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AI predictive models and advancements in microdissection testicular sperm extraction for non-obstructive azoospermia: a systematic scoping review. 人工智能预测模型和非阻塞性无精子症显微解剖睾丸精子提取的进展：系统范围综述。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-21 eCollection Date: 2025-01-01 DOI: 10.1093/hropen/hoae070
Hossein Jamalirad, Mahdie Jajroudi, Bahareh Khajehpour, Mohammad Ali Sadighi Gilani, Saeid Eslami, Marjan Sabbaghian, Hassan Vakili Arki
<p><strong>Study question: </strong>How accurately can artificial intelligence (AI) models predict sperm retrieval in non-obstructive azoospermia (NOA) patients undergoing micro-testicular sperm extraction (m-TESE) surgery?</p><p><strong>Summary answer: </strong>AI predictive models hold significant promise in predicting successful sperm retrieval in NOA patients undergoing m-TESE, although limitations regarding variability of study designs, small sample sizes, and a lack of validation studies restrict the overall generalizability of studies in this area.</p><p><strong>What is known already: </strong>Previous studies have explored various predictors of successful sperm retrieval in m-TESE, including clinical and hormonal factors. However, no consistent predictive model has yet been established.</p><p><strong>Study design size duration: </strong>A comprehensive literature search was conducted following PRISMA-ScR guidelines, covering PubMed and Scopus databases from 2013 to 15 May 2024. Relevant English-language studies were identified using Medical Subject Headings (MeSH) terms. We also used PubMed's 'similar articles' and 'cited by' features for thorough bibliographic screening to ensure comprehensive coverage of relevant literature.</p><p><strong>Participants/materials setting methods: </strong>The review included studies on patients with NOA where AI-based models were used for predicting m-TESE outcomes, by incorporating clinical data, hormonal levels, histopathological evaluations, and genetic parameters. Various machine learning and deep learning techniques, including logistic regression, were employed. The Prediction Model Risk of Bias Assessment Tool (PROBAST) evaluated the bias in the studies, and their quality was assessed using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines, ensuring robust reporting standards and methodological rigor.</p><p><strong>Main results and the role of chance: </strong>Out of 427 screened articles, 45 met the inclusion criteria, with most using logistic regression and machine learning to predict m-TESE outcomes. AI-based models demonstrated strong potential by integrating clinical, hormonal, and biological factors. However, limitations of the studies included small sample sizes, legal barriers, and challenges in generalizability and validation. While some studies featured larger, multicenter designs, many were constrained by sample size. Most studies had a low risk of bias in participant selection and outcome determination, and two-thirds were rated as low risk for predictor assessment, but the analysis methods varied.</p><p><strong>Limitations reasons for caution: </strong>The limitations of this review include the heterogeneity of the included research, potential publication bias and reliance on only two databases (PubMed and Scopus), which may limit the scope of the findings. Additionally, the absence of a meta-analysis prevents quantit
