Human reproduction open最新文献_第5页

Association between novel per- and poly-fluoroalkyl substances and premature ovarian insufficiency: a case-control study. 新型单氟烷基和多氟烷基物质与卵巢早衰之间的关系：一项病例对照研究。

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-07-12 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf044

Rui Qiao, Fanghao Guo, Haixia Ding, Di Sun, Qianhui Hu, Yanquan Li, Meiling Zhang, Qing Zhang, Wen Li

Study question: Do novel per- and poly-fluoroalkyl substances (Novel PFAS) have associations with premature ovarian insufficiency (POI)?

Summary answer: Hexafluoropropylene oxide dimer acid (HFPO-DA), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluoropentanesulfonic acid (PFPeS) are associated with an increased risk of POI, and the effect is worse with exposure to mixtures.

What is known already: As public health concerns following Novel PFAS exposure are rising globally, there is a need to understand the exact association between Novel PFAS and various diseases. Epidemiologic studies suggest traditional PFAS exposures adversely affect women's reproductive health, but the association between exposure to Novel PFAS and POI remains unclear.

Study design size duration: A retrospective research study, including 371 women, with (case group, n = 151) and without POI (control group, n = 220), was conducted between June 2023 and May 2024.

Participants/materials setting methods: Thirteen types of Novel PFAS and basal concentrations of FSH, LH, estradiol (E2), and anti-Müllerian hormone (AMH) in plasma samples were measured in plasma samples collected during the early follicular phase (Days 2-5) of a natural menstrual cycle. In addition, characteristics of participants were collected. Both adjusted logistic regression and Bayesian kernel machine regression (BKMR) were used to evaluate associations between Novel PFAS (alone or as a mixture) and POI. Effect modification by age was also investigated.

Main results and the role of chance: The concentrations of HFPO-DA, PFBA, PFPeA, and PFPeS in the case group were significantly higher than in the reference group. The adjusted logistic regression models demonstrated positive associations between plasma concentrations of HFPO-DA, PFBA, PFPeA, and PFPeS with the risk of POI [OR_adj = 2.89 (95% CI: 1.84-4.53), 1.54 (95% CI: 1.17-2.02), 3.12 (95% CI: 2.20-4.43), and 2.07 (95% CI: 1.31-3.27), respectively, per 2.7-fold increase in Novel PFAS concentrations]. High concentrations of Novel PFAS showed a negative correlation with AMH and antral follicle count (AFC), but a positive correlation with FSH. After controlling for other covariates, HFPO-DA, PFBA, PFBS, PFPeA, and PFPeS were the major contributors based on the BKMR models.

Limitations reasons for caution: False positives cannot be ruled out. Therefore, experiments on PFBA, PFPeA, PFPeS, and HFPO-DA in vivo also need to be conducted in animal models.

Wider implications of the findings: Our study is the first to discover the impact of Novel PFAS on the incidence of POI, with an investigation of indicators such as AMH, FSH, and AFC. Considering increasingly severe environmental pollution, our research results provide a broader understanding of

研究问题：新型单氟烷基和多氟烷基物质（新型PFAS）与卵巢功能不全（POI）有关吗？摘要回答：六氟环氧丙烷二聚酸（HFPO-DA）、全氟丁酸（PFBA）、全氟戊酸（PFPeA）和全氟戊磺酸（PFPeS）与POI风险增加有关，接触混合物的影响更严重。已知情况：随着新型PFAS暴露后的公共卫生问题在全球范围内不断上升，有必要了解新型PFAS与各种疾病之间的确切联系。流行病学研究表明，传统的PFAS暴露会对妇女的生殖健康产生不利影响，但新型PFAS暴露与POI之间的关系尚不清楚。研究设计规模持续时间：在2023年6月至2024年5月期间进行了一项回顾性研究，包括371名女性，有（病例组，n = 151）和没有POI（对照组，n = 220）。参与者/材料设置方法：在自然月经周期的卵泡早期（2-5天）收集血浆样本，测量血浆样本中13种新型PFAS和FSH、LH、雌二醇（E2）和抗勒氏激素（AMH）的基础浓度。此外，还收集了参与者的特征。采用调整后的逻辑回归和贝叶斯核机回归（BKMR）来评估新型PFAS（单独或混合）与POI之间的关系。研究了年龄对效果的影响。主要结果及偶然性作用：病例组HFPO-DA、PFBA、PFPeA、PFPeS浓度显著高于对照组。调整后的logistic回归模型显示，HFPO-DA、PFBA、PFPeA和PFPeS的血浆浓度与POI风险呈正相关[ORadj = 2.89 （95% CI: 1.84-4.53）、1.54 （95% CI: 1.17-2.02）、3.12 （95% CI: 2.20-4.43）和2.07 (95% CI: 1.31-3.27)，每增加2.7倍的新型PFAS浓度]。高浓度的Novel PFAS与AMH、AFC呈负相关，与FSH呈正相关。在控制其他协变量后，基于BKMR模型，HFPO-DA， PFBA， PFBS， PFPeA和PFPeS是主要贡献者。注意的局限性：不能排除假阳性。因此，PFBA、PFPeA、PFPeS和HFPO-DA的体内实验还需要在动物模型中进行。研究结果的更广泛意义：我们的研究首次发现了新型PFAS对POI发病率的影响，并对AMH、FSH和AFC等指标进行了调查。考虑到日益严重的环境污染，我们的研究结果为环境内分泌干扰物对卵巢功能的影响提供了更广泛的认识，并建议育龄妇女应减少对新型PFAS的暴露。研究经费/竞争利益：国家重点研发项目（2022YFC2703002）、国家自然科学基金（U24A20658, 82371726）、上海市地方高水平高校创新科研团队（SHSMU-ZDCX20212200）、上海市医院发展中心基金（SHDC22022303, SHDC22022201）、上海交通大学医产交叉重点项目（YG2023ZD27）资助。中国红十字基金会生殖医学研究项目（HSZH2024GFYZQ）和上海市胚胎性疾病重点实验室开放基金项目（shelab2023ZD02）。资助者在研究设计、数据收集和分析、发表决定或手稿准备中没有任何作用。作者宣称他们没有竞争利益。试验注册号：无。

