymph-node metastases and distant metastases at the time of diagnosis. Analyses were adjusted for age, year of diagnosis, parity, educational level, and migration status. MAIN RESULTS AND THE ROLE OF CHANCE The study population consisted of 5940 women aged 18–40 years at diagnosis of breast cancer between 1968 and 2016 and 1 126 478 women in the age-matched comparison group. Breast cancer survivors had a significantly lower probability of livebirth than the age-matched comparison group (aHR 0.38 [95% CI 0.35–0.41]); negatively impacted by increasing age at diagnosis (35–40 years: aHR 0.34 [95% CI 0.28–0.40], 18–24 years: 0.66 [95% CI 0.46–0.95]), parit","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"78 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203258","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}
Elaine de Quadros, Jia Xu, Nathan Treff, Diego Marin, Arielle Freedman, Cristian Milevski, Kathleen Miller, Minglei Bian
<p><strong>Study question: </strong>Are segmental aneuploidies identified in human embryos more likely to occur within known fragile sites of the genome?</p><p><strong>Summary answer: </strong>Segmental breaks in the autosomes of human preimplantation embryos occur more frequently in known fragile areas of the genome.</p><p><strong>What is known already: </strong>Fragile sites represent specific loci in the genome characterized by inhibition of DNA synthesis when exposed to known inhibitors and are particularly sensitive to replication stress and instability.</p><p><strong>Study design, size, duration: </strong>This was a retrospective analysis of single nucleotide polymorphism (SNP) array-based preimplantation genetic testing data from biopsies performed on 2066 human blastocysts in 98 assisted reproduction laboratories around the world from September 2019 to January 2023.</p><p><strong>Participants/materials, setting, methods: </strong>This multicenter study included eligible patients undergoing IVF with preimplantation genetic testing (PGT), in which at least one embryo was diagnosed with a segmental aneuploidy. The mean maternal age was 36.4 years (SD 4.1), ranging from 25 to 44 years. These samples were processed on high-density SNP arrays. Chromosome level copy number and B allele frequency (BAF) plots from these embryos were used to determine segmental aneuploidy breakpoints. Known fragile sites catalogued by the HumCFS database were used for correlation analyses.</p><p><strong>Main results and the role of chance: </strong>Overall, a side-by-side pairing of observed breakpoints and known fragile sites demonstrated a strong concordance (r = 0.81, 95% CI [0.6, 0.92]). A chi-square test for independence for stratified groups showed a highly significant correlation between all observed breakpoints and known fragile sites (597 expected vs. 848 observed; P < 0.001) and for telomeric breaks alone (521 expected vs. 784 observed; P < 0.001). Observed interstitial breaks alone were not correlated to expected breakpoints (75 expected vs. 64 observed; P > 0.05).</p><p><strong>Limitations, reasons for caution: </strong>These findings should be interpreted with caution, as limitations in genomic resolution may bias detection and classification of smaller segmental aneuploidies. Additionally, this study touched upon the distribution of meiotic to mitotic breakpoints in human blastocysts as they relate to known fragile sites. Since meiotic aneuploidies increase with advanced maternal age and many IVF patients undergoing PGT-A testing fall in this category, a sampling bias should be considered for this specific metric.</p><p><strong>Wider implications of the findings: </strong>Demonstrating that segmental aneuploidies significantly correlate with known fragile sites highly susceptible to replication stress offers insight into the origin of subchromosomal imbalances and hints at the influence of stressors on reproductive success.</p><p><strong>Study funding
{"title":"Blastocyst segmental aneuploidy breakpoints are highly correlated with human genome fragile sites.","authors":"Elaine de Quadros, Jia Xu, Nathan Treff, Diego Marin, Arielle Freedman, Cristian Milevski, Kathleen Miller, Minglei Bian","doi":"10.1093/humrep/deaf151","DOIUrl":"10.1093/humrep/deaf151","url":null,"abstract":"<p><strong>Study question: </strong>Are segmental aneuploidies identified in human embryos more likely to occur within known fragile sites of the genome?</p><p><strong>Summary answer: </strong>Segmental breaks in the autosomes of human preimplantation embryos occur more frequently in known fragile areas of the genome.</p><p><strong>What is known already: </strong>Fragile sites represent specific loci in the genome characterized by inhibition of DNA synthesis when exposed to known inhibitors and are particularly sensitive to replication stress and instability.</p><p><strong>Study design, size, duration: </strong>This was a retrospective analysis of single nucleotide polymorphism (SNP) array-based preimplantation genetic testing data from biopsies performed on 2066 human blastocysts in 98 assisted reproduction laboratories around the world from September 2019 to January 2023.