研究问题：人工智能（AI）模型预测接受微睾丸精子提取（m-TESE）手术的非阻塞性无精子症（NOA）患者的精子提取有多准确？摘要回答：人工智能预测模型在预测接受m-TESE的NOA患者成功取精方面具有重要的前景，尽管研究设计的可变性、小样本量和缺乏验证性研究等方面的局限性限制了该领域研究的总体可推广性。已知情况：先前的研究已经探索了m-TESE中成功取精的各种预测因素，包括临床和激素因素。然而，尚未建立一致的预测模型。研究设计规模持续时间：根据PRISMA-ScR指南进行全面的文献检索，涵盖PubMed和Scopus数据库，时间为2013年至2024年5月15日。使用医学主题标题（MeSH）术语确定相关的英语研究。我们还使用PubMed的“类似文章”和“被引用”特征进行全面的书目筛选，以确保全面覆盖相关文献。参与者/材料设置方法：本综述纳入了NOA患者的研究，其中基于人工智能的模型通过结合临床数据、激素水平、组织病理学评估和遗传参数来预测m-TESE结果。采用了各种机器学习和深度学习技术，包括逻辑回归。预测模型偏倚风险评估工具（PROBAST）评估了研究中的偏倚，并使用透明报告个体预后或诊断多变量预测模型（TRIPOD）指南对其质量进行了评估，以确保可靠的报告标准和方法的严谨性。主要结果和偶然性的作用：在筛选的427篇文章中，45篇符合纳入标准，其中大多数使用逻辑回归和机器学习来预测m-TESE结果。基于人工智能的模型通过整合临床、激素和生物因素显示出强大的潜力。然而，研究的局限性包括样本量小、法律障碍以及在推广和验证方面的挑战。虽然一些研究采用了更大的多中心设计，但许多研究受到样本量的限制。大多数研究在参与者选择和结果确定方面具有低偏倚风险，三分之二的研究在预测因子评估中被评为低风险，但分析方法各不相同。局限性：本综述的局限性包括纳入研究的异质性、潜在的发表偏倚以及仅依赖两个数据库（PubMed和Scopus），这可能会限制研究结果的范围。此外，缺乏荟萃分析妨碍了对模型一致性的定量评估。尽管如此，该综述为noaa中m-TESE的人工智能预测模型提供了有价值的见解。研究结果的更广泛意义：该综述强调了先进的人工智能技术在预测接受m-TESE的NOA患者成功取精方面的潜力。通过整合临床、激素、组织病理学和遗传因素，人工智能模型可以增强决策能力，改善患者预后，减少手术失败的次数。然而，为了进一步提高人工智能预测在生殖医学中的准确性和可靠性，未来的研究应通过纳入更大的样本量并进行前瞻性验证试验来解决当前的局限性。这种持续的研究和开发对于加强人工智能模型的适用性和确保更广泛的临床应用至关重要。研究经费/竞争利益：作者感谢伊朗马什哈德医学科学大学（Mashhad University of Medical Sciences, Mashhad, Iran）的资金支持（Grant ID: 4020802）。作者声明没有利益冲突。注册号：无。
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引用次数: 0
A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure. 对精子发生相关位点常见和罕见遗传变异的综合研究发现了特发性严重生精功能障碍的新风险因素。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae069
Andrea Guzmán-Jiménez, Sara González-Muñoz, Miriam Cerván-Martín, Nicolás Garrido, José A Castilla, M Carmen Gonzalvo, Ana Clavero, Marta Molina, Saturnino Luján, Samuel Santos-Ribeiro, Miguel Ángel Vilches, Andrea Espuch, Vicente Maldonado, Noelia Galiano-Gutiérrez, Esther Santamaría-López, Cristina González-Ravina, Fernando Quintana-Ferraz, Susana Gómez, David Amorós, Luis Martínez-Granados, Yanira Ortega-González, Miguel Burgos, Iris Pereira-Caetano, Ozgur Bulbul, Stefano Castellano, Massimo Romano, Elena Albani, Lluís Bassas, Susana Seixas, João Gonçalves, Alexandra M Lopes, Sara Larriba, Rogelio J Palomino-Morales, F David Carmona, Lara Bossini-Castillo
<p><strong>Study question: </strong>Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?</p><p><strong>Summary answer: </strong>Our findings revealed a significant association between SPGF and the <i>SHOC1</i> gene and identified three novel genes (<i>PCSK4</i>, <i>AP3B1</i>, and <i>DLK1</i>) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.</p><p><strong>What is known already: </strong>SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants. Next-generation sequencing methods are useful for identifying rare mutations that explain monogenic forms of SPGF. Genome-wide association studies (GWASs) have become essential approaches for deciphering the intricate genetic landscape of complex diseases, offering a cost-effective and rapid means to genotype millions of genetic variants. Novel methods have demonstrated that GWAS datasets can be used to infer rare coding variants that are causal for male infertility phenotypes. However, this approach has not been previously applied to characterize the genetic component of a whole case-control cohort.</p><p><strong>Study design size duration: </strong>We employed a hypothesis-driven approach focusing on all genetic variation identified, using a GWAS platform and subsequent genotype imputation, encompassing over 20 million polymorphisms and a total of 1571 SPGF patients and 2431 controls. Both common (minor allele frequency, MAF > 0.01) and rare (MAF < 0.01) variants were investigated within a total of 1797 loci with a reported role in spermatogenesis. This gene panel was meticulously assembled through comprehensive searches in the literature and various databases focused on male infertility genetics.</p><p><strong>Participants/materials setting methods: </strong>This study involved a European cohort using previously and newly generated data. Our analysis consisted of three independent methods: (i) variant-wise association analyses using logistic regression models, (ii) gene-wise association analyses using combined multivariate and collapsing burden tests, and (iii) identification and characterisation of highly damaging rare coding variants showing homozygosity only in SPGF patients.</p><p><strong>Main results and the role of chance: </strong>The variant-wise analyses revealed an association between SPGF and <i>SHOC1</i>-rs12347237 (<i>P </i>=<i> </i>4.15E-06, odds ratio = 2.66), which was likely explained by an altered binding affinity of key transcription factors in regulatory regions and the disruptive effect of coding variants within the gene. Three additional genes (<i>PCSK4</i>, <i>AP3B1</i>, and <i>DLK1</i>) were identified as novel relevan