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引用次数: 0

Silk-Ovarioids: establishment and characterization of a human ovarian primary cell 3D-model system. 丝样卵巢：人类卵巢原代细胞3d模型系统的建立和表征。

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-07-10 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf042

Valentina Di Nisio, Tianyi Li, Zhijie Xiao, Kiriaki Papaikonomou, Anastasios Damdimopoulos, Ákos Végvári, Filipa Lebre, Ernesto Alfaro-Moreno, Mikael Pedersen, Terje Svingen, Roman Zubarev, Ganesh Acharya, Pauliina Damdimopoulou, Andres Salumets

Study question: What is the best protocol to establish a long-term stable three-dimensional (3D) model for human primary ovarian cells?Summary answer: We developed and characterized long-term cultured 3D models of primary ovarian somatic cells isolated from adult tissues, using Biosilk as a scaffold.What is known already: In vitro models that mimic ovaries are crucial for elucidating the biological mechanisms underlying follicle activation and growth, hormonal activity, ovarian angiogenesis, damage in response to toxic exposures, and other biological mechanisms that enable the functionality of this complex organ. Three-dimensional systems are particularly relevant because they replicate heterogeneity and cell-cell communication among different ovarian cell types. However, complex models using human ovarian primary cells are yet to be developed.Study design size duration: Ovarian tissue samples were collected from five patients (age 26 ± 5 years) who underwent gender-affirming surgery. The cortex and medulla were separated and dissociated into single-cell suspensions using mechanical and enzymatic methods. Three approaches were tested to establish a 3D model culture system: matrix-free ovarian spheroids (MFOS), a Matrigel-based three-layer gradient system (3LGS), and Biosilk scaffolds (Silk-Ovarioid). In parallel, paired controls from each patient and ovarian area were cultured in a standard 2D system for the same duration.Participants/materials setting methods: The 3D culture systems were monitored every second day to detect signs of aggregation and growth. Freshly fixed tissue, as well as 2D- and 3D-cultured samples were further processed for transcriptomic profiling after 42 days of culture using RNA sequencing. The culture of the 3D system was further characterized, regarding its protein profile and steroid and cytokine production, through proteomics and liquid chromatography-tandem mass spectrometry and the Luminex platform, respectively. The key findings from the high-throughput assays were finally validated through RNA fluorescent in situ hybridization (RNA-FISH) and immunofluorescence staining.Main results and the role of chance: The 3D model systems MFOS (n = 120) and 3LGS (n = 18) failed to form aggregates capable of long-term maintenance in culture (MFOS: maximum of 15 days for both cortex and medulla; 3LGS: maximum of 11 days for medulla only). In contrast, we successfully established ovarian cortex- and medulla-derived 3D systems using Biosilk, termed Silk-Ovarioids (n = 120). Silk-Ovarioids were maintained for up to 42 days as free-floating culture without any signs of cell death, as confirmed by the absence of TUNEL, γ-H2A.X, and cleaved caspase 3 fluorescent signals. The presence of key ovarian somatic cell types, including granulosa, stromal, endothelial, and perivascular cells,

