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Associations of anti-Müllerian hormone with primordial follicle density and in vitro maturation outcomes in girls with transfusion-dependent thalassemia undergoing fertility preservation. 抗<s:1>勒氏激素与输血依赖型地中海贫血女孩保存生育能力的原始卵泡密度和体外成熟结果的关系
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-09-01 DOI: 10.1093/humrep/deag117
Weie Zhao, Xiaoping Liu, Yingchun Guo, Tingting Li, Haitao Zeng, Cong Fang, Xiaoyan Liang, Yujie Li, Jingjie Li
{"title":"Associations of anti-Müllerian hormone with primordial follicle density and in vitro maturation outcomes in girls with transfusion-dependent thalassemia undergoing fertility preservation.","authors":"Weie Zhao, Xiaoping Liu, Yingchun Guo, Tingting Li, Haitao Zeng, Cong Fang, Xiaoyan Liang, Yujie Li, Jingjie Li","doi":"10.1093/humrep/deag117","DOIUrl":"10.1093/humrep/deag117","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the association between serum anti-Müllerian hormone (AMH) levels, primordial follicle density (PFD), and ovarian tissue oocyte in vitro maturation (OTO -IVM) outcomes in pediatric and adolescent girls undergoing ovarian tissue cryopreservation (OTC) for fertility preservation (FP)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In pediatric and adolescent girls undergoing FP, serum AMH levels were not correlated with histological PFD, but were positively associated with oocyte yield and IVM outcomes, with each 1 ng/ml increase in AMH corresponding to a 14% increase in oocyte yield and a 3.50% increase in the maturation rate of IVM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Serum AMH is an established biomarker of ovarian reserve in adults, reflecting the number of antral follicles. However, its value as a surrogate of the primordial follicle pool in pediatric and adolescent girls remains uncertain due to limited data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This retrospective cohort study included 119 pediatric and adolescent girls with transfusion-dependent thalassemia (TDT) who underwent OTC between July 2021 and February 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The study included 119 girls with TDT undergoing FP prior to hematopoietic stem cell transplantation. Preoperative serum AMH levels were measured. Ovarian cortical tissue was obtained for OTC, with a small fraction analyzed histologically for PFD. Immature oocytes retrieved from the tissue underwent IVM. Multivariate regression analyses evaluated associations between AMH, PFD, oocyte yield, and oocyte maturation rates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Median preoperative AMH was 3.1 ng/ml (interquartile range: 1.9-4.4 ng/ml). AMH was not significantly associated with PFD (β = -0.04, 95% confidence interval [CI]: -0.12 to 0.03, P = 0.262). Higher AMH was positively correlated with increased oocyte yield (incidence rate ratio [IRR]: 1.14, 95% CI: 1.08-1.20; P &lt; 0.001) and improved maturation rates of IVM (β  =  3.50, 95% CI: 1.10-5.90; P = 0.005). Increasing age was associated with lower PFD (β = -0.07, 95% CI: -0.13 to -0.01, P = 0.032) and improved oocyte retrieval (IRR: 1.06, 95% CI: 1.02-1.11; P = 0.008) and maturation rates (β  =  2.52, 95% CI: 0.54-4.51; P = 0.013).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;The study's limitations include the retrospective design and the disease-specific TDT cohort, limiting generalizability to other patient groups or healthy individuals. The dissociation between AMH and PFD indicates that AMH should be interpreted cautiously in FP counseling. As OTO-IVM remains experimental, AMH alone is insufficient to guide fertility preservation decisions, and OTC remains the most established option in pediatric patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;In children and adolescents with TDT, AMH is positively ass","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1570-1580"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From evidence to vision-from Developments to Directions. 从证据到愿景——从发展到方向。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-09-01 DOI: 10.1093/humrep/deag122
Kirstine Kirkegaard, Emma J Andrew, Andrew C Williams, Chris Barratt
{"title":"From evidence to vision-from Developments to Directions.","authors":"Kirstine Kirkegaard, Emma J Andrew, Andrew C Williams, Chris Barratt","doi":"10.1093/humrep/deag122","DOIUrl":"10.1093/humrep/deag122","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1465"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondria-targeted therapeutic strategies in assisted reproduction: challenges and potential solutions. 辅助生殖中的线粒体靶向治疗策略:挑战和潜在的解决方案。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-09-01 DOI: 10.1093/humrep/deag118
Raziye Melike Yildirim, Gizem Nur Sahin, Richard T Scott, Emre Seli