研究问题：能否采用假设驱动法分析全基因组基因分型数据，以加深对男性不育症中严重生精功能障碍（SPGF）遗传基础的了解？我们的研究结果揭示了SPGF与SHOC1基因之间的显著关联，并发现了3个新基因（PCSK4、AP3B1和DLK1）以及30个基因中的32个潜在致病性罕见变异，它们都是导致这种情况的原因：SPGF是导致男性不育的一个主要原因，通常病因不明。SPGF可能是由多因素引起的，包括多个基因中的常见遗传变异和环境因素，也可能是由具有高度破坏性的罕见变异引起的。下一代测序方法有助于确定可解释单基因型 SPGF 的罕见变异。全基因组关联研究（GWAS）已成为破译复杂疾病错综复杂的遗传图谱的重要方法，为数百万基因变异的基因分型提供了一种具有成本效益的快速手段。新方法证明，GWAS 数据集可用于推断与男性不育表型有因果关系的罕见编码变异。然而，这种方法以前从未用于描述整个病例对照队列的遗传成分：我们采用了一种假设驱动的方法，利用 GWAS 平台和随后的基因型估算，重点研究已发现的所有遗传变异，其中包括超过 2000 万个多态性，共有 1571 名 SPGF 患者和 2431 名对照。共调查了 1797 个基因位点中的常见变异（小等位基因频率，MAF > 0.01）和罕见变异（MAF < 0.01），这些变异据报道在精子发生过程中发挥作用。该基因组是通过对男性不育遗传学方面的文献和各种数据库进行全面检索后精心组建的：这项研究涉及一个欧洲队列，使用了以前和新产生的数据。我们的分析包括三种独立的方法：(i) 使用逻辑回归模型进行变异关联分析；(ii) 使用多变量和折叠负荷测试进行基因关联分析；(iii) 识别仅在 SPGF 患者中出现同源变异的高损伤性罕见编码变异并确定其特征：变异分析表明，SPGF 与 SHOC1-rs12347237 存在关联（P = 4.15E-06，几率 = 2.66），其原因可能是关键转录因子在调控区域的结合亲和力发生了改变，以及基因内编码变异的破坏作用。通过基因累加检验法，我们还发现另外三个基因（PCSK4、AP3B1 和 DLK1）与人类男性不育症有新的关联（P 5.56E-04）。此外，我们还将所选基因的 32 个潜在致病性和隐性编码变异与 35 个不同病例联系起来：大规模数据：可通过 GWAS 目录公开获取（登录号：GCST90239721）：对低频变异的分析在获得足够的统计能力以检测遗传关联方面存在挑战。因此，要复制我们的结果，必须进行样本量更大的独立研究。此外，应通过功能实验来评估已鉴定变异在 SPGF 致病机制中的具体作用：我们的研究结果凸显了利用 GWAS 基因分型筛选可能与特发性 SPGF 病例有关的常见和罕见变异的益处，无论这些病例是由复杂病因还是单基因病因引起的。发现SPGF的新型遗传风险因素并阐明其潜在的遗传原因，为个性化医疗和生殖咨询提供了新的视角：这项工作得到了西班牙科学与创新部通过西班牙国家科技研究与创新计划（PID2020-120157RB-I00）以及安达卢西亚政府通过 "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)"（编号PY20_00212）和 "Proyectos de Investigación aplicada FEDER-UGR 2023"（编号C-CTS-273-UGR23）研究项目提供的支持。S.G.-M.获得了上述项目（参考编号PY20_00212和PID2020-120157RB-I00）的资助。A.G.-J.得到了 MCIN/AEI/10.13039/501100011033 和 FSE "El FSE invierte en tu futuro"（资助编号：FPU20/02926）的资助。IPATIMUP 整合了 i3S 研究小组，该小组由葡萄牙科技基金会（FCT）提供部分支持，由欧洲社会基金（COMPETE-FEDER）和国家基金（项目 PEstC/SAU/LA0003/2013 和 POCI-01-0145-FEDER-007274）资助。S.S. 由 FCT 基金资助（10. 54499/DL57/2016/CP1363/CT0019）、ToxOmics-毒物基因组学和人类健康、遗传学、肿瘤学和人类毒理学中心的支持，并得到葡萄牙科技基金会（UIDP/00009/2020 和 UIDB/00009/2020）的部分支持。S. Larriba 得到了卡洛斯三世健康研究所（资助：DTS18/00101）（由 FEDER 基金/欧洲地区发展基金（ERDF）--建设欧洲的一种方式共同资助）和加泰罗尼亚自治区（Generalitat de Catalunya）（资助：2021SGR052）的支持。S. Larriba 还得到了 SNS-Dpt.CES09/020）。所有作者声明与本研究无利益冲突。
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引用次数: 0
Reply: Birth rate decline, COVID-19 pandemic, and vaccination programmes. 答复：出生率下降、COVID-19 大流行和疫苗接种计划。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae068
Tomáš Sobotka, Maria Winkler-Dworak, Kryštof Zeman
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引用次数: 0
Birth rate decline, COVID-19 pandemic, and vaccination programmes. 出生率下降、COVID-19 大流行和疫苗接种计划。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae067
Hinpetch Daungsupawong, Viroj Wiwanitkit
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引用次数: 0
Lab-based semen parameters as predictors of long-term health in men-a systematic review. 基于实验室的精液参数作为男性长期健康的预测指标--系统综述。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae066
Silvia Nedelcu, Srisailesh Vitthala, Abha Maheshwari
<p><strong>Study question: </strong>Can semen parameters predict long-term health outcomes in men?</p><p><strong>Summary answer: </strong>There is a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration.</p><p><strong>What is known already: </strong>Male infertility has been long associated with a higher mortality risk and possibly higher chance of developing comorbidities but there has been less focus on semen analysis as a potential predictive factor.