研究问题：建立人类卵巢原代细胞长期稳定的三维（3D）模型的最佳方案是什么？我们开发并表征了从成人组织中分离的原代卵巢体细胞的长期培养3D模型，使用Biosilk作为支架。已知情况：模拟卵巢的体外模型对于阐明卵泡激活和生长、激素活性、卵巢血管生成、毒性暴露损伤以及其他使这一复杂器官发挥功能的生物学机制至关重要。三维系统尤其重要，因为它们复制了不同卵巢细胞类型之间的异质性和细胞间的通信。然而，使用人类卵巢原代细胞的复杂模型尚未开发。研究设计规模持续时间：收集5例接受性别确认手术的患者（年龄26±5岁）的卵巢组织样本。用机械和酶的方法将皮质和髓质分离并分离成单细胞悬浮液。采用无基质卵巢球体（MFOS）、基于基质的三层梯度系统（3LGS）和Biosilk支架（Silk-Ovarioid）三种方法建立3D模型培养体系。同时，来自每个患者和卵巢区域的配对对照在标准2D系统中培养相同的时间。参与者/材料设置方法：每隔一天监测三维培养系统，检测聚集和生长的迹象。新鲜固定的组织以及2D和3d培养的样本在培养42天后使用RNA测序进一步处理转录组分析。通过蛋白质组学、液相色谱-串联质谱和Luminex平台，对3D系统的培养进行了进一步的表征，包括蛋白质谱、类固醇和细胞因子的产生。高通量实验的关键发现最终通过RNA荧光原位杂交（RNA- fish）和免疫荧光染色进行验证。主要结果和机会的作用：3D模型系统MFOS （n = 120）和3LGS （n = 18）在培养中未能形成能够长期维持的聚集体(MFOS：皮质和髓质最多15天；3LGS：仅髓质最多11天)。相比之下，我们使用Biosilk成功地建立了卵巢皮层和髓质衍生的3D系统，称为Silk-Ovarioids （n = 120）。蚕丝卵巢作为自由漂浮培养维持了42天，没有任何细胞死亡的迹象，证实了TUNEL， γ-H2A的缺失。裂解caspase 3荧光信号。通过转录组学和蛋白质组学，在大多数类卵巢丝中证实了关键卵巢体细胞类型的存在，包括颗粒细胞、基质细胞、内皮细胞和血管周围细胞。通过RNA-FISH和免疫染色进行验证，使用以下标记物：颗粒细胞AMHR2，基质细胞PDGFRα，内皮细胞CLDN5和GPIHBP1，血管周围细胞GJA4/Cx37和MCAM。值得注意的是，通过转录组学和蛋白质组学数据以及缺氧标记物MMP2和PDGFRβ的表达，Silk-Ovarioids显示了促血管生成缺氧核心的形成。这种低氧环境导致培养4-6周后血管样结构的形成，血管生成标志物TGFBR2、BMP2和PDGFα呈阳性。通过鉴定新生细胞外基质分泌（Col1α1和Lamα1），以及检测培养基中促血管生成细胞因子（如IL-6、IL-8和GM-CSF）和类固醇（如孕烯醇酮和表甾酮），进一步证实了Silk-Ovarioids的功能。大规模数据：rna测序计数矩阵存放在Gene Expression Omnibus中，登录号为GSE253571。原始数据存储在瑞典国家数据服务中，DOI为https://doi.org/10.48723/h8cm-bs19。单细胞RNA-seq数据已从ArrayExpress数据库下载至EMBL-EBI，登录码为“E-MTAb - 8381”。质谱蛋白质组学数据已通过PRIDE合作伙伴存储库存储到ProteomeXchange Consortium，数据集标识符为PXD048710。用于分析的代码可在https://github.com/tialiv/Silk-Ovarioid_project.Limitations中找到：卵巢样本来自接受雄激素治疗的患者，这引起了人们的担忧，即与未接受雄激素刺激的患者相比，雄激素暴露可能会改变丝卵巢细胞的行为。此外，本研究中使用的细胞培养基中添加了胎牛血清，不含任何补充剂或生长因子，而这些补充剂或生长因子可能是使卵巢丝与原始组织相似所必需的。研究结果的更广泛含义：丝卵巢表现出低批次内变异性和长期培养稳定性，强调了它们作为开发生物工程、患者特异性人工卵巢的有力一步的潜力。此外，蚕丝卵巢可作为卵巢体外血管生成的第一个体外模型，作为体外卵泡生成的生物支架，并可用于针对卵巢的毒理学和药理学研究。研究经费/竞争利益：本研究由：卡罗林斯卡研究所创新医学中心（CIMED）的研究经费资助；欧盟地平线2020研究与创新计划（ERIN项目）952516);地平线欧洲基金(NESTOR，基金号：欧盟委员会（101120075）；瑞典可持续发展研究委员会FORMAS (2018-02280, 2020-01621)；资助：卡罗林斯卡研究所，瑞典研究委员会VR(批准号：2020 - 02132年);瑞典儿童癌症基金会（编号PR2017-0044， PR2020-0096）；爱沙尼亚研究理事会(批准号：PRG1076);瑞典研究委员会(批准号：2024 - 02530年);诺和诺德基金会(批准号：NNF24OC0092384);欧盟H2020项目信风尼亚（Sinfonia）857253) （INL研究）；和SbDToolBox，参考编号为Norte -01-0145-联邦-000047，由北葡萄牙区域业务方案（Norte 2020）根据《葡萄牙2020伙伴关系协定》通过欧洲区域发展基金（INL研究）提供支持。作者无利益冲突需要申报。

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引用次数: 0

Effects of different embryo culture media on birthweight following assisted reproductive technology. 不同胚胎培养基对辅助生殖技术后出生体重的影响。

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-07-09 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf041

Ming Li, Zhengyang Zhao, Qingqing Tao, Jin Huang, Ying Lian, Yue Li, Shengli Lin, Ping Liu, Qin Li, Rong Li, Jie Qiao

Study question: Does the type of embryo culture medium affect the birthweight of newborns conceived by ART?Summary answer: After fresh embryo transfers, singleton newborns in the G5 and HTF groups exhibited higher birthweight z-scores and increased risks of being large for gestational age (LGA) compared to those in the Cook group.What is known already: Current studies have not yet determined whether embryo culture medium affects birthweight and, if such an effect does exist, the significance of embryo culture medium among all the influencing factors is not yet clear.Study design size duration: A retrospective cohort study including 23 403 fresh ET cycles between 1 January 2010 and 31 December 2022 at the reproductive medical center of a university-affiliated hospital was conducted.Participants/materials setting methods: We performed a retrospective cohort study including 23 403 fresh ET cycles. Four embryo culture media were analyzed: Cook, G5-PLUS, G5, and HTF. Multiple linear regression analysis was used to evaluate potential associations between embryo culture medium and birthweight z-score. Logistic regression analysis was used to evaluate potential associations between embryo culture medium and the risk of LGA and macrosomia. Random forest models were constructed to conduct significance analysis of all factors that may affect birthweight z-score.Main results and the role of chance: The cohort comprised 4453, 8460, 7463, and 3027 singletons in the Cook, G5-PLUS, G5, and HTF groups, respectively. Compared to the Cook group, newborns in the G5 and HTF groups had higher birthweight z-scores (increased by 0.069 units, P < 0.001, and 0.073 units, P = 0.002, respectively) and higher risks of LGA (OR: 1.25, 95% CI: 1.12-1.39, P < 0.001; OR: 1.20, 95% CI: 1.05-1.37, P = 0.009, respectively), while newborns in the G5 group also had a higher risk of macrosomia (OR: 1.21, 95% CI: 1.06-1.39, P = 0.006). Of the main factors influencing birthweight, the embryo culture medium had a moderate significance.Limitations reasons for caution: Due to commercial and regulatory reasons, various culture media were used for different periods, thus resulting in the different number of cases for the four culture media groups.Wider implications of the findings: Our analysis revealed that the type of embryo culture medium directly affected birthweight z-scores and the risk of LGA and macrosomia in newborns conceived by ART. Consequently, the selection of embryo culture medium should be made cautiously. In addition, there's also a need for more post-market data on culture media for embryology labs.Study funding/competing interests: This study was supported by National Key Research and Development