{"title":"Mitochondria-targeted therapeutic strategies in assisted reproduction: challenges and potential solutions.","authors":"Raziye Melike Yildirim, Gizem Nur Sahin, Richard T Scott, Emre Seli","doi":"10.1093/humrep/deag118","DOIUrl":"10.1093/humrep/deag118","url":null,"abstract":"<p><p>Mitochondria are central to oocyte competence and early embryonic development, with roles that extend beyond energy production to include regulation of redox homeostasis, apoptosis and cellular aging. Mitochondrial dysfunction is increasingly recognized as a key contributor to diminished ovarian reserve, impaired embryo development, and accelerated reproductive aging. Mitochondria-targeted therapeutic strategies, including pharmacological approaches such as Coenzyme Q10, mitoquinone, resveratrol, rapamycin, and NAD+ precursors, as well as mitochondrial replacement techniques such as maternal spindle and pronuclear transfer, have shown promise in preclinical models; however, clinical outcomes remain heterogeneous and often inconclusive. This translational gap likely reflects critical limitations, including variability in therapeutic targets, suboptimal timing of intervention relative to oocyte development, and insufficiently powered or standardized clinical studies. Greater emphasis on well-defined, physiologically justified therapeutic targets, along with the use of physiologically relevant experimental systems, may improve therapeutic precision and efficacy. Rigorous evaluation of safety, particularly for interventions with pleiotropic effects or heritable consequences, remains essential. A more targeted, developmentally informed and systematically validated approach is needed to advance mitochondria-based therapies toward meaningful improvements in reproductive outcomes.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1497-1506"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mastering reproduction across the globe: the growing and sustained impact of master's degree programs in reproductive science and medicine. 在全球范围内掌握生殖:生殖科学和医学硕士学位课程日益增长和持续的影响。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-04 DOI: 10.1093/humrep/deag129
Lauren Ataman-Millhouse, Federica Lopes, Giulia Vigone, Nimra Chohan, Rebecca Willingham, Pamela Monahan, Leah E Simon, T Rajendra Kumar, Christopher L R Barratt, Raquel Romar, Sebastián Cánovas, Joaquín Gadea, María-Jiménez Movilla, María Alexandra Márquez Lema, Jennifer P Barfield, Francesca E Duncan
{"title":"Mastering reproduction across the globe: the growing and sustained impact of master's degree programs in reproductive science and medicine.","authors":"Lauren Ataman-Millhouse, Federica Lopes, Giulia Vigone, Nimra Chohan, Rebecca Willingham, Pamela Monahan, Leah E Simon, T Rajendra Kumar, Christopher L R Barratt, Raquel Romar, Sebastián Cánovas, Joaquín Gadea, María-Jiménez Movilla, María Alexandra Márquez Lema, Jennifer P Barfield, Francesca E Duncan","doi":"10.1093/humrep/deag129","DOIUrl":"https://doi.org/10.1093/humrep/deag129","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the sustained impact of master's programs in reproductive science and medicine in meeting the growing global demand for expertise in this field?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;This study provides quantitative data supporting the value of master's degree programs in providing students with educational experiences to meet the increasing demands for a well-trained workforce of reproductive scientists.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Master's programs focused on reproduction-ranging from animal science, clinical embryology, and reproductive health and biology-are expanding around the globe, providing students with a degree beyond the bachelor's or its equivalent and are an alternative or bridge to other advanced degrees. However, the impact of these programs in creating a well-trained next generation of reproductive scientists to support workforce needs and advance the field has not been systematically investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;We performed a web search to define the landscape of master's programs offered across the globe. We also convened a meeting (Global Perspectives: A Think Tank for MS Programs in Reproductive Science and Medicine at Northwestern University on 24-25 June 2024) to establish a network between four master's programs (two in the United States and two in Europe), including the Master at Northwestern University (USA), at University of Dundee (United Kingdom), at Colorado State University (USA), and at the University of Murcia (Spain). These programs are established at public and private institutions, are varied with respect to class size and duration, and span focus areas ranging from veterinary to human reproductive health to Assisted Reproductive Technologies (ART). We obtained and analyzed enrollment and outcome data from the four featured master's programs to determine the profile of students who pursue these master's degrees in reproductive science and determine how they contribute to the field post-degree.