</p><p><strong>Study design size duration: </strong>We searched PubMed/MEDLINE, EMBASE, and EBM databases from inception to December 2023. MESH term strategy: heading 1 ('OR', semen analysis, sperm count, sperm parameter*, male infertility, azoospermia, aspermia, oligospermia, teratozoospermia, asthenozoospermia) 'AND' heading 2 ('OR', morbidity, mortality, diabetes, cancer, cardiovascular, death, hypertension, stroke, long-term health). We included all studies that analyzed the risk of mortality and/or future development of comorbidities in men with at least one semen analysis. Case series and reviews were excluded.</p><p><strong>Participants/materials setting methods: </strong>A narrative synthesis was done for all studies and meta-analysis where possible. Odds ratio (ORs) (95% CI, <i>P</i>-value) were calculated for all men with one suboptimal semen parameter and associated with the risk of a particular outcome. The risk of bias was assessed with QUADAS-2.</p><p><strong>Main results and the role of chance: </strong>Twenty-one studies were finally included. There was either a high or unclear risk of bias in all studies. The results only allowed for meta-analysis on categories of sperm concentration. We found a 2-fold increase in mortality risk in azoospermic men compared to oligospermic (OR 1.96, 95% CI: 1.29-2.96) and normozoospermic (OR 2.00, 95% CI: 1.23-3.25) groups, but not in oligospermic compared to normozoospermic (OR 1.04, 95% CI: 0.52-2.09). There was no difference in risk of cardiovascular disease in any of the sperm concentration groups (azoospermic-oligospermic OR 0.94, 95% CI: 0.74-1.20, azoospermic-normozoospermic OR 1.11, 95% CI: 0.71-1.75, and oligospermic-normozoospermic OR 1.12, 95% CI: 0.80-1.55). OR for diabetes in azoospermic men was higher only compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01). The risk of all-site cancer was higher in azoospermic men compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01) and normozoospermic (OR 2.18, 95% CI: 1.20-3.96). Only azoospermic men might be at higher risk of testicular cancer when compared to men with normal sperm concentration (OR 1.80, 95% CI: 1.12-2.89).</p><p><strong>Limitations reasons for caution: </strong>Although our pooled analysis shows an increased risk of mortality and all-site cancer risk in azoospermic men, the results show a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Given the limited available data, the nature of the
研究问题精液参数能否预测男性的长期健康状况？目前尚无证据表明精液浓度低的男性患合并症的风险更高：男性不育长期以来一直与较高的死亡风险和可能较高的合并症发病几率相关，但精液分析作为潜在的预测因素却较少受到关注：我们检索了从开始到 2023 年 12 月的 PubMed/MEDLINE、EMBASE 和 EBM 数据库。MESH术语策略：标题1（'OR'，精液分析，精子数量，精子参数*，男性不育，无精子症，无精症，少精子症，畸形精子症，无精子症）'和'标题2（'OR'，发病率，死亡率，糖尿病，癌症，心血管，死亡，高血压，中风，长期健康）。我们纳入了所有分析男性死亡风险和/或未来合并症发展的研究，其中至少有一项精液分析。参与者/材料设置方法：对所有研究进行叙述性综合，并在可能的情况下进行荟萃分析。计算了所有精液参数不达标的男性与特定结果风险的比值比（ORs）（95% CI，P 值）。用 QUADAS-2 评估了偏倚风险：最终纳入了 21 项研究。所有研究的偏倚风险都很高或不明确。结果只允许对精子浓度类别进行荟萃分析。我们发现，与少精子男性（OR 1.96，95% CI：1.29-2.96）和正常无精子男性（OR 2.00，95% CI：1.23-3.25）相比，无精子男性的死亡风险增加了 2 倍，但与正常无精子男性相比，少精子男性的死亡风险没有增加（OR 1.04，95% CI：0.52-2.09）。任何精子浓度组的心血管疾病风险均无差异（无精子-少精子 OR 0.94，95% CI：0.74-1.20；无精子-无精子 OR 1.11，95% CI：0.71-1.75；少精子-无精子 OR 1.12，95% CI：0.80-1.55）。无精症男性患糖尿病的 OR 值仅高于少精症男性（OR 值为 2.16，95% CI：1.55-3.01）。与少精子男性（OR 2.16，95% CI：1.55-3.01）和正常无精子男性（OR 2.18，95% CI：1.20-3.96）相比，无精子男性罹患全部位癌症的风险更高。与精子浓度正常的男性相比，只有无精症男性患睾丸癌的风险可能更高（OR 1.80，95% CI：1.12-2.89）：尽管我们的汇总分析显示无精症男性的死亡风险和罹患全部位癌症的风险增加，但结果显示缺乏证据表明精液浓度低的男性罹患合并症的风险更高。鉴于可用数据有限、研究性质和偏倚风险较高，应谨慎解释这些结果：目前还没有足够的数据来证实精液分析作为男性长期健康状况不良预测指标的可用性，尤其是在普通人群中：本研究未获得任何资助。A.M.曾接受默克雪兰诺、Ferring、Gedeon Richter、Pharmasure和Cook Medical的资助参加医学会议；曾是Ferring顾问委员会的成员；曾应邀为默克雪兰诺顾问委员会做讲座。S.N. 曾获得 Ferring 和 Cook Medical 提供的参加医学会议的资助：PROSPERO 编号：CRD42024507563。
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引用次数: 0
Membrane-bound receptor for advanced glycation end products (RAGE) is a stable biomarker of low-quality sperm. 膜结合的高级糖化终产物受体（RAGE）是低质量精子的稳定生物标志物。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae064
Jill Browning, Magda Ghanim, William Jagoe, Jennifer Cullinane, Louise E Glover, Mary Wingfield, Vincent P Kelly