研究问题：胚胎培养基的类型是否影响ART受孕新生儿的出生体重？摘要回答：在新鲜胚胎移植后，与库克组相比，G5组和HTF组的单胎新生儿表现出更高的出生体重z分数和更大的胎龄（LGA）风险。已知情况：目前的研究尚未确定胚胎培养基是否会影响出生体重，如果确实存在这种影响，那么胚胎培养基在所有影响因素中的重要性尚不清楚。研究设计规模持续时间：一项回顾性队列研究，包括2010年1月1日至2022年12月31日在一所大学附属医院生殖医学中心进行的23403个新鲜ET周期。参与者/材料设置方法：我们进行了一项回顾性队列研究，包括23403个新鲜ET周期。分析四种胚培养基：Cook、G5- plus、G5和HTF。采用多元线性回归分析评估胚胎培养基与出生体重z-score之间的潜在关联。采用Logistic回归分析评估胚胎培养基与LGA和巨大儿风险之间的潜在关联。构建随机森林模型，对所有可能影响出生体重z分数的因素进行显著性分析。主要结果及偶然性的作用：该队列在Cook组、G5- plus组、G5组和HTF组中分别有4453、8460、7463和3027个单胎。与Cook组相比，G5组和HTF组新生儿的出生体重z-score更高（分别增加0.069个单位，P = 0.002）， LGA的风险更高（OR: 1.25, 95% CI: 1.12-1.39, P = 0.009），而G5组新生儿的巨大儿风险也更高（OR: 1.21, 95% CI: 1.06-1.39, P = 0.006）。在影响出生重的主要因素中，胚培养基对出生重的影响中等。注意事项的局限性：由于商业和监管的原因，不同的文化媒介使用的时期不同，导致四个文化传媒集团的案例数量不同。研究结果的更广泛意义：我们的分析显示，胚胎培养基的类型直接影响ART受孕的新生儿出生体重z分数和LGA和巨大儿的风险。因此，应慎重选择胚培养基。此外，胚胎学实验室还需要更多的培养基上市后数据。研究经费/利益竞争：本研究由国家重点研发计划项目（2023YFC2705604和2024YFC2706900）和国家自然科学基金项目（82071721、82371706和82288102）资助。所有作者均无利益冲突需要报告。试验注册号：无。

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引用次数: 0

Correction to: The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes. 更正：线粒体DNA基因型、女性不孕症、卵巢反应和卵母细胞突变之间的相互作用。

IF 8.3 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-07-07 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf037

[This corrects the article DOI: 10.1093/hropen/hoae074.].

[更正文章DOI: 10.1093/hropen/hoae074.]。

引用次数: 0

Improving sperm selection strategies for assisted reproduction through closing the knowledge gap in sperm maturation mechanics. 通过缩小精子成熟机制的知识差距，改善辅助生殖的精子选择策略。

IF 8.3 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-07-03 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf040

Hanah May Hart, Brett Nixon, Jacinta Hope Martin, Robert John Aitken, Geoffry Nunzio De Iuliis

Background: Male factors contribute to ∼50% of all infertility cases globally and are a major contributor to escalating use of ART. In most instances, sub-fertile men retain the ability to produce spermatozoa, albeit with reduced quality and function. By necessity, an important feature of ART is the use of technologies that bypass the natural selection barriers that prevent poor-quality spermatozoa from participating in fertilization. This means that ART carries a significant risk of facilitating fertilization with poor-quality gametes harbouring undetected DNA damage and/or altered epigenomes. Such a scenario may account for the epidemiological links between the use of 'high intervention' technologies [e.g. ICSI] and an increased risk of adverse offspring outcomes. Such data highlight a pressing need for improved sperm selection tools that better mimic natural selection barriers, to ensure only the highest-quality spermatozoa are used for ART.Objective and rationale: Current sperm selection techniques for ART and the processes underpinning sperm maturation have often been considered independently and therefore reviewed separately. Here we outline the requirement for connecting research paradigms towards advancing clinical outcomes. This review highlights the importance of combining our advancing knowledge of sperm maturation biology with the pursuit of rational sperm selection strategies for the clinic; specifically, this narrative review summarizes the current clinical technologies used for sperm selection with a focus on their physiological relevance and limitations. We have given consideration to the events associated with sperm maturation and the importance of zona pellucida (ZP) binding as inspiration to inform the development of the next generation of sperm selection strategies. The connections and information presented should provide utility and interest for both clinicians and reproductive biologists alike.Search methods: The PubMed database was queried using the keywords: sperm selection/function/DNA quality/epigenome, ART, ICSI, male infertility, capacitation, zona pellucida, sperm-zona pellucida binding, DNA damage, and biofabrication. These keywords were combined with other relevant phrases. Literature was restricted to peer-reviewed articles in English (published between 1972 and 2024) with references within these articles also searched.Outcomes: During natural conception, high-quality sperm are 'selected', maximizing the chances of fertilization with healthy gametes carrying intact genomic/epigenetic cargo. This sub-population of spermatozoa possess the capacity to interact with the female reproductive tract and complete the suite of functional maturation processes required for successful fertilization and initiation of embryonic development. However, ART 'high intervention' strategies bypass these selective barriers leading to an increased