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The study relied on self-reported data from each participating program. The programs were selected because they represent a cross-section of established master's programs in reproduction that have collectively trained almost 1000 students since 2004. We analyzed enrollment and outcome data from these four established master's programs. Programs reported on student outcomes post-degree, including job categories, job titles, employers, and other impact (e.g. publications, awards and honors, and grants and independent funding).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Master's programs in reproduction and related fields are on the rise, with the number of programs having almost doubled from 73 in 2022 to 145 in 2025. The four featured programs reported on at least 9 years of retrospective data. The University of Murcia program started in 2004","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Psychological and physical effects of short-term discontinuation of feminizing gender-affirming hormone therapy among older transgender women: a within-subject clinical trial. 短期停止女性化性别确认激素治疗对老年变性妇女的心理和生理影响:一项受试者内临床试验
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag087
J O van Heesewijk, R E S Geels, M den Heijer, K M A Dreijerink, B P C Kreukels
{"title":"Psychological and physical effects of short-term discontinuation of feminizing gender-affirming hormone therapy among older transgender women: a within-subject clinical trial.","authors":"J O van Heesewijk, R E S Geels, M den Heijer, K M A Dreijerink, B P C Kreukels","doi":"10.1093/humrep/deag087","DOIUrl":"10.1093/humrep/deag087","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What are the psychological and physical effects of short-term discontinuation and subsequent reinitiation of feminizing gender-affirming hormone therapy (fGAHT) in older transgender women receiving long-term therapy?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Short-term fGAHT discontinuation increased estradiol deprivation-related symptoms while reinitiation showed opposite effects, and psychological well-being was not affected.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;With growing numbers of older transgender individuals, questions arise regarding the necessity of long-term continuation of fGAHT, particularly since cisgender women have low estradiol concentrations after menopause. However, data on the effects of fGAHT discontinuation in older transgender women are lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This within-subject clinical trial included 19 participants and was conducted in 2024 and 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Transgender women aged ≥55 years (median age 66 years), on fGAHT for ≥5 years (median 23 years), were recruited from the Center of Expertise on Gender Dysphoria, Amsterdam, the Netherlands. Estradiol deprivation-related symptoms, sleep quality, quality of life, mental health, and body image were assessed via questionnaires at baseline, 12 weeks after fGAHT discontinuation, and 12 weeks after reinitiation. Outcomes were analyzed using multilevel models. Differences were considered substantial based on 95% CIs and ≥10% change between measurements. Perceived psychological and physical changes and willingness to permanently discontinue fGAHT were also assessed via open-ended questions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Experiences varied, but after discontinuation, unfavorable mean changes were found for somato-vegetative symptoms (β 0.4, 95% CI -0.7 to 1.5, %Δ 11.5), sleep disturbance (OR 1.6, 95% CI 0.2 to 10.3, %Δ 10.7), and happiness to a lesser extent (β -0.5, 95% CI -0.9 to -0.1, %Δ -6.4). Reinitiation showed favorable changes for somato-vegetative and total estradiol deprivation-related symptoms (β -0.8, 95% CI -1.9 to 0.3, %Δ -22.1; β -3.0, 95% CI -4.8 to -1.2, %Δ -36.3), total sleep quality (β -0.7, 95% CI -1.5 to 0.2, %Δ -10.3), sleep onset latency (β -2.8, 95% CI -8.1 to 2.5, %Δ -14.9), and sleep disturbance (OR 0.1, 95% CI 0.0 to 1.0, %Δ -46.6). No mean differences were found for depressive symptoms, anxiety, quality of life, or body satisfaction. Perceived psychological and physical changes were diverse and generally aligned with known menopause-related changes. One participant wished to permanently stop fGAHT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;The study was not blinded or placebo-controlled, which may have introduced expectancy bias. The small clinical sample may limit generalizability to the broader population of transgender women.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1387-1396"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101363","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}
引用次数: 0
Endometriosis and the mental health burden: a registry-based study of redeemed prescriptions and psychiatric hospital contacts before and after diagnosis of endometriosis. 子宫内膜异位症和心理健康负担:一项基于登记的研究,在诊断子宫内膜异位症之前和之后,撤销处方和精神病医院接触。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag089