Study question: Does receptor for advanced glycation end products (RAGE) on the surface membrane of the sperm cell function as a biomarker of low-quality sperm?

Summary answer: Membrane-bound RAGE at a cellular level directly correlates with low sperm motility, high cell permeability, decreased mitochondrial function, DNA fragmentation, and higher levels of apoptosis.

What is known already: RAGE has previously been measured by ELISA in low-quality sperm in diabetic men and has been shown to correlate with DNA fragmentation (terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay).

Study design size duration: Semen samples were recovered from 60 non-obese, non-diabetic and non-smoking subjects, washed with fresh media, and analysed directly or purified further by differential gradient centrifugation (DGC) or fractionated by direct swim-up before being analysed for sperm motility and molecular health parameters, including cell membrane permeability, cell death, mitochondrial membrane potential, DNA fragmentation, and RAGE protein expression.

Participants/materials setting methods: Sperm motility assessments were carried out by computer-assisted sperm analysis (CASA) on 1000 spermatozoa for washed samples and 300 spermatozoa for purified samples. Molecular sperm health parameters were evaluated using flow cytometry with the use of the following markers: DAPI for cell membrane permeability, Annexin V/DAPI for cell death (apoptosis and necrosis), MitoTracker® Red CMXRos for mitochondrial membrane potential, TUNEL assay for DNA fragmentation and 8-hydroxy-2-deoxyguanosine for identification of oxidative damage to sperm DNA, and contrasted to membrane-bound RAGE expression levels, which were evaluated using an anti-RAGE monoclonal mouse antibody.

Main results and the role of chance: RAGE protein was shown to be present on the acrosomal and equatorial regions of sperm, with the levels of membrane bound receptor strongly correlating with poor sperm health across all parameters tested; motility (R 2 = 0.5441, P < 0.0001) and mitochondrial membrane potential (R 2 = 0.6181, P < 0.0001) being of particular note. The analysis was performed at a single cell level thereby removing confounding complications from soluble forms of the RAGE protein that can be found in seminal plasma. The expression of the RAGE protein was shown to be stable over time and its levels are therefore not subject to variation in sample handling or preparation time.

Large scale data: N/A.