背景：男性因素占全球所有不孕症病例的50%，并且是ART使用升级的主要因素。在大多数情况下，低生育能力的男性保留了产生精子的能力，尽管质量和功能有所下降。ART的一个重要特点是，它使用的技术绕过了阻止劣质精子参与受精的自然选择障碍。这意味着抗逆转录病毒疗法有很大的风险促进受精，因为劣质配子含有未被发现的DNA损伤和/或改变的表观基因组。这种情况可能解释了“高干预”技术（如ICSI）的使用与不良后代结局风险增加之间的流行病学联系。这些数据突出表明，迫切需要改进精子选择工具，更好地模拟自然选择障碍，以确保只有最高质量的精子用于抗逆转录病毒治疗。目的和理由：目前用于抗逆转录病毒治疗的精子选择技术和支持精子成熟的过程经常被独立考虑，因此分别进行审查。在这里，我们概述了连接研究范式以推进临床结果的要求。这篇综述强调了将我们对精子成熟生物学的先进知识与对临床合理精子选择策略的追求相结合的重要性；具体来说，这篇综述总结了目前用于精子选择的临床技术，重点是它们的生理相关性和局限性。我们考虑了与精子成熟相关的事件和透明带（ZP）结合的重要性，以启发下一代精子选择策略的发展。所提供的联系和信息应该为临床医生和生殖生物学家提供实用和兴趣。检索方法：检索PubMed数据库，检索关键词：精子选择/功能/DNA质量/表观基因组、ART、ICSI、男性不育、获能、透明带、精子-透明带结合、DNA损伤和生物制造。这些关键词与其他相关短语组合在一起。文献仅限于同行评议的英文文章（发表于1972年至2024年之间），并检索了这些文章中的参考文献。结果：在自然受孕过程中，高质量的精子被“选择”，使携带完整基因组/表观遗传货物的健康配子受精的机会最大化。这个精子亚群具有与雌性生殖道相互作用的能力，并完成成功受精和胚胎发育启动所需的一整套功能成熟过程。然而，抗逆转录病毒治疗的“高干预”策略绕过了这些选择性障碍，导致无意中将基因组缺陷转移给后代的风险增加，并对后代的健康产生潜在的下游后果。这篇综述阐述了为什么目前的精子选择技术对ART后的活产率只提供了微小的改善。我们认为，利用精子-ZP结合（成功受精的倒数第二步）和新颖的ZP模拟技术，为临床选择具有受精能力的精子以改善ART提供了一个有吸引力但尚未得到充分研究的工具。注意的局限性：叙述性综述的结果解释存在偏倚风险，不能完全消除。文学局限于作者所说的语言：英语。更广泛的影响：抗逆转录病毒技术为不育夫妇提供了变革性的进步，然而，我们对自然受孕过程中如何“选择”最佳配子的基本理解存在差距，如果在临床受孕过程中得不到解释，就会给下一代带来继续依赖抗逆转录病毒技术和健康后果的风险。这篇文章的目的是将我们目前对精子成熟事件的了解和临床中这些细胞的当前选择策略结合起来。我们概述了通过我们对配子生物学的理解的进步以及人工配子选择新方法的发展来改善临床结果的潜力。研究经费/竞争利益：没有外部资助，但获得了澳大利亚纽卡斯尔大学环境与生命科学学院的财政支持。R.J.A.是Memphasys有限公司的科学顾问，这是一家对生殖健康感兴趣的生物技术公司，负责开发Felix™电泳精子分离设备。R.J.A.从Memphasys Ltd.获得薪水和补助金，并持有股份。其他作者声明没有利益冲突。

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引用次数: 0

Endometrial compaction shows no association with improved pregnancy outcomes in hormonal replacement frozen-thawed embryo transfer: an analysis of over 16 000 cases. 子宫内膜压实显示与激素替代冻融胚胎移植中妊娠结局的改善没有关联：一项超过16000例的分析。

IF 8.3 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf039

Peipei Pan, Chang Liu, Shiyi Lin, Haiqing Wang, Xia Chen, Haiyan Yang, Xuefeng Huang, Huan Zhang, Yili Teng

Study question: Is there an association between changes in endometrial thickness (EMT) following progesterone administration and pregnancy outcomes in frozen-thawed embryo transfers (FETs) at Day 3 (D3) and blastocyst stages?

Summary answer: Endometrial compaction is not associated with better pregnancy outcomes.

What is known already: Previous studies have shown conflicting results on the impact of EMT changes on FET outcomes.

Study design size duration: This study was a single-center retrospective cohort analysis of FETs from 1 January 2018 to 31 December 2022. A total of 9390 D3 FETs and 7063 blastocyst FETs were included during this period.

Participants/materials setting methods: D3 FETs and blastocyst FETs were divided into three groups: compaction group, non-change group, and expansion group. The impact of EMT changes after progesterone administration on HCG-positive, pregnancy, ongoing pregnancy, live birth, and pregnancy loss rates were analyzed for D3 and blastocyst FETs. EMT on the progesterone administration day (defined as EMT1) and on embryo transfer (ET)day (defined as EMT2) was measured exclusively by transvaginal ultrasound. Inverse probability weighting (IPW) and stratified logistic regressions were conducted to reduce the effects of confounding factors.

Main results and the role of chance: After IPW adjustment, in D3 FETs, women with compacted endometrium had the lowest HCG-positive rates (P = 0.012), clinical pregnancy rates (P < 0.001), ongoing pregnancy rates (P < 0.001), and live birth rates (LBRs) (P < 0.001) among the three groups. Among HCG-positive cases, the compaction group had the highest ectopic pregnancy rates (3.5% vs 2.6% vs 1.6%; P = 0.015) and the lowest LBRs (65.8% vs 68.3% vs 71.4%; P = 0.018). Univariate logistic regressions found that LBRs were weakly associated with compacted endometrium [odds ratio (OR) 0.831, 95% CI: 0.696-0.993]. Logistic regressions with IPW revealed that the compaction group was not associated with higher odds of pregnancy outcomes, including HCG positive, clinical pregnancy, ongoing pregnancy, ongoing pregnancy, and live births compared to the non-change group. In contrast, the expansion group was associated with higher odds of live birth per ETs (OR 1.166, 95% CI: 1.070-1.271; P = 0.001), and live birth per HCG-positive cases (OR 1.160, 95% CI: 1.028-1.309; P = 0.016). In blastocyst FETs, women with compacted endometrium had the lowest HCG-positive rates (P = 0.001) and clinical pregnancy rates (P = 0.031). Logistic regressions with IPW adjustment found that compaction group was associated with lower odds of HCG positive (OR 0.813, 95% CI: 0.668-0.989, P = 0.039) compared to the non-change group. Additionally, LBRs increased with the rising change ratios of EMT after progeste