Marie Josiasen, Anna Melgaard, Bodil Hammer Bech, Karina Ejgaard Hansen, Dorte Rytter
{"title":"Endometriosis and the mental health burden: a registry-based study of redeemed prescriptions and psychiatric hospital contacts before and after diagnosis of endometriosis.","authors":"Marie Josiasen, Anna Melgaard, Bodil Hammer Bech, Karina Ejgaard Hansen, Dorte Rytter","doi":"10.1093/humrep/deag089","DOIUrl":"10.1093/humrep/deag089","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do women with endometriosis have a higher use of antidepressants and anxiolytics, and more frequent psychiatric hospital contacts due to depression or anxiety, before and after receiving their endometriosis diagnosis, compared with women without endometriosis?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Women with an endometriosis diagnosis redeemed more prescriptions for antidepressants and anxiolytics and had more psychiatric hospital contacts due to depression or anxiety both before and after endometriosis diagnosis compared with women without endometriosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Endometriosis is associated with an increased risk of anxiety and depression, but evidence on patterns before and after diagnosis is limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This national, retrospective, registry-based study included 136 842 Danish women aged 15-55 years between 1 January 2000 and 31 December 2019. Each woman was followed for up to 10 years before and 10 years after the index date.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;We identified 22 807 women with a first-time hospital-based diagnosis of endometriosis using density sampling. Each woman with endometriosis was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 114 035). Information on redeemed prescriptions and psychiatric hospital contacts was obtained from national registries and compared using negative binomial regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Women with an endometriosis diagnosis redeemed more prescriptions for antidepressants and anxiolytics and had more psychiatric hospital contacts due to depression or anxiety in the 20-year study window. Adjusted incidence rate ratios (IRRs) for antidepressants were 1.29 (95% CI 1.23-1.36) before and 1.40 (95% CI 1.34-1.47) after the index date, when adjusting for age, region of residence, highest educational level, household type, labor market affiliation, origin, and parity. For anxiolytics, IRRs were 1.16 (95% CI 1.05-1.28) before and 1.46 (95% CI 1.29-1.64) after the index date. For psychiatric hospital contacts, IRRs were 1.28 (95% CI 1.09-1.49) before and 1.41 (95% CI 1.22-1.63) after the index date. The association for antidepressants was quite stable over the study period, while the association for anxiolytics showed a significant increase right before the index date, and the associations for psychiatric hospital contacts increased around 5 years before the index date.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;It was not possible to include women who were treated for suspected endometriosis in general practice or women diagnosed with endometriosis solely by private gynecologists. Therefore, the results are only applicable to hospital-based diagnoses of endometriosis. Not all women with depression or anxiety receive pharmacological treatment or h","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1338-1349"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Third-generation sequencing enables accurate preimplantation genetic testing of monogenic defects for de novo variants and incomplete pedigrees. 第三代测序能够对新生变异和不完整谱系的单基因缺陷进行准确的植入前基因检测。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag082
Yiwei Fang, Yuqian Wang, Yuejuan Zhan, Xiaohui Zhu, Ying Kuo, Nan Wang, Shuo Guan, Shi Song, Mochen Ma, Ying Lian, Jin Huang, Xu Zhi, Ping Liu, Rong Li, Zhiqiang Yan, Jie Qiao, Liying Yan
{"title":"Third-generation sequencing enables accurate preimplantation genetic testing of monogenic defects for de novo variants and incomplete pedigrees.","authors":"Yiwei Fang, Yuqian Wang, Yuejuan Zhan, Xiaohui Zhu, Ying Kuo, Nan Wang, Shuo Guan, Shi Song, Mochen Ma, Ying Lian, Jin Huang, Xu Zhi, Ping Liu, Rong Li, Zhiqiang Yan, Jie Qiao, Liying Yan","doi":"10.1093/humrep/deag082","DOIUrl":"10.1093/humrep/deag082","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can preimplantation genetic testing for monogenic defects (PGT-M) be achieved by performing third-generation sequencing (TGS) only on the proband for families with de novo variants or incomplete pedigrees?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Whole-genome TGS facilitates a simplified PGT-M workflow by establishing reliable haplotypes solely from proband sequencing involving de novo variants or incomplete pedigrees.