Limitations reasons for caution: Inclusion criteria for this study were non-diabetic, non-obese and non-smoking participants to assess the distribution of RAGE expression in the general population, thereby excluding disease conditions that may inc

研究问题：精子细胞表面膜上的高级糖化终产物受体（RAGE）是否可作为低质量精子的生物标志物？在细胞水平上，膜结合的 RAGE 与精子活力低、细胞通透性高、线粒体功能下降、DNA 断裂和细胞凋亡水平升高直接相关：研究设计的规模和持续时间：从60名非肥胖、非糖尿病和非吸烟的受试者中采集精液样本，用新鲜培养基洗涤，直接分析或通过差分梯度离心法（DGC）进一步纯化，或通过直接泳升法分馏，然后分析精子活力和分子健康参数，包括细胞膜通透性、细胞死亡、线粒体膜电位、DNA碎片和RAGE蛋白表达：精子活力评估采用计算机辅助精子分析法（CASA）进行，水洗样本的精子数量为 1000 个，纯化样本的精子数量为 300 个。分子精子健康参数采用流式细胞术进行评估，并使用以下标记物：DAPI 检测细胞膜通透性，Annexin V/DAPI 检测细胞死亡（凋亡和坏死），MitoTracker® Red CMXRos 检测线粒体膜电位，TUNEL 检测 DNA 断裂，8-hydroxy-2-deoxyguanosine 检测精子 DNA 氧化损伤，并与膜结合 RAGE 表达水平进行对比，后者使用抗 RAGE 单克隆小鼠抗体进行评估：主要结果和偶然因素：RAGE 蛋白存在于精子的顶体和赤道区域，膜结合受体的水平与精子在所有测试参数中的健康状况密切相关；活力（R 2 = 0.5441，P R 2 = 0.6181，P 大比例数据：不适用：本研究的纳入标准是非糖尿病、非肥胖和非吸烟的参与者，以评估普通人群中 RAGE 表达的分布情况，从而排除可能增加精子中 RAGE 表达或导致精子质量低下的疾病。该研究并未涉及与男性不育症相关的其他患者亚群或疾病状态对 RAGE 表达的影响。流式细胞术精子分析法不适于研究精子数量少的男性：该研究结果表明，RAGE表达是精子细胞健康的分子标志物，可通过清除RAGE表达的精子改善辅助生殖，并通过将其作为男性不育症的生物标志物促进不明原因不育症的诊断：该研究由爱尔兰研究委员会根据爱尔兰政府计划（GOIPG/2015/3729）和爱尔兰企业创新合作伙伴计划（IP-2020-0952）资助。所有作者声明不存在利益冲突。
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引用次数: 0
Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43 972 women. 妇女可能无法从重复冷冻胚胎移植中获益：对 43 972 名妇女的累积活产率进行的回顾性分析。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-10-28 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae063
Yuqi Zeng, Yali Liu, Yunhan Nie, Xi Shen, Tiantian Wang, Yanping Kuang, Li Wang
<p><strong>Study question: </strong>Which specific groups of women would not benefit from repeated frozen embryo transfers (FETs)?</p><p><strong>Summary answer: </strong>Women over 45 years of age should stop treatment after three FET attempts due to the absence of further benefits, while women aged 40-45 years and those with a diminished ovarian reserve and other causes of infertility have a lower chance of improving their cumulative live birth rate (CLBR) within five FET cycles and experience fewer advantages from repeated transfers.</p><p><strong>What is known already: </strong>In real-life scenarios of ART, women who fail to achieve a live birth often choose to undergo repeated FETs via the freeze-all strategy.</p><p><strong>Study design size duration: </strong>This retrospective study included 43 972 women who underwent 86 496 oocyte retrieval cycles and 82 022 FET cycles between January 2010 and March 2023 under the freeze-all strategy.</p><p><strong>Participants/materials setting methods: </strong>We categorized the population based on the female's age at the first oocyte pick-up (OPU) cycle (Groups 1-6: <30, 30-34, 35-39, 40-42, 43-44, and ≥45 years of age), number of retrieved oocytes at the first OPU cycle (Groups 1-5: 1-5, 6-10, 11-15, 16-20, and >20 oocytes), and causes of infertility (Groups 1-9: tubal factor, male factor, polycystic ovary syndrome, diminished ovarian reserve, endometriosis, other uterine factors, combined factors, unexplained infertility, and other infertility) to analyse their CLBRs within different FET cycles via Kaplan-Meier analysis (optimistic method) and the competing risk method (conservative method). We utilized multivariate Cox and Fine-Gray models to examine the associations between the CLBR and age, the number of retrieved oocytes, and nine causes of infertility.