研究问题：在第3天（D3）和囊胚期的冻融胚胎移植（fet）中，黄体酮给药后子宫内膜厚度（EMT）的变化与妊娠结局之间是否存在关联？总结回答：子宫内膜压实与更好的妊娠结局无关。已知情况：先前的研究显示，EMT变化对FET结果的影响结果相互矛盾。研究设计规模持续时间：本研究为2018年1月1日至2022年12月31日的单中心回顾性队列分析。在此期间共纳入9390个D3场效应管和7063个囊胚场效应管。受试者/材料设置方法：将D3型fet和囊胚型fet分为压实组、不变组和膨化组。分析孕酮给药后EMT变化对D3和囊胚fet的hcg阳性、妊娠、持续妊娠、活产率和流产率的影响。孕酮给药日（定义为EMT1）和胚胎移植（ET）日（定义为EMT2）的EMT仅通过阴道超声测量。采用逆概率加权（IPW）和分层逻辑回归来降低混杂因素的影响。主要结果及机会的作用：调整IPW后，D3 fet中，子宫内膜致密的妇女hcg阳性率最低（P = 0.012），临床妊娠率（P P P P = 0.015）， lbr最低(65.8% vs 68.3% vs 71.4%；p = 0.018)。单因素logistic回归发现，lbr与子宫内膜紧致性弱相关[比值比（OR） 0.831, 95% CI: 0.696-0.993]。与IPW的逻辑回归显示，与未改变组相比，压实组与妊娠结局（包括HCG阳性、临床妊娠、持续妊娠、持续妊娠和活产）的几率较高无关。相比之下，扩大组的每组ETs活产率较高(OR 1.166, 95% CI: 1.070-1.271；P = 0.001)，以及hcg阳性病例的活产率(OR 1.160, 95% CI: 1.028-1.309；p = 0.016)。在囊胚fet中，子宫内膜致密的妇女hcg阳性率最低（P = 0.001），临床妊娠率最低（P = 0.031）。经IPW调整后的Logistic回归发现，与未改变组相比，压实组HCG阳性的几率较低（OR 0.813, 95% CI: 0.668-0.989, P = 0.039）。此外，lbr随黄体酮给药后EMT变化率的升高而升高，但在一定范围内（D3组为30%，囊胚组为50%）。局限性：谨慎的原因：本研究仅包括对未经测试的胚胎进行fet的回顾性分析。研究结果的更广泛含义：D3 fet的子宫内膜扩张与lbr的改善呈正相关，但在囊胚fet中没有。这些发现表明，胚胎发育阶段特异性子宫内膜准备方案可能提高辅助生殖结果。研究经费/利益竞争：国家自然科学基金项目（82201856）、温州市科技局基础科研项目（Y20220006）、温州市生殖与遗传学重点实验室项目（2022HZSY0051）、浙江省医疗机构临床技术国际交流项目资助。作者无利益冲突需要申报。试验注册号：无。

{"title":"Endometrial compaction shows no association with improved pregnancy outcomes in hormonal replacement frozen-thawed embryo transfer: an analysis of over 16 000 cases.","authors":"Peipei Pan, Chang Liu, Shiyi Lin, Haiqing Wang, Xia Chen, Haiyan Yang, Xuefeng Huang, Huan Zhang, Yili Teng","doi":"10.1093/hropen/hoaf039","DOIUrl":"10.1093/hropen/hoaf039","url":null,"abstract":"Study question: Is there an association between changes in endometrial thickness (EMT) following progesterone administration and pregnancy outcomes in frozen-thawed embryo transfers (FETs) at Day 3 (D3) and blastocyst stages?Summary answer: Endometrial compaction is not associated with better pregnancy outcomes.What is known already: Previous studies have shown conflicting results on the impact of EMT changes on FET outcomes.Study design size duration: This study was a single-center retrospective cohort analysis of FETs from 1 January 2018 to 31 December 2022. A total of 9390 D3 FETs and 7063 blastocyst FETs were included during this period.Participants/materials setting methods: D3 FETs and blastocyst FETs were divided into three groups: compaction group, non-change group, and expansion group. The impact of EMT changes after progesterone administration on HCG-positive, pregnancy, ongoing pregnancy, live birth, and pregnancy loss rates were analyzed for D3 and blastocyst FETs. EMT on the progesterone administration day (defined as EMT1) and on embryo transfer (ET)day (defined as EMT2) was measured exclusively by transvaginal ultrasound. Inverse probability weighting (IPW) and stratified logistic regressions were conducted to reduce the effects of confounding factors.Main results and the role of chance: After IPW adjustment, in D3 FETs, women with compacted endometrium had the lowest HCG-positive rates (P = 0.012), clinical pregnancy rates (P < 0.001), ongoing pregnancy rates (P < 0.001), and live birth rates (LBRs) (P < 0.001) among the three groups. Among HCG-positive cases, the compaction group had the highest ectopic pregnancy rates (3.5% vs 2.6% vs 1.6%; P = 0.015) and the lowest LBRs (65.8% vs 68.3% vs 71.4%; P = 0.018). Univariate logistic regressions found that LBRs were weakly associated with compacted endometrium [odds ratio (OR) 0.831, 95% CI: 0.696-0.993]. Logistic regressions with IPW revealed that the compaction group was not associated with higher odds of pregnancy outcomes, including HCG positive, clinical pregnancy, ongoing pregnancy, ongoing pregnancy, and live births compared to the non-change group. In contrast, the expansion group was associated with higher odds of live birth per ETs (OR 1.166, 95% CI: 1.070-1.271; P = 0.001), and live birth per HCG-positive cases (OR 1.160, 95% CI: 1.028-1.309; P = 0.016). In blastocyst FETs, women with compacted endometrium had the lowest HCG-positive rates (P = 0.001) and clinical pregnancy rates (P = 0.031). Logistic regressions with IPW adjustment found that compaction group was associated with lower odds of HCG positive (OR 0.813, 95% CI: 0.668-0.989, P = 0.039) compared to the non-change group. Additionally, LBRs increased with the rising change ratios of EMT after progeste","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf039"},"PeriodicalIF":8.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variability and implications of recurrent implantation failure definitions used in the scientific literature: a systematic review. 科学文献中反复植入失败定义的可变性和含义：系统回顾。