</p><p><strong>Participants/materials, setting, methods: </strong>This multicenter study included eligible patients undergoing IVF with preimplantation genetic testing (PGT), in which at least one embryo was diagnosed with a segmental aneuploidy. The mean maternal age was 36.4 years (SD 4.1), ranging from 25 to 44 years. These samples were processed on high-density SNP arrays. Chromosome level copy number and B allele frequency (BAF) plots from these embryos were used to determine segmental aneuploidy breakpoints. Known fragile sites catalogued by the HumCFS database were used for correlation analyses.</p><p><strong>Main results and the role of chance: </strong>Overall, a side-by-side pairing of observed breakpoints and known fragile sites demonstrated a strong concordance (r = 0.81, 95% CI [0.6, 0.92]). A chi-square test for independence for stratified groups showed a highly significant correlation between all observed breakpoints and known fragile sites (597 expected vs. 848 observed; P < 0.001) and for telomeric breaks alone (521 expected vs. 784 observed; P < 0.001). Observed interstitial breaks alone were not correlated to expected breakpoints (75 expected vs. 64 observed; P > 0.05).</p><p><strong>Limitations, reasons for caution: </strong>These findings should be interpreted with caution, as limitations in genomic resolution may bias detection and classification of smaller segmental aneuploidies. Additionally, this study touched upon the distribution of meiotic to mitotic breakpoints in human blastocysts as they relate to known fragile sites. Since meiotic aneuploidies increase with advanced maternal age and many IVF patients undergoing PGT-A testing fall in this category, a sampling bias should be considered for this specific metric.</p><p><strong>Wider implications of the findings: </strong>Demonstrating that segmental aneuploidies significantly correlate with known fragile sites highly susceptible to replication stress offers insight into the origin of subchromosomal imbalances and hints at the influence of stressors on reproductive success.</p><p><strong>Study funding","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1998-2007"},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply: Recurrent implantation failure: when study design fails before the embryos.","authors":"Qiong Wang, Xiaoran Zhang, Can Wang","doi":"10.1093/humrep/deaf171","DOIUrl":"10.1093/humrep/deaf171","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2022-2023"},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952027","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":"Recurrent implantation failure: when study design fails before the embryos.","authors":"Baris Ata, Erkan Kalafat, Paul Pirtea","doi":"10.1093/humrep/deaf170","DOIUrl":"10.1093/humrep/deaf170","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2020-2021"},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952033","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}
Josefa Maria Sanchez-Reyes, Antonio Parraga-Leo, Patricia Sebastian-Leon, Maria Del Carmen Vidal, Diana Marti-Garcia, Katharina Spath, Imma Sanchez-Ribas, Francisco Jose Sanz, Nuria Pellicer, Jose Remohi, Dagan Wells, Antonio Pellicer, Patricia Diaz-Gimeno
<p><strong>Study question: </strong>Can the disrupted window of implantation (WOI) be stratified according to transcriptomic patterns associated with reproductive success in IVF patients undergoing HRT?</p><p><strong>Summary answer: </strong>There are four transcriptomic patterns independent of endometrial timing associated with a gradient of reproductive prognosis underlying different molecular pathomechanisms.</p><p><strong>What is known already: </strong>A molecular heterogeneous profile independent of endometrial timing has been discovered as a cause of implantation failure that disrupt the endometrial transcriptome in the mid-secretory phase. However, the molecular heterogeneous patterns underlying the disruption remain poorly identify and understood. Characterizing the molecular heterogeneity of this endometrial disruption is crucial to develop personalized and more accurate diagnostic tools for preventive medicine, particularly for patients with a high risk of endometrial failure.</p><p><strong>Study design, size, duration: </strong>In this multicenter prospective study, 195 IVF patients undergoing HRT with endometrial biopsy collection, during mid-secretory phase for endometrial progression evaluation, were recruited between January 2019 and August 2022. Out of 195 patients, 131 were finally included in the following analysis.