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;PGT-M enables the accurate exclusion of embryos carrying pathogenic variants. However, its application to de novo variants or incomplete pedigrees is hindered by haplotype phasing. Moreover, direct variant detection suffers from detection failure and erroneous genotyping due to uneven coverage and allele dropout caused by whole-genome amplification. Current solutions, such as gamete or embryo analysis and targeted TGS, remain constrained by procedural complexity and lack of universality across different genes and mutation types.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This prospective study enrolled 16 families requiring PGT-M with de novo variants or incomplete pedigrees at the Reproductive Medicine Center of Peking University Third Hospital from July 2023 to August 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;This study included 9 families with incomplete pedigrees and 7 families with de novo variants, covering 10 distinct disease-causing genes or regions. To assess the capability of TGS for haplotype phasing, we evaluated its performance regarding genomic coverage and the retrieval of informative single-nucleotide polymorphisms (SNPs). Haplotypes were constructed using proband TGS data, and linkage analysis was performed by integrating linked heterozygous SNPs with next-generation sequencing data from the couple and embryos to determine pathogenic status. Subsequently, we developed a simplified strategy that inferred inheritance by comparing heterozygous SNPs from the proband's haplotype directly against corresponding homozygous sites in the embryos. The diagnostic outcomes of this simplified workflow were statistically evaluated and compared with those of the standard TGS strategy to assess concordance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Phase blocks generated by TGS achieved &gt;75% coverage for the vast majority of OMIM genes, most of which contained more than 100 heterozygous informative SNPs located in the gene body and their 1 Mb flanking regions, indicating a wide range of applicability in a variety of gene variants. Haplotypes were successfully constructed for all 16 enrolled families using TGS data, with 14 families having completed embryo testing, while the 2 families withdrew due to personal reasons. To date, prenatal diagnosis via amniocentesis in three families has confirmed the fetuses to be free of pathogenic variants. A simplified strategy was further applied to 14 families ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1448-1463"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ABHD2 activity is not required for the non-genomic action of progesterone on human sperm. 孕酮对人类精子的非基因组作用不需要ABHD2活性。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag085
Madison Edwards, Alexandra Amaral, Eve M Carter, Oliver Arnolds, Karen Vester, Anna Thrun, Edvard Wigren, Evert Homan, Pauline Ribera, Kirsty Bentley, Martin Haraldsson, Nmesoma Theo-Emegano, Peter Loppnau, Magdalena M Szewczyk, Michelle A Cao, Dalia Barsyte-Lovejoy, Nicole Dittmar, Anika Hans, Mandy Weber, Jens Münchow, W Felix Zhu, Louisa Temme, Christoph Brenker, Timo Strünker, Michael Sundström, Matthew H Todd, Aled M Edwards, Ralf Lesche, Opher Gileadi, Claudia Tredup
{"title":"ABHD2 activity is not required for the non-genomic action of progesterone on human sperm.","authors":"Madison Edwards, Alexandra Amaral, Eve M Carter, Oliver Arnolds, Karen Vester, Anna Thrun, Edvard Wigren, Evert Homan, Pauline Ribera, Kirsty Bentley, Martin Haraldsson, Nmesoma Theo-Emegano, Peter Loppnau, Magdalena M Szewczyk, Michelle A Cao, Dalia Barsyte-Lovejoy, Nicole Dittmar, Anika Hans, Mandy Weber, Jens Münchow, W Felix Zhu, Louisa Temme, Christoph Brenker, Timo Strünker, Michael Sundström, Matthew H Todd, Aled M Edwards, Ralf Lesche, Opher Gileadi, Claudia Tredup","doi":"10.1093/humrep/deag085","DOIUrl":"10.1093/humrep/deag085","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is the hydrolase ABHD2 required for progesterone-induced Ca2+ influx via CatSper and the resulting motility responses in human sperm?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Progesterone-induced Ca2+ influx via CatSper and the resulting motility responses in human sperm do not require ABHD2 activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Sperm motility is tightly regulated by signalling pathways that are activated as sperm ascend the female reproductive tract, including progesterone triggering Ca2+ influx via the CatSper channel and inducing hyperactivated motility needed for fertilization. This process is thought to involve ABHD2, which may hydrolyze the endogenous CatSper inhibitor 2-arachidonoylglycerol (2-AG), thereby relieving inhibition and enabling calcium entry into the flagellum.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;Potent small molecule inhibitors of ABHD2 activity were synthesized, characterized, and used as tools to scrutinize the role of ABHD2 in activation of CatSper and regulation of sperm motility.