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-06-18 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf033

Jessica K Lu, Yin Jun Law, Ning Zhang, Evangelia T Katsika, Efstratios M Kolibianakis, Christos A Venetis

Study question: How is recurrent implantation failure (RIF) defined in published literature and what is the prognostic agreement of these definitions with recently introduced RIF criteria by ESHRE?Summary answer: RIF definitions used in current clinical studies are highly variable and only a low proportion of published studies on RIF meet the ESHRE RIF diagnostic threshold.What is known already: RIF is a key cause of ART failure and growing focus of ART research. However, RIF remains poorly and inconsistently defined in published literature, thereby making the interpretation and clinical applicability of RIF research difficult and highly problematic.Study design size duration: The electronic databases EMBASE (Ovid), PubMed, Cochrane Central Register Of Controlled Trials (CENTRAL), Scopus, and Web of Science were systematically searched up to 30 June 2024 using the search terms 'recurrent implantation failure' and 'repeated implantation failure' for original peer-reviewed journal articles that included RIF patients.Participants/materials setting methods: The following data were manually extracted from eligible full-text articles: study methodology and characteristics, ART characteristics, and the RIF definition used. Extracted RIF definitions were analysed according to predetermined specifiers. The prognostic profile of these RIF definitions was compared with the 2023 ESHRE-recommended threshold for RIF diagnosis.Main results and the role of chance: The literature search identified 9853 studies, of which 748 were eligible for inclusion. Of these 748 studies, 589 studies (78.7%) provided one RIF definition, 83 studies (11.1%) used two definitions, three studies (0.4%) provided three or more definitions while 73 studies (9.8%) did not provide a definition for RIF. Of the 838 RIF definitions retrieved, there were a total of 503 unique RIF definitions. The three most common specifiers used to define RIF were embryo morphological quality (n = 491, 58.6% of RIF definitions), number of transfer events (n = 439, 52.4%), and cumulative number of embryos transferred (n = 326, 38.9%). RIF was most frequently diagnosed as 'failure of ≥3 embryo transfer events' (n = 26) and 'failure of ≥3 stimulated cycles' (n = 22). The threshold for defining RIF based on the cumulative number of embryos transferred in total was significantly higher for cleavage-stage embryos compared to blastocysts (incidence rate ratio 2.15, P < 0.001). In most cases, the RIF definitions used did not meet the ESHRE-recommended RIF diagnostic threshold of >60% cumulative predicted chance of implantation.Limitations reasons for caution: This systematic review excluded abstracts and case-series. Several studies provided RIF definitions with limited detail or ambiguous terminology with potential for misclassification or misint

研究问题：在已发表的文献中如何定义复发性植入失败（RIF），这些定义与ESHRE最近引入的RIF标准的预后一致性如何？总结回答：目前临床研究中使用的RIF定义是高度可变的，只有一小部分已发表的RIF研究符合ESHRE RIF诊断阈值。已知情况：RIF是抗逆转录病毒治疗失败的主要原因，也是抗逆转录病毒治疗研究日益关注的焦点。然而，在已发表的文献中，RIF的定义仍然很差且不一致，从而使RIF研究的解释和临床适用性变得困难且存在很大问题。研究设计规模持续时间：系统地检索电子数据库EMBASE （Ovid）、PubMed、Cochrane Central Register Of Controlled Trials （Central）、Scopus和Web Of Science，检索词为“复发性植入失败”和“重复植入失败”，检索到2024年6月30日之前包括RIF患者的同行评审期刊文章。参与者/材料设置方法：从符合条件的全文文章中手动提取以下数据：研究方法和特征、ART特征和使用的RIF定义。提取的RIF定义根据预定的说明符进行分析。这些RIF定义的预后概况与2023年eshre推荐的RIF诊断阈值进行了比较。主要结果及偶然性的作用：文献检索共发现9853项研究，其中748项符合纳入条件。在这748项研究中，589项研究（78.7%）提供了一个RIF定义，83项研究（11.1%）使用了两个定义，3项研究（0.4%）提供了三个或更多定义，73项研究（9.8%）没有提供RIF的定义。在检索到的838个RIF定义中，总共有503个唯一的RIF定义。用于定义RIF的三个最常见的指标是胚胎形态质量（n = 491，占RIF定义的58.6%）、转移事件数（n = 439, 52.4%）和累计移植胚胎数（n = 326, 38.9%）。RIF最常被诊断为“≥3个胚胎移植事件失败”（n = 26）和“≥3个刺激周期失败”（n = 22）。卵裂期胚胎以累计移植胚胎总数定义RIF的阈值明显高于囊胚（发生率比为2.15，P为60%）。局限性：本系统综述排除了摘要和病例系列。一些研究提供的RIF定义细节有限或术语模糊，有可能被错误分类或误解。研究结果的更广泛含义：目前临床研究中使用的RIF定义之间仍然存在高度的可变性和差异。此外，满足ESHRE RIF诊断阈值的研究比例较低，这让人怀疑这些研究中的人群是否真正是RIF患者。因此，应谨慎解读已发表的研究结果。为了使RIF病因学和治疗干预的未来研究具有更广泛的临床适用性，必须仔细实施标准化的RIF定义。研究资金/竞争利益：本研究未寻求或获得特定的外部资金。所有作者均报告本研究无利益冲突。试验注册号：该试验在PROSPERO注册（CRD42022295349）。

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引用次数: 0

Why does the recurrent implantation failure literature need to be rewritten? 为什么反复植入失败的文献需要重写？

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-06-18 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf035

Baris Ata

引用次数: 0

Association between trace metal element concentrations in human blood plasma and early MAR embryological outcomes: a couple-based prospective cohort study. 人血浆中微量金属元素浓度与早期MAR胚胎结局之间的关系：一项基于夫妇的前瞻性队列研究。

IF 11.1 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-06-10 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf034

Yawen Cao, Shuangshuang Bao, Qianhui Yang, Yaning Sun, Yanlan Tang, Wei Ju, Junjun Liu, Wenbin Fang, Xuemei Wang, Caiyun Wu, Chaojie Li, Peng Zhu, Shanshan Shao, Fangbiao Tao, Guixia Pan

Study question: What are the effects of plasma trace metal element exposure on early embryological outcomes of IVF in couples?