</p><p><strong>Main results and the role of chance: </strong>The CLBR decreased with increasing female age over five FET cycles (Groups 1-6: optimistic method: 96.4%, 94.2%, 86.0%, 50.2%, 23.1%, and 10.1%; conservative method: 87.1%, 82.0%, 67.8%, 33.9%, 13.8%, and 3.5%, respectively). Moreover, there was an increasing trend in the number of retrieved oocytes (Groups 1-5: optimistic method: 82.5%, 91.7%, 93.6%, 94.1%, and 96.2%; conservative method: 58.6%, 76.7%, 84.8%, 88.0%, and 92.5%, respectively). Furthermore, the CLBR varied across different causes of infertility (Groups 1-9: optimistic method: 91.7%, 93.1%, 96.6%, 79.2%, 89.9%, 76.1%, 90.0%, 92.9%, and 35.4%; conservative method: 77.3%, 79.4%, 88.9%, 46.7%, 72.7%, 62.1%, 74.4%, 78.8%, and 20.1%, respectively).</p><p><strong>Limitations reasons for caution: </strong>Calculating the actual CLBR for each person is difficult because some patients have remaining embryos that have not been transferred; additionally, the current statistical methodology uses both optimistic and conservative methods to calculate the CLBR, and in real life, the CLBR falls between the optimistic and conservative curve
研究问题：哪些特定妇女群体不会从重复冷冻胚胎移植（FET）中获益？45岁以上的妇女在尝试三次冷冻胚胎移植后，由于没有进一步的益处，应停止治疗；而40-45岁的妇女以及卵巢储备功能减退和其他原因导致不孕的妇女，在五个冷冻胚胎移植周期内提高累积活产率（CLBR）的几率较低，重复移植的益处也较少：在抗逆转录病毒疗法的实际应用中，未能实现活产的妇女通常会选择通过全部冷冻策略进行重复FET：这项回顾性研究纳入了 43 972 名女性，她们在 2010 年 1 月至 2023 年 3 月期间接受了 86 496 个卵母细胞取回周期和 82 022 个 FET 周期，均采用了冻存策略：我们根据女性首次取卵（OPU）周期时的年龄（1-6 组：20 个卵母细胞）和不孕原因（1-9 组：输卵管因素、男性因素、多囊肾）对人群进行了分类：输卵管因素、男性因素、多囊卵巢综合征、卵巢储备功能减退、子宫内膜异位症、其他子宫因素、综合因素、不明原因不孕症和其他不孕症），通过卡普兰-梅耶分析法（乐观法）和竞争风险法（保守法）分析她们在不同 FET 周期内的 CLBR。我们利用多变量 Cox 和 Fine-Gray 模型研究了 CLBR 与年龄、取卵数量和九种不孕原因之间的关系：在五个 FET 周期中，CLBR 随女性年龄的增加而下降（1-6 组：乐观法：分别为 96.4%、94.2%、86.0%、50.2%、23.1% 和 10.1%；保守法：分别为 87.1%、82.0%、67.8%、33.9%、13.8% 和 3.5%）。此外，取回的卵母细胞数量呈上升趋势（1-5 组：乐观法：82.5%、91.7%、93.6%、94.1% 和 96.2%；保守法：58.6%、76.7%、94.1% 和 96.2%）：分别为 58.6%、76.7%、84.8%、88.0% 和 92.5%）。此外，CLBR 在不同的不孕原因中也存在差异（1-9 组：乐观法：91.7%、93.1%、96.6%、79.2%、89.9%、76.1%、90.0%、92.9% 和 35.4%；保守法：77.3%、79.4%、79.4%、88.0% 和 92.5%）：需要注意的局限性：计算每个人的实际CLBR很困难，因为有些患者还有剩余的胚胎没有移植；此外，目前的统计方法使用乐观和保守两种方法来计算CLBR，而在现实生活中，CLBR介于乐观和保守曲线之间：我们的研究首次确定了未能从重复FET中获益的特定妇女亚群，以及在移植不成功后需要合理中止治疗的妇女亚群：本研究得到了国家自然科学基金的资助（基金号：82271732-Y.S.）：82271732 给 Y.K.，82071603 给 L.W.，82001502 给 Y.L.，82201888 给 X.S.）。作者声明他们在本研究中没有利益冲突：不适用。
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引用次数: 0
Sperm and leukocyte telomere length are related to sperm quality parameters in healthy men from the Led-Fertyl study. Led-Fertyl研究中健康男性的精子和白细胞端粒长度与精子质量参数有关。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae062
María Fernández de la Puente, Cristina Valle-Hita, Albert Salas-Huetos, María Ángeles Martínez, Elena Sánchez-Resino, Silvia Canudas, Daniel Torres-Oteros, Joana Relat, Nancy Babio, Jordi Salas-Salvadó

Study question: Could sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?