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Derivatives of published ABHD2 inhibitors were optimized for in vitro potency and cellular activity and subsequently tested in human sperm motility and Ca2+ influx assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Progesterone does not activate ABHD2 in vitro. In addition, inhibition of ABHD2 in human sperm has no effect on progesterone-induced Ca2+ influx through CatSper nor on basal or progesterone-induced hyperactivated motility. This demonstrates that ABHD2 activity is, in fact, not required for the non-genomic action of progesterone on human sperm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;None.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;We examined the effects of inhibition of the enzymatic activity of ABHD2. We cannot exclude that ABHD2 functions as a part of a larger multiprotein complex, in which it may play a structural role independent of its hydrolase activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;This study presents conclusive evidence that ABHD2 does not bind progesterone and that its hydrolase activity is not required for progesterone activation of CatSper and resulting changes in motility of human sperm. These results highlight the need for further research to elucidate the mechanism underlying the non-genomic action of progesterone on human sperm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interest(s): &lt;/strong&gt;This publication is based on research funded by the Gates Foundation, reference IDs INV-040467 and ID INV-072213. The findings and conclusions contained within are those of the authors and do not necessarily reflect the positions or policies of the Gates Foundation. LT, CB, and TS were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-project numbers 329621271 (CRU326; CB, TS), and 404595355 (Research Training G","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1409-1419"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054176","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}
引用次数: 0
Obstetric outcomes after IVF/ICSI treatment in women with endometriosis and/or adenomyosis diagnosed by ultrasonography: a prospective cohort study. 超声诊断为子宫内膜异位症和/或子宫腺肌症的妇女接受IVF/ICSI治疗后的产科结局:一项前瞻性队列研究
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag084
Sara Alson, Kristina Mattsson, Povilas Sladkevicius
{"title":"Obstetric outcomes after IVF/ICSI treatment in women with endometriosis and/or adenomyosis diagnosed by ultrasonography: a prospective cohort study.","authors":"Sara Alson, Kristina Mattsson, Povilas Sladkevicius","doi":"10.1093/humrep/deag084","DOIUrl":"10.1093/humrep/deag084","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Among women pregnant after IVF/ICSI, do obstetric outcomes differ for women diagnosed with endometriosis and/or adenomyosis according to definitions by International Deep Endometriosis (IDEA) and the revised Morphological Uterus Sonographic Assessment (MUSA) groups, compared to women without the disease?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Women with endometriosis and/or adenomyosis have a higher risk of preterm birth, hypertensive disorders of pregnancy, placenta previa, antepartum hemorrhage, and pelvic pain, compared to women without.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Evidence regarding the impact of endometriosis and adenomyosis on obstetric outcomes remains inconsistent, largely due to heterogeneity in study design, diagnostic methods, disease criteria, and mode of conception. Therefore, clinical guidance on antenatal management for affected women remains limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This was a prospective, observational cohort study of 1035 women who underwent up to three consecutive IVF/ICSI treatments at a university hospital. Published data suggest a preterm birth risk of 8-10% after IVF/ICSI without endometriosis, with higher rates in endometriosis and adenomyosis. Assuming 10% versus 20% preterm birth, 492 women were needed for 80% power. In total, 666 women gave birth to a child between January 2019 and April 2024. Of these, 607 (91.1%) women, for which the obstetric outcomes were known, were included in the study, while the remaining 59 (8.9%) were lost to follow-up.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Eligible for publicly funded IVF/ICSI treatments are non-smoking women aged 25 to ≤39 years, with a BMI of 18 to &lt;30 kg/m2 and no previous children with the present partner. Women are entitled to up to three consecutive, publicly subsidized IVF/ICSI treatments, until the birth of the first child is achieved. All women underwent pretreatment ultrasound examination by an expert examiner, using the IDEA and revised MUSA definitions. Out of 607 included women, in total 144/607 (23.7%) women had endometriosis and/or adenomyosis. The primary outcome was preterm birth (delivery before completed 37 weeks gestation). Secondary outcomes included placenta previa, antepartum or postpartum hemorrhage, hypertensive disorders of pregnancy, gestational diabetes mellitus, caesarean section delivery, placental abruption, oligohydramnios, pelvic pain, and neonate small for gestational age, as well as outcomes stratified for women with different disease phenotypes. The adjusted relative risk for the different outcomes was calculated using modified Poisson regression analyses with robust error variances.