Summary answer: Exposure to plasma trace metal elements before treatment is associated with early embryological outcomes of IVF in couples and both partners, with both harmful and beneficial effects on embryonic development.

What is known already: Trace metal element exposure is one of the strongest determinants of IVF outcomes, but existing studies have certain limitations, such as the limited range of trace metal elements considered, and most have focused only on maternal exposure, overlooking the contribution of paternal exposure. Few studies have explored the association between trace metal elements and early embryological outcomes of IVF from the couples' perspective.

Study design size duration: This couple-based prospective cohort study included a total of 1071 couples who underwent 1369 IVF treatment cycles between December 2020 and August 2023.

Participants/materials setting methods: Plasma concentrations of 21 trace metal elements were measured by an inductively coupled plasma mass spectrometer. Early IVF embryological outcomes included two-pronuclear (2PN) zygote numbers, best-quality embryo numbers, fertilization rates, and blastocyst numbers. Elastic net regression was employed to identify trace metal elements associated with early IVF embryological outcomes in both partners and couples. K-medoids clustering was used to identify the exposure patterns of trace metal elements in couples and both partners. Joint effects of trace metal mixtures were evaluated using quantile-based g-computation (QGC) and group-weighted quantile sum (groupWQS), while independent effects of individual trace metal element were assessed using the generalized linear mixed model.

Main results and the role of chance: In our study, the mean (SD) age was 32.60 (5.22) years for females and 33.79 (5.89) for males. The detection rates for all elements, except for beryllium (Be), exceeded 90%. High exposure to trace metal element mixtures in couples and male partners was associated with decreased numbers of best-quality embryos and blastocysts. Using QGC and groupWQS, we identified both harmful and beneficial metal mixtures that influence successful embryo development. Additionally, specific plasma trace metals such as iron (Fe), lithium (Li), strontium (Sr), and molybdenum (Mo) were positively associated with embryological outcomes, while metals like silver (Ag) and thallium (Tl) had adverse effects.

Limitations reasons for caution: We were limited by assessing plasma trace metal elements at a single time point, focusing only on fresh embryo transfer cycles, and being unable to control for unmeasured confounding factors (e.g. psychological factors and self-reported health conditions). Mor

研究问题：血浆微量金属元素暴露对夫妇体外受精早期胚胎学结果的影响是什么？摘要回答：治疗前接触血浆微量金属元素与夫妇及双方体外受精的早期胚胎结局有关，对胚胎发育既有有害的影响，也有有益的影响。已知情况：微量金属元素暴露是体外受精结果的最强决定因素之一，但现有的研究有一定的局限性，例如所考虑的微量金属元素范围有限，而且大多数研究只关注母亲的暴露，忽视了父亲暴露的作用。很少有研究从夫妇的角度探讨微量金属元素与体外受精早期胚胎结局之间的关系。研究设计规模持续时间：这项基于夫妇的前瞻性队列研究共包括1071对夫妇，他们在2020年12月至2023年8月期间接受了1369个试管婴儿治疗周期。参与者/材料设置方法：采用电感耦合等离子体质谱仪测定21种微量金属元素的血浆浓度。早期IVF胚胎学结果包括双原核（2PN）受精卵数量、最佳质量胚胎数量、受精率和囊胚数量。弹性网回归用于确定与早期IVF胚胎学结果相关的微量金属元素。采用k - medioids聚类分析方法确定了夫妻及双方的微量金属元素暴露模式。采用基于分位数的g-计算（QGC）和群体加权分位数和（groupWQS）评价微量金属混合物的联合效应，采用广义线性混合模型评价单个微量金属元素的独立效应。主要结果及偶然性的作用：本研究中，女性平均（SD）年龄为32.60（5.22）岁，男性平均（SD）年龄为33.79（5.89）岁。除铍（Be）外，其余元素的检出率均超过90%。夫妻和男性伴侣高度接触微量金属元素混合物与优质胚胎和囊胚数量减少有关。通过QGC和群wqs，我们确定了影响胚胎成功发育的有害和有益的金属混合物。此外，特定的血浆微量金属，如铁（Fe）、锂（Li）、锶（Sr）和钼（Mo）与胚胎结局呈正相关，而银（Ag）和铊（Tl）等金属则有不利影响。局限性：我们的局限性在于在单个时间点评估血浆微量金属元素，仅关注新鲜胚胎移植周期，并且无法控制未测量的混杂因素（例如心理因素和自我报告的健康状况）。此外，由于我们的研究对象是接受体外受精的夫妇，因此我们的结果外推需要谨慎。研究结果的更广泛意义：这些发现强调了对计划怀孕的夫妇实施孕前微量元素筛查和有针对性的微量元素干预的重要性，作为优化生殖健康和体外受精结果的策略。研究经费/利益竞争：国家重点研发计划项目（No. 2018YFC1004201）、国家自然科学基金项目（No. 82304159）、国家卫生健康委员会出生缺陷预防重点实验室和河南省人口缺陷预防重点实验室开放研究基金（No. 8304159）资助。ZD202310)。所有作者声明无利益冲突。试验注册号：无。

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引用次数: 0

Correction to: Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase). 更正：出生缺陷报告和地屈孕酮的使用：来自世界卫生组织药物警戒数据库（VigiBase）的歧化分析。

IF 8.3 Q1 OBSTETRICS & GYNECOLOGY

Human reproduction open

Pub Date : 2025-06-03 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoaf029

[This corrects the article DOI: 10.1093/hropen/hoae072.].

[这更正了文章DOI: 10.1093/hropen/hoae072。]

引用次数: 0