Summary answer: A positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated.

What is known already: Male factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited.

Study design size duration: A total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.

Participants/materials setting methods: TLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA® system according to the World Health Organization (WHO) 2010 guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders.

Main results and the role of chance: Participants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (β: 1.09; 95% CI: 0.09-2.09 and β: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; P-trend < 0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (β: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; P-trend < 0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (β: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; P-trend = 0.004), and total count (β: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; P-trend < 0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables.

Limitations reasons for caution: One limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large.

Wider implications of the findings: Sperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications.

研究问题精子和白细胞端粒长度（TL）与普通人群中男性的精子质量参数和生殖健康是否相关？已证实精子和白细胞端粒长度与精子浓度和总计数呈正相关：男性因素几乎占夫妇不育症病例的一半，在精子参数受损的男性精子中观察到较短的TL。然而，来自普通人群的男性的证据却很有限：在 2021 年 2 月至 2023 年 4 月期间，共招募了 200 名育龄志愿者参与精液图和其他男性生育能力相关参数的生活方式和环境决定因素（Led-Fertyl）横断面研究：使用定量聚合酶链反应（qPCR）分别测量了 168 名和 194 名参与者精子和白细胞中的 TLs。根据世界卫生组织（WHO）2010 年指南，使用计算机辅助精子分析（CASA）SCA® 系统分析精子参数，包括浓度、总计数、活力、生命力和形态。在对潜在混杂因素进行调整后，采用多变量回归模型评估精子和白细胞TL（以三等分或连续变量表示）与精子质量参数之间的关系：主要结果和偶然性的作用：精子TL为2分层（T2）和3分层（T3）的参与者精子浓度较高（β：1.09; 95% CI: 0.09-2.09 和 β: 2.06; 95% CI: 1.04-3.09; P-trend P-trend P-trend = 0.004）和总计数（β：3.49; 95% CI: 1.62-5.35 for T3 vs T1; P-trend 局限性 需谨慎的原因：局限性之一是横断面研究设计无法确定因果关系。此外，该研究的样本量也不能算大：研究结果的广泛意义：在普通人群中，精子和白细胞TL与精子质量参数有关。需要进行更多的测定和样本量更大的进一步研究，以明确这些关联的机制，并探讨进一步的影响：Led-Fertyl研究得到了西班牙政府生物医学研究官方资助机构卡洛斯三世健康研究所（ISCIII）通过健康研究基金（FIS）提供的支持，并由欧盟ERDF/ESF "创造欧洲的方式"/"投资你的未来"（PI21/01447）和塔拉戈纳省议会（2021/11-No.Exp. 8004330008-2021-0022642）共同资助。J.S.-S.是本研究的第一作者，他的部分研究经费由 ICREA 学术项目提供。M.F.d.l.P. 获得了 Rovira i Virgili 大学和塔拉戈纳省议会的博士前期资助（2020-PMF-PIPF-8）。C.V.-H.获得了加泰罗尼亚自治区政府（2022 FI_B100108）的博士前期资助。M.Á.M. 获得了 Sara Borrell 博士后奖学金（CD21/00045-Instituto de Salud Carlos III (ISCIII)）。所有作者声明不存在利益冲突：不适用。
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引用次数: 0
Reply: Emerging evidence of endometrial compaction in predicting ART outcomes. 回复：子宫内膜压实在预测抗逆转录病毒疗法结果方面的新证据。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-10-11 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae061
Hannan Al-Lamee, Gayathri Delanerolle, Dharani K Hapangama, Nicola Tempest
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引用次数: 0
Emerging evidence of endometrial compaction in predicting ART outcomes. 子宫内膜压实在预测抗逆转录病毒疗法结果方面的新证据。
IF 8.3 Q1 OBSTETRICS & GYNECOLOGY
Human reproduction open
Pub Date : 2024-10-10 eCollection Date: 2024-01-01 DOI: 10.1093/hropen/hoae060
Guangyao Lin, Stella Lim Jin Yie, Lianwei Xu
{"title":"Emerging evidence of endometrial compaction in predicting ART outcomes.","authors":"Guangyao Lin, Stella Lim Jin Yie, Lianwei Xu","doi":"10.1093/hropen/hoae060","DOIUrl":"10.1093/hropen/hoae060","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae060"},"PeriodicalIF":8.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514159","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
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