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Preterm birth occurred in 27/144 (18.9%) women with endometriosis and/or adenomyosis compared to 53/463 (11.4%) in disease-free women, corresponding to an aRR 1.63 (95% CI, 1.06-2.49), ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1367-1376"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041827","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}
引用次数: 0
Donor-conceived adolescents' interest in obtaining information about their identity-release oocyte or sperm donor-results from the Swedish Study on Gamete Donation. 来自瑞典配子捐赠研究的结果显示,供体怀孕的青少年对获得有关其身份信息的兴趣——释放卵子或精子供体。
IF 6.8 1区 医学
Human reproduction Pub Date : 2026-08-01 DOI: 10.1093/humrep/deag088
Henrik Groundstroem, Johan Paulin, Emilia Thorup, Gunilla Sydsjö, Claudia Lampic
{"title":"Donor-conceived adolescents' interest in obtaining information about their identity-release oocyte or sperm donor-results from the Swedish Study on Gamete Donation.","authors":"Henrik Groundstroem, Johan Paulin, Emilia Thorup, Gunilla Sydsjö, Claudia Lampic","doi":"10.1093/humrep/deag088","DOIUrl":"10.1093/humrep/deag088","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do donor-conceived adolescents in lesbian- and heterosexual-couple families intend to request information about their identity-release oocyte or sperm donor?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;While more than half of adolescents intended to request donor information, being uncertain about making such requests was quite common, particularly among adolescents reporting better family functioning and those conceived with donor sperm in heterosexual-couple families.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Increasing numbers of children conceived with identity-release gamete donation are approaching the age when they can obtain donor information, but there is very little knowledge about their perspectives regarding this possibility, particularly among those conceived with donor oocytes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;The present cross-sectional survey study was conducted 2022-2023 as part of a longitudinal follow-up of lesbian- and heterosexual-couple families following identity-release sperm donation (SD-L, SD-H) or oocyte donation (OD-H). We approached parents in a total of 216 families with a survey and also requested their consent to contact their donor-conceived child, provided he/she was aware of the donor conception. Parents in 165 families participated in this follow-up and, among these, parents in 123 families (75%) also provided contact information to their child(ren). Out of 128 approached adolescents, 100 completed the survey (78% response rate). Following exclusion of four adolescents with known/directed donors, the study sample consisted of 96 donor-conceived children aged 13-16 years (47 SD-L, 27 SD-H, and 22 OD-H), most of whom had been aware of their donor conception from an early age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, method: &lt;/strong&gt;The present study was based on the fifth wave of data collection of the Swedish Study on Gamete Donation, which used consecutive recruitment of recipient couples starting donation treatment 2005-2008. In Sweden, recipients of donor gametes receive no information about the donor. Only the donor-conceived person has the legal right, when sufficiently mature, to request information about the donor, including his/her identity. Study-specific items were used to assess adolescents' experiences and perceptions of disclosure issues, interest in requesting any donor information (identifying and/or non-identifying) as well as interest in contact with the donor and same-donor peers. Family relationships were assessed with the FAD GF6+ and study-specific items measuring perceived parent-child closeness and resemblance. Comparisons between the three donation groups (SD-L, SD-H, OD-H) were performed with χ2 test and Fisher exact test. Multinomial logistic regression analysis was performed in two separate models to investigate if the intention to request donor information was associated with family type (lesbian/heterosexual-couple) and wi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1377-1386"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041881","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}
引用次数: 0
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