</p><p><strong>Participants/materials, setting, methods: </strong>Endometrial biopsies were processed for whole endometrial transcriptome analysis using RNA-Sequencing. To identify disruptions in the WOI, the transcriptomic variation due to cyclic endometrial tissue changes was removed. Out of 195 biopsies sequenced, 131 were derived from patients that met the clinical criteria to be classified as implantation failure group (≥3 implantation failures, n = 32) or control group (<3 implantation failures, n = 99). An artificial intelligence (AI) model, based on two supervised learning algorithms: support vector machine (SVM) and k-nearest neighbors (kNN), was performed with 131 patients that were randomly allocated to training (n = 105) and test (n = 26) sets for biomarker signature discovery and assessment of predictive performance, respectively. The reproductive outcomes of the single embryo transfer immediately after biopsy collection were analyzed. Differential expression and functional analyses were performed to characterize molecular profiles. Finally, a quantitative PCR (qPCR) assay was used to corroborate the differential expression of six potential biomarkers.</p><p><strong>Main results and the role of chance: </strong>With the dichotomous clinical classification of poor or good reproductive prognosis, there was no transcriptomic distinction between patients with a history of implantation failures during HRT endometrial preparation. Alternatively, using an AI model to stratify IVF patients based on the probability of endometrial disruption revealed molecular and clinical differences between patterns. Patients we
{"title":"Stratifying IVF population endometria using a prognosis gradient independent of endometrial timing†.","authors":"Josefa Maria Sanchez-Reyes, Antonio Parraga-Leo, Patricia Sebastian-Leon, Maria Del Carmen Vidal, Diana Marti-Garcia, Katharina Spath, Imma Sanchez-Ribas, Francisco Jose Sanz, Nuria Pellicer, Jose Remohi, Dagan Wells, Antonio Pellicer, Patricia Diaz-Gimeno","doi":"10.1093/humrep/deaf156","DOIUrl":"10.1093/humrep/deaf156","url":null,"abstract":"<p><strong>Study question: </strong>Can the disrupted window of implantation (WOI) be stratified according to transcriptomic patterns associated with reproductive success in IVF patients undergoing HRT?</p><p><strong>Summary answer: </strong>There are four transcriptomic patterns independent of endometrial timing associated with a gradient of reproductive prognosis underlying different molecular pathomechanisms.</p><p><strong>What is known already: </strong>A molecular heterogeneous profile independent of endometrial timing has been discovered as a cause of implantation failure that disrupt the endometrial transcriptome in the mid-secretory phase. However, the molecular heterogeneous patterns underlying the disruption remain poorly identify and understood. Characterizing the molecular heterogeneity of this endometrial disruption is crucial to develop personalized and more accurate diagnostic tools for preventive medicine, particularly for patients with a high risk of endometrial failure.</p><p><strong>Study design, size, duration: </strong>In this multicenter prospective study, 195 IVF patients undergoing HRT with endometrial biopsy collection, during mid-secretory phase for endometrial progression evaluation, were recruited between January 2019 and August 2022. Out of 195 patients, 131 were finally included in the following analysis.</p><p><strong>Participants/materials, setting, methods: </strong>Endometrial biopsies were processed for whole endometrial transcriptome analysis using RNA-Sequencing. To identify disruptions in the WOI, the transcriptomic variation due to cyclic endometrial tissue changes was removed. Out of 195 biopsies sequenced, 131 were derived from patients that met the clinical criteria to be classified as implantation failure group (≥3 implantation failures, n = 32) or control group (<3 implantation failures, n = 99). An artificial intelligence (AI) model, based on two supervised learning algorithms: support vector machine (SVM) and k-nearest neighbors (kNN), was performed with 131 patients that were randomly allocated to training (n = 105) and test (n = 26) sets for biomarker signature discovery and assessment of predictive performance, respectively. The reproductive outcomes of the single embryo transfer immediately after biopsy collection were analyzed. Differential expression and functional analyses were performed to characterize molecular profiles. Finally, a quantitative PCR (qPCR) assay was used to corroborate the differential expression of six potential biomarkers.</p><p><strong>Main results and the role of chance: </strong>With the dichotomous clinical classification of poor or good reproductive prognosis, there was no transcriptomic distinction between patients with a history of implantation failures during HRT endometrial preparation. Alternatively, using an AI model to stratify IVF patients based on the probability of endometrial disruption revealed molecular and clinical differences between patterns. Patients we","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1928-1937"},"PeriodicalIF